Association of possible sleep bruxism in children with different chronotype profiles and sleep characteristics.
Sleep bruxism (SB) in children has been associated with several sleep characteristics, which may alter their sleep pattern. This change affects the internal biological clock and consequently the chronotype profile. The aim of this study was to evaluate the existence of an association between possible SB in children with specific chronotype profiles and sleep characteristics. The study included 207 parents/guardians of children aged between 3 and 12 years who were waiting for their children's dental treatment at the Pediatric Dentistry Clinic of the Federal University of Rio de Janeiro, Brazil. A questionnaire on the socio-demographic characteristics of parents and children as well as on the features of the children's sleep was applied. In addition, the CIRENS scale (Circadian Energy Scale) was completed by the parents to identify the children's chronotype. A chi-squared test was used to determine the association between possible SB, the chronotype, and sleep characteristics. A multiple logistic regression model was implemented to observe the influence of chronotype, age, and other independent variables on the possible SB. The logistic regression model demonstrated that nocturnal agitation (p = 0.009; OR = 3.42) and nightmares (p = 0.045; OR = 3.24) were associated with possible SB in children. Although no significant association (p = 0 .089) between the chronotype profile and possible SB was observed in the 3 to 5 years age group, a proportional difference was observed between the chronotype categories in this age group-12.5% of children with SB had a morning type, while 26.4% had an intermediate type and 47.8% an evening type compared to those without possible SB. Nocturnal agitation and nightmares were associated with possible SB. In addition, young children with an evening chronotype had a tendency toward possible SB.


Physical preparation of alginate/chitosan polyelectrolyte complexes for biomedical applications.
Polyelectrolyte complexes represent a special class of polymeric compounds consisting of stoichiometric equivalents of oppositely charged polyions interacting together spontaneously to yield a complex in different forms. The present study aimed at preparing coacervates of alginate and chitosan polymers ready for casting as wound dressing films. This was based on controlling the pH of solutions and the reactions speed through controlling the rate of mixing of the polymers solutions together without using any water-miscible solvents. Alginate was modified with radiation and oxidation, and the interactions of the resulting chains and chitosan chains were tested with FTIR spectroscopy and scanning of the resulting films with SEM. This work showed the ability to prepare a complex of highly connected polymeric chains for further biomedical applications. This complex in the form of hydrogel could enhance the proliferation of cells in vitro and the healing efficiency with accelerating the wound closure rate as evidenced through the histological observations.


Improved chilling tolerance in glasshouse-grown potted sweet basil by end-of-production, short-duration supplementary far red light.
Sweet basil is a popular culinary herb used in many cuisines around the world and is widely grown commercially for retail as a live potted plant. However, basil is easily damaged by temperatures below 12 °C meaning plants must be transported from the grower to the retailer in a warm transport chain, adding considerable commercial cost in temperate countries. Improvement of chilling tolerance has been demonstrated in post-harvest crops such as tomato fruits and, indeed, fresh cut basil, by manipulation of the red:far red ratio of light provided to plants throughout the photoperiod and for a significant duration of the growing process in controlled environment chambers. We tested the effectiveness of periodic short-duration end-of-production supplementary far red light treatments designed for use with basil plants grown in a large scale commercial glasshouse for the live potted basil market. Four days of periodic, midday supplementary far red light given at end of production induced robust tolerance to 24 h of 4 °C cold treatment, resulting in greatly reduced visual damage, and reduced physiological markers of chilling injury including electrolyte leakage and reactive oxygen species accumulation. Antioxidant levels were also maintained at higher levels in live potted basil following this cold treatment. RNAseq-based analysis of gene expression changes associated with this response pointed to increased conversion of starch to soluble raffinose family oligosaccharide sugars; increased biosynthesis of anthocyanins and selected amino acids; inactivation of gibberellin signaling; and reduced expression of fatty acid desaturases, all previously associated with increased chilling tolerance in plants. Our findings offer an efficient, non-invasive approach to induce chilling tolerance in potted basil which is suitable for application in a large-scale commercial glasshouse.


Towards commercial production of microbial surfactants.
Biosurfactants or microbial surfactants are surface-active biomolecules that are produced by a variety of microorganisms. Biosurfactants have gained importance in the fields of enhanced oil recovery, environmental bioremediation, food processing and pharmaceuticals owing to their unique properties--higher biodegradability, lower toxicity, and effectiveness at extremes of temperature, pH and salinity. However, large-scale production of these molecules has not been realized because of low yields in production processes and high recovery and purification costs. This article describes some practical approaches that have been adopted to make the biosurfactant production process economically attractive: these include the use of cheaper raw materials, optimized and efficient bioprocesses and overproducing mutant and recombinant strains for obtaining maximum productivity. The application of these strategies in biosurfactant production processes, particularly those using hyper-producing recombinant strains in the optimally controlled environment of a bioreactor, might lead towards the successful commercial production of these valuable and versatile biomolecules in near future.


Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review.
The generation and function of immuno-suppressive regulatory T lymphocytes (Treg), which can differentiate in the thymus (tTreg) or in the periphery (pTreg), are regulated in an age-dependent manner. tTreg are produced at high levels in the first weeks of age, when they expand and colonize secondary lymphoid organs and peripheral tissues to protect the organism from autoimmune diseases and to promote tissue repair. Once this population of Treg is operational in the periphery, at puberty, thymic output of Treg declines, but self-reactive tTreg generated early on in life are maintained over time and play a major role in preserving homeostasis of the immune system. Extra-thymic pTreg differentiation declines later on in life. pTreg generated throughout life mainly protect the organism from chronic inflammation and the semi-allogeneic fetus from rejection. In this review, age-dependent modulation of the production and function of these two populations of Treg is described.


Light Chain-Restricted Plasmacytoid Cells in Hyperplastic Germinal CentersA Clinicopathologic Investigation.
Follicular hyperplasias (FHs) with light chain-restricted (LCR) plasmacytoid/plasma cells (PCs) within germinal centers (GCs) based on immunohistochemistry (IHC)/in situ hybridization (ISH) can potentially lead to diagnostic error. This study aims to better characterize such cases, including their clinical implications. LC expression by IHC/ISH was quantitatively assessed in GCs of 17 FHs with LCRGCs. BCL2, CD10, BCL6, BCL2, immunoglobulin (Ig) heavy chains, IgG4, and Epstein-Barr encoding region stains were performed. In total, 8 cases had polymerase chain reaction (PCR)-based clonality studies. All cases showed FH, including 4 with progressively transformed GCs (PTGCs); 0.8% to 52% (median, 21%) of the GCs were LCR; 13 of 17 had both κ- and λ-LCRGCs, and 4 of 17 had only κ-LCRGCs; 7 of 16 had prominent intrafollicular IgG4-positive cells. One case demonstrated BCL2-positive cells in focal LCRGCs but lacked BCL2 rearrangement. B-cell monoclonality was demonstrated in 3 of 8 cases (only after microdissection). Seven patients had autoimmune disorders, and 1 had had a transplant. Three patients had a history of lymphoma, 1 developed lymphoma, and 1 developed lymphomatoid granulomatosis subsequently. FHs with LCRGC by IHC/ISH are typically not associated with the development of lymphoma, even though they can express BCL2 and show monoclonality by PCR. They may be associated with increased intrafollicular IgG4-positive cells, PTGC, and autoimmunity.


Special Focus on Stage IV Cervical Cancer Patients: A Decade Experience.
The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stage IVA) and metastatic CC (i.e., stage IVB). A retrospective review was conducted based on all consecutive patients treatedfor stage IV CC in a comprehensive cancer care centre between 2004 and 2017. Sixty-eight patients were included. Performance status (PS) was ≥2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph node metastases (38.6%), 13 had only distant metastases (29.5%), and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n = 14, 58.3%) +/- concomitant chemotherapy, or a palliative treatment (n = 10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), 11 a primary concomitant chemoradiation (25%), and 10 a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stage IVA (95% CI = 0.7-33.9), and 10.5% for stage IVB (95% CI = 3.7-29.7). In multivariate analysis, PS >1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS >1 and pelvic lymph node involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC. In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.


The relationship between previous fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection.
The relationship between prior fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance was associated with any prior fluoroquinolone use over the previous 10 years and with the total number of fluoroquinolone courses prescribed (P<.001).


Substrate inhibition of transglucosyl-amylase by maltose.
Transglucosyl-amylase was inhibited by maltose when maltose served as a substrate. As a function of substrate concentration, the rates initially rose proportionately with increases of maltose levels until a maximal rate was attained. Further increases of maltose concentration decreased reaction rates. The attainment of a maximal rate with increasing substrate concentration and close correspondence between experimental and calculated rates indicated the involvement of ternary complex formation. Evidence also suggested that substrate inhibition is caused by maltose competing with water for the acceptor sites during complex formation.


What is the optimum duration of an asynchronous distance learning course?
An online, lecture/laboratory course in Human Physiology was run in two sections in five consecutive summers. In each year, the two sections were identical in content, assignments, and assessments but were different in duration; the shorter section was 1 mo and the longer section lasted 2 mo. The shorter section had a higher enrollment and a higher attrition rate. A postcourse survey revealed that the majority of the students in the shorter course believed that they would have spent more time studying and would have received a better grade had they taken the longer class. Interestingly, in any one year, there was no significant difference between the mean final grades earned by students in the two sections and by males and females. All students who completed the longer section and the majority of students in the shorter section of the course stated that they would recommend the longer class to a friend who was committed to taking this online course.


Alim Abdurahman.
"I would have liked to have discovered organic materials with superconductivity and room-temperature ferromagnetism … The biggest challenge facing scientists is narrowing the gap between the ideal and reality." Find out more about Alim Abdurahman in his Introducing … Profile.


The Neurotropic Varicella Zoster Virus: a Case of Isolated Abducens Nerve Palsy without Skin Rash in a Young Healthy Woman.
Varicella Zoster Virus (VZV) is a neurotropic virus whose reactivation can affect the central nervous system (CNS) and manifest as different neurological syndromes usually with dermatological involvement. Extraocular muscle palsies are not commonly described associated with VZV and their presence in the absence of a typical zoster rash is even rarer. Case report of a young immunocompetent patient with unilateral abducens nerve palsy, as an isolated manifestation of VZV infection. A 25-year-old healthy female presented to the emergency department with a subacute onset of painless horizontal binocular diploplia, over a month. Ophthalmological and neurological examination revealed an isolated right abducens nerve palsy, and polymerase chain reaction of the cerebrospinal fluid identified a VZV infection. There was no skin rash involvement. Other infectious, inflammatory, and autoimmune diseases were excluded. Treatment with intravenous acyclovir and dexamethasone improved but not completely resolved the diplopia and strabismus. The patient was submitted to a medial rectus recession surgery. VZV manifestations in the CNS can occur in healthy young individuals and can manifest in the absence of the typical skin rash. Isolated sixth nerve palsy is a very rare manifestation of VZV infection. Young patients with isolated ocular motor mononeuropathies, even with cardiovascular risk factors, benefit from a CNS-based approach and MRI and lumbar puncture should be considered. Reports show that extraocular muscle palsy associated with VZV is a transient condition and resolve partially or completely after few weeks.


Putative interhelical interactions within the PheP protein revealed by second-site suppressor analysis.
Highly conserved glycine residues within span I and span II of the phenylalanine and tyrosine transporter PheP were shown to be important for the function of the wild-type protein. Replacement by amino acids with increasing side chain volume led to progressive loss of transport activity. Second-site suppression studies performed with a number of the primary mutants revealed a tight packing arrangement between spans I and II that is important for function and an additional interaction between spans I and III. We also postulate that a third motif, GXXIG, present in span I and highly conserved within different members of the amino acid-polyamine-organocation family, may function as a dimerization motif. Surprisingly, other highly conserved residues, such as Y60 and L41, could be replaced by various residues with no apparent loss of activity.


Visualization and modelling of STLmax topographic brain activity maps.
This paper evaluates the descriptive power of brain topography based on a dynamical parameter, the Short-Term Maximum Lyapunov Exponent (STLmax), estimated from EEG, for finding out a relationship of STLmax spatial distribution with the onset zone and with the mechanisms leading to epileptic seizures. Our preliminary work showed that visual assessment of STLmax topography exhibited a link with the location of seizure onset zone. The objective of the present work is to model the spatial distribution of STLmax in order to automatically extract these features from the maps. One-hour preictal segments from four long-term continuous EEG recordings (two scalp and two intracranial) were processed and the corresponding STLmax profiles were estimated. The spatial STLmax maps were modelled by a combination of two Gaussians functions. The parameters of the fitted model allow automatic extraction of quantitative information about the spatial distribution of STLmax: the EEG signal recorded from the brain region where seizures originate exhibited low-STLmax levels, long before the seizure onset, in 3 out of 4 patients (1 out of 2 of scalp patients and 2 out of 2 in intracranial patients). Topographic maps extracted directly from the EEG power did not provide useful information about the location, therefore we conclude that the analysis so far carried out suggests the possibility of using a model of STLmax topography as a tool for monitoring the evolution of epileptic brain dynamics. In the future, a more elaborate approach will be investigated in order to improve the specificity of the method.


Erythrophagocytosis by segmented neutrophils in paroxysmal cold hemoglobinuria.
The authors report a case of paroxysmal cold hemoglobinuria (PCH) with pronounced erythrophagocytosis by segmented neutrophils. This type of erythrophagocytosis, though well-documented in vitro, is a rare phenomenon in vivo. A review of the literature shows an association between PCH and erythrophagocytosis by segmented neutrophils that the authors suggest may have diagnostic value.


Pancreatic Involvement in the Course of Inflammatory Bowel Disease in Children-A Multi-Center Study.
The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.


Assessment of dual inhibition property of newly discovered inhibitors against PCAF and GCN5 through in silico screening, molecular dynamics simulation and DFT approach.
p300/CBP-associated factor (PCAF) is one among the histone acetyltransferase (HAT) family enzymes. It is involved in the regulation of transcription by modifying the chromatin structure indirectly through the acetylation of histones. It has been emerged as a promising drug target for various types of cancer. A four-point pharmacophore with two hydrogen bond acceptor, one aromatic ring and one hydrophobic feature, was generated for six highly active isothiazolone derivatives as PCAF inhibitors in order to elucidate their anticancer activity. The generated pharmacophore was used for screening three different databases such as Maybridge, Life Chemicals and Chembridge databases. The screened compounds were further filtered through docking studies. Then the compounds were further carried for ADME prediction. The best three compounds BTB09406, F1418-0051 and F1880-1727 were docked to GCN5 to explore the dual inhibitory properties. The conformational stability of the protein-ligand complexes were analyzed through molecular dynamics simulation. Three best compounds were finally went through electronic structure analysis using density functional theory (DFT) at B3LYP/6-31**G level to understand their molecular reactivity. The results obtained from this study exploit that the three best compounds (BTB09406, F1418-0051 and F1880-1727) were found to have more potent and dual inhibitory properties.


Single wavelength colour tuning of spiropyran and dithienylethene based photochromic coatings.
Controlling the transmission of thin films with external stimuli is an important goal in functional optical materials and devices. Tuning is especially challenging where both broad band (neutral density filtering) and spectrally varied (colour) transmission are required. The external control provided by photochemically driven switching, between transmission levels and colours, is functionally simple from a device perspective. The limits due to the spectral ranges of individual photochromic compounds can be overcome by combining several photochromes within one material or device. Here we show that a combination of photochromic molecular switches immobilised in a PMMA polymer matrix enables tuning of colour and transparency. We show that only a single excitation wavelength is required through the use of the primary inner filter effect and the layered construction of the films in which the photochromes nitrospiropyran (NSP), and nitrothiospiropyran (TSP) or 1,2-bis-terthienyl-hexafluorocyclopentene (DTE) are separated spatially. The approach taken circumvents the need to match photochemical quantum yields and thermal reactivity of the component photochromes. The photochemical switching of the films was characterised by UV/vis absorption spectroscopy and shows that switching rates and photostationary states are limited by inner filter effects rather than the intrinsic properties of photochromes, such as photochemical quantum yields and thermal stability. The photochemical behaviour and stability of the photochromes in solution and in the PMMA films were compared and the concentration range over which self-inhibition of photochemical switching occurs was established. The rate of photochemical switching and the difference in transmission between the spiropyran and merocyanine forms in solution enable prediction of the performance in the films and enable rational design of colour tuning ranges and responsivity in thin film filters.


The nature of activatory and tolerogenic dendritic cell-derived signal II.
Dendritic cells (DCs) are central in maintaining the intricate balance between immunity and tolerance by orchestrating adaptive immune responses. Being the most potent antigen presenting cells, DCs are capable of educating naïve T cells into a wide variety of effector cells ranging from immunogenic CD4(+) T helper cells and cytotoxic CD8(+) T cells to tolerogenic regulatory T cells. This education is based on three fundamental signals. Signal I, which is mediated by antigen/major histocompatibility complexes binding to antigen-specific T cell receptors, guarantees antigen specificity. The co-stimulatory signal II, mediated by B7 family molecules, is crucial for the expansion of the antigen-specific T cells. The final step is T cell polarization by signal III, which is conveyed by DC-derived cytokines and determines the effector functions of the emerging T cell. Although co-stimulation is widely recognized to result from the engagement of T cell-derived CD28 with DC-expressed B7 molecules (CD80/CD86), other co-stimulatory pathways have been identified. These pathways can be divided into two groups based on their impact on primed T cells. Whereas pathways delivering activatory signals to T cells are termed co-stimulatory pathways, pathways delivering tolerogenic signals to T cells are termed co-inhibitory pathways. In this review, we discuss how the nature of DC-derived signal II determines the quality of ensuing T cell responses and eventually promoting either immunity or tolerance. A thorough understanding of this process is instrumental in determining the underlying mechanism of disorders demonstrating distorted immunity/tolerance balance, and would help innovating new therapeutic approaches for such disorders.


Self-limiting electrodeposition of hierarchical MnO₂ and M(OH)₂/MnO₂ nanofibril/nanowires: mechanism and supercapacitor properties.
Hierarchical nanostructures have generated great interest in the energy, materials, and chemical sciences due to the synergic properties of their composite architectures. Herein, a hierarchical MnO₂ nanofibril/nanowire array is successfully synthesized. The structure consists of a conformal layer of MnO₂ nanofibrils evenly distributed on the surface of the individual MnO₂ nanowires. The synthetic mechanism of this hierarchical structure is characterized by electrochemical measurements, Raman spectroscopy, EELS, and electron microscopy. This material was then investigated at slow scan rates for its charge storage mechanisms in different solvents. In aqueous electrolyte, the nanofibrils show a capacitance almost purely dedicated to double-layer and surface adsorption processes, while in an acetonitrile electrolyte, the nanofibrils' capacitance comes mainly from a cation insertion process. This material was also tested at high scan rates in aqueous solution for its practical supercapacitor capabilities. The material shows a large capacitance of 298 F/g at 50 mV/s and 174 F/g at 250 mV/s. It also maintains 85.2% of its capacitance after 1000 cycles. The material also displays easily controllable parameters such as nanowire length, nanowire diameter, and amount of nanofibril material which is shown here to affect the capacitance dramatically.


Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia.
Genetic aberrations involving the mixed lineage leukemia (MLL) gene are frequently diagnosed in infant acute lymphoblastic and acute myeloid leukemia. More than 60 fusion partner genes have been described at the molecular level, 31 of which have been characterized solely in infant leukemia cases. Here we describe a new MLL fusion partner gene, NEBL, which was identified in a case of acute myeloid leukemia in an infant. The chromosomal breakpoints of the MLL-NEBL and NEBL-MLL fusion genes were cloned by long-distance inverse polymerase chain reaction. The chromosomal breakpoints were located at 10p12, approximately 570 kb telomic of the MLLT10 (AF10) gene. AF10 and NEBL are localized in such close vicinity that they cannot be distinguished cytogenetically by G banding. Therefore, the combination of cytogenetic and independent molecular techniques such as long-distance inverse polymerase chain reaction are indispensable for the rapid identification and characterization of rare MLL rearrangements.


[Surgical chemoprophylaxis in the Emilia Romagna region].
The aim of this study is to assess the compliance with evidence based medicine of the practices of administration of perioperative surgical chemoprophylaxis in the Emilia Romagna region. Prospective study of 1 month duration including 31 of the 36 public hospital existing in the region. For all the patients admitted to one of the 121 participating units and undergoing a surgical operation, data were collected on the surgical prophylaxis administered, including type of antibiotic, time of administration and duration. Surgical prophylaxis was given in 4,946 surgical operations of the 6,167 included in the study. The median frequency of surgical prophylaxis administration was 81% ranging from 67% to 97% in different Local Health Authorities. Chemoprophylaxis was given also for surgical operations where, according to systematic literature reviews, the cost-benefit ratio is absolutely unfavourable to the use of antibiotics. In 2,120 cases (42.9%) the time of administration was not perioperative and, thus, differed from the recommended practice: in 264 cases (5%), antibiotics were administered after the operation. In 42.6% of the cases the duration of administration was not a short-term prophylaxis, being longer than 24 hours: in these 2,108 cases, the median duration was 4 days ranging form 1 to 90 days. In 48% of the cases cefazolin was administered; in 1,347 cases (23.4%), instead, a third or fourth generation cephalosporin was used. The survey pointed out an overuse of antibiotics, both for indications and duration, even when clear evidences of efficacy are lacking; moreover, the criteria for selection of specific antibiotics frequently did not take into account the risk of selecting antimicrobial resistance strains.


Activation of murine kupffer cells by administration with gel-forming (1-->3)-beta-D-glucan from Grifola frondosa.
The effect of gel-forming (1-->3)-beta-D-glucan on the immunological activities of murine kupffer cells was examined. A branched type gel-forming (1-->3)-beta-D-glucan, GRN, was administered intravenously to mice. GRN associating to kupffer cells was detected by an immunohistochemical technique using anti-GRN antibody. A kinetic study of the activation of kupffer cells revealed that GRN could induce the enhanced production of cytokines and nitric oxide on 4 to 7 d after the administration. The activities are further augmented by adding GRN in the culture. The cytostatic activity of kupffer cells against murine lymphoma, EL-4, was also augmented by a time course similar to nitric oxide production. The cytostatic activity was reduced by adding an inhibitor of nitric oxide synthase, implying that the cytostatic activity of kupffer cells to EL-4 was dependent on nitric oxide. The administration of GRN increased the expression of CD11b, known as a beta-glucan receptor, on kupffer cells at day 7. The above data suggest that GRN could activate murine kupffer cells to enhance the production of cytokines and nitric oxide, and that the activation required 4 or 7 d, at least, after the administration with GRN.


Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla.
The rostral ventrolateral medulla oblongata (RVLM) contains two functionally distinct types of neurons that control and orchestrate cardiovascular and respiratory responses to hypoxia and hypercapnia. One group is composed of the central chemoreceptor neurons of the retrotrapezoid nucleus, which provides a CO₂/H(+) -dependent drive to breathe and serves as an integration centre and a point of convergence of chemosensory information from other central and peripheral sites, including the carotid bodies. The second cluster of RVLM cells forms a population of neurons belonging to the C1 catecholaminergic group that controls sympathetic vasomotor tone in resting conditions and in conditions of hypoxia and hypercapnia. Recent evidence suggests that ATP-mediated purinergic signalling at the level of the RVLM co-ordinates cardiovascular and respiratory responses triggered by hypoxia and hypercapnia by activating retrotrapezoid nucleus and C1 neurons, respectively. The role of ATP-mediated signalling in the RVLM mechanisms of cardiovascular and respiratory activities is the main subject of this short review.


Analysis of Antibiotic Resistance Genes and its Associated SCCmec Types among Nasal Carriage of Methicillin Resistant Coagulase Negative Staphylococci from Community Settings, Chennai, Southern India.
The study was designed to find the distribution of SCCmec types and the various antibiotic resistance genes amongst MR-CoNS isolates from asymptomatic individuals. A total of 145 nasal swabs were collected from asymptomatic healthy individuals from community settings. Identification and speciation of CoNS were done by standard biochemical methods. Screening of methicillin resistance (mecA gene) and detection of various antibiotic resistant genes were done using multiplex PCR method. SCCmec types (I - V) were determined using multiplex PCR. 50 (44.6%) isolates were found to be methicillin resistant both by cefoxitin method and multiplex PCR. S. epidermidis (40%) was the predominant species followed by S. haemolyticus (28%), S. hominis (20%) and S. warneri (12%). Highest resistance was shown for cotrimoxazole (26%), followed by ciprofloxacin (24%), tetracycline (20%), erythromycin (18%), fusidic acid (10%) and mupirocin (6%). Among SCCmec types, 44 isolates showed single type, including type I (30%), type IV (24%), type II (18%), type V (14%) and type III (2%). 6 isolates showed two types, III+IV (n= 2), II+V (n=2), IV+V (n=1) and type I+V (n=1). In conclusion, to the best of our knowledge, this is the first study in India to study the distribution of antibiotic resistant genes and SCCmec types among MR-CoNS from community settings. This study highlights high prevalence of MR-CoNS in community and its role in harbouring genetically diverse SCCmec elements as antibiotic resistance determinant.


Pancreas divisum: magnetic resonance cholangiopancreatography findings.
Pancreas divisum is a common congenital abnormality of the pancreas that results from the lack of fusion between the dorsal and ventral pancreatic ducts during foetal development. In these cases, the dorsal duct becomes the main pancreatic duct and drains most of the pancreas. Pancreas divisum is mainly asymptomatic, but the prevalence of pancreas divisum is higher in patients with chronic abdominal pain and idiopathic pancreatitis. A study of 20 patients with pancreas divisum (12 men and eight women; aged 19-77 years; mean age 39 years) and who underwent magnetic resonance cholangiopancreatography (MRCP), was performed. In our series, pancreas divisum was clinically manifested as unexplained episodes of abdominal pain (mean duration 3.2 years) (60 percent), mild pancreatitis (30 percent) or incidentally (ten percent). MRCP demonstrated non-communicating dorsal and ventral ducts, independent drainage sites, a dominant dorsal pancreatic duct, and a small cystic dilatation of the dorsal duct at minor papilla (santorinocoele). In this pictorial essay, we review the most common MRCP features of pancreas divisum.


Pharmacotherapy of alcohol-withdrawal syndrome in hospitalised patients. Clinical and methodological aspects.
Because of the unreliability of the alcoholic, these suggestions are only intended for inpatients. Effective agents are presented first, and then the often very different pharmacological concepts are critically reviewed. Physicians use target symptoms as checkpoints for the effective pharmacological treatment of the alcohol-withdrawal syndrome. Clomethiazole and benzodiazepines are regarded as proven monotherapeutics against delirium. However, their somatic side effects and above all the problems of drug dependence make it necessary to look for a lower-risk medication. In every case, physicians must look more closely into the possibility of treating the individual alcohol-withdrawal syndrome with an agent less liable to cause addiction. Attractive, adequately tested alternatives are now becoming available for the large number of withdrawal syndromes which are below the level of delirium in terms of severity. This paper discusses the significance of substances without dependence potential, e.g. carbamazepine. This aspect is of special interest for the psychiatrist, whose task it is to guarantee the patient's abstinence after detoxification. We also look at other possible advantages of these substances when given in combination with drugs of the alcohol-barbiturate group against severe alcohol-withdrawal syndromes. Following a discussion of priority questions for further research, we draw attention to methodological deficiencies in earlier evaluation studies, and make suggestions for improved designs of drug trials.


Intrathecal Injection of Peripherally Mobilized Blood Stem Cells to Treat Multiple Sclerosis.
In this study, we analyzed 70 patients with worseningmultiple sclerosis despite pharmacologic treatment who were treated with several intrathecal injections of peripheral blood cells harvested by apheresis after granulocyte-colony stimulating factor treatment. Thirty-seven patients (52%) had a reduction of Expanded Disability Status Scale score; 10 patients had relapses, although these were milder than usual and more easily controlled by corticosteroids. Because mesenchymal cells increase in the peripheral blood after granulocyte-colony stimulating factor stimulation, a peripheral blood harvest seems easier and less costly than mesenchymal cell cultivation before injection. This seems to be a reasonable treatment for progressive multiple sclerosis.


Pathology of placenta in HIV infection.
The spectrum of HIV pathological lesions encountered in the placenta has not been well documented in the literature. To address this issue, we examined 51 placentae of HIV positive mothers, prospectively over a one year period and compared the pathology of the cases treated with zidovudine (AZT) or nevirapine (NVP) with untreated cases. We also correlated the placental pathology with the HIV status of the neonates. The maternal to child transmission rate was 4.44%. A lower fetal / placental weight ratio was seen in normal birth weight neonates compared to low birth weight neonates. No significant gross lesions were encountered and the placental disc did not show any significant decrease in dimensions. The commonest inflammatory lesion seen was chorio-amnionitis 31.37% and the commonest non-inflammatory lesion was cytotrophoblastic hyperplasia 76.47%. There was no significant decrease in the incidence of the lesions following anti-retroviral therapy in our study, and we did not find any correlation between the incidence of placental lesions and the HIV status of the newborn.


[Model for the response of radiographic films and implications for quality assurance].
The present paper describes the development of a model linking the optical density of a radiographic film to the applied dose. This model takes into account the kind of bremsstrahlung used in radiotherapy, and uses fewer parameters compared with the models developed so far. The measurements showed an influence of the field size on the model parameters. Monte Carlo simulations showed that different field sizes and depths in solid water can change the spectral distributions. The spectrum hardens with decreasing field size and increasing depth in phantom material. This has an influence on the model parameters. Nevertheless, the model can still be used to describe the relation between optical density and applied dose for films that are irradiated with fields of different size. A dose-rate dependence was not observed. The size and form of the fields used in calibration and application can therefore cause a systematic error in verification with film.


[Anti-VEGF therapy for diabetic retinopathy].
Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, its treatment involves specialists of different areas - endocrinologists, diabetes specialists, therapists, cardiologists, surgeons, anesthesiologists etc. For ophthalmologists the objective is to diagnose ocular pathological changes associated with diabetes mellitus, and to prescribe required treatment in a timely manner. Treatment methods used in DR can be divided into three main groups: laser coagulation of the retina, intravitreal injection of medications - inhibitors of the vascular endothelial growth factor (VEGF) and glucocorticoids, as well as surgical treatment. The present literature review addresses the use of anti-VEGF drugs in the therapy of DR, specifically the latest medications, the most important studies on the treatment of DR and diabetic macular edema (DME), as well as post hoc analysis of such studies, the role of these medications in the therapy of refractory DME and proliferative stage DR. The review also addresses the upcoming strategies for therapy, as well as the importance of medications in prevention of DR and DME.


The effects of contemporary redlining on the mental health of Black residents.
Understanding how structural racism, including institutionalized practices such as redlining, influence persistent inequities in health and neighborhood conditions is still emerging in urban health research. Such research often focuses on historical practices, giving the impression that such practices are a thing of the past. However, mortgage lending bias can be readily detected in contemporary datasets and is an active form of structural racism with implications for health and wellbeing. The objective of the current study was to test for associations among multiple measures of mental health and a measure of contemporary redlining. We linked a redlining index constructed using Home Mortgage Disclosure Act data (2007-2013) to 2021 health data for Black/African American participants in the Study of Active Neighborhoods in Detroit (n = 220 with address data). We used multilevel regression models to examine the relationship between redlining and a suite of mental health outcomes (perceived stress, anxiety, depressive symptoms, and satisfaction with life), accounting for covariates including racial composition of the neighborhood. We considered three mediating factors: perceived neighborhood cohesion, aesthetics, and discrimination. Although all participants lived in redlined neighborhoods compared to the complete Detroit Metropolitan area, participants with very low income, low levels of experienced discrimination, and lower perceptions of neighborhood aesthetics resided in highly redlined neighborhoods (score ≥5). We observed that higher resident-reported neighborhood aesthetics were found in neighborhoods with lower redlining scores and were associated with higher levels of satisfaction with life. We found that lower levels of redlining were significantly associated with higher levels of perceived discrimination, which was significantly, positively associated with anxiety, depressive symptoms, and perceived stress scores. Our findings highlight that contemporary redlining practices may influence the aesthetics of the built environment because these neighborhoods experience less investment, with implications for residents' satisfaction with life. However, areas with lower redlining may be areas where Black/African American people experience increased perceived discrimination.


Vascular endothelial profilin-1 drives a protumorigenic tumor microenvironment and tumor progression in renal cancer.
Overexpression of actin-binding protein profilin-1 (Pfn1) correlates with advanced disease features and adverse clinical outcome of patients with clear cell renal carcinoma, the most prevalent form of renal cancer. We previously reported that Pfn1 is predominantly overexpressed in tumor-associated vascular endothelial cells in human clear cell renal carcinoma. In this study, we combined in vivo strategies involving endothelial cell-specific depletion and overexpression of Pfn1 to demonstrate a role of vascular endothelial Pfn1 in promoting tumorigenicity and enabling progressive growth and metastasis of renal carcinoma cells in a syngeneic orthotopic mouse model of kidney cancer. We established an important role of endothelial Pfn1 in tumor angiogenesis and further identified endothelial Pfn1-dependent regulation of several pro- (VEGF, SERPINE1, CCL2) and anti-angiogenic factors (platelet factor 4) in vivo. Endothelial Pfn1 overexpression increases tumor infiltration by macrophages and concomitantly diminishes tumor infiltration by T cells including CD8+ T cells in vivo, correlating with the pattern of endothelial Pfn1-dependent changes in tumor abundance of several prominent immunomodulatory cytokines. These data were also corroborated by multiplexed quantitative immunohistochemistry and immune deconvolution analyses of RNA-seq data of clinical samples. Guided by Upstream Regulator Analysis of tumor transcriptome data, we further established endothelial Pfn1-induced Hif1α elevation and suppression of STAT1 activation. In conclusion, this study demonstrates for the first time a direct causal relationship between vascular endothelial Pfn1 dysregulation, immunosuppressive tumor microenvironment, and disease progression with mechanistic insights in kidney cancer. Our study also provides a conceptual basis for targeting Pfn1 for therapeutic benefit in kidney cancer.


Analysis of survival data with multiple causes of failure: a comparison of hazard- and logistic-regression models with application in demography.
"The purpose of the paper is to compare results of estimation and inference concerning covariate effects as obtained from two approaches to the analysis of survival data with multiple causes of failure. The first approach involves a dynamic model for the cause-specific hazard rate. The second is based on a static logistic regression model for the conditional probability of having had an event of interest. The influence of sociodemographic characteristics on the rate of family initiation and, more importantly, on the choice between marriage and cohabitation as a first union, is examined. We found that results, generally, are similar across the methods considered. Some issues in relation to censoring mechanisms and independence among causes of failure are discussed."


Ki67 and proliferation in breast cancer.
New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.


Use of Topical Corticosteroids in Dermatology: An Evidence-based Approach.
Topical corticosteroids (TCs) are the pillars of dermatotherapeutics. These drugs are the "magic molecules," provided they are used judiciously and appropriately, following a rational prescription. On exhaustive literature search in multiple databases, we found a significant evidence favoring the use of TCs in atopic eczema, localized vitiligo, psoriasis, chronic hand eczema, and localized bullous pemphigoid. However, contrary to conventional wisdom, we did not find any high-level scientific evidence in support of prescribing TCs in cutaneous lichen planus, sarcoidosis, and seborrhoeic dermatitis. Besides, evidence clearly advocates judicious use of mild-to-moderate corticosteroids (if required) in pregnancy and lactation and there is no risk of any fetal abnormality.


LcrQ and SycH function together at the Ysc type III secretion system in Yersinia pestis to impose a hierarchy of secretion.
LcrQ is a regulatory protein unique to Yersinia. Previous study in Yersinia pseudotuberculosis and Yersinia enterocolitica prompted the model in which LcrQ negatively regulates the expression of a set of virulence proteins called Yops, and its secretion upon activation of the Yop secretion (Ysc) type III secretion system permits full induction of Yops expression. In this study, we tested the hypothesis that LcrQ's effects on Yops expression might be indirect. Excess LcrQ was found to exert an inhibitory effect specifically at the level of Yops secretion, independent of production, and a normal inner Ysc gate protein LcrG was required for this activity. However, overexpression of LcrQ did not prevent YopH secretion, suggesting that LcrQ's effects at the Ysc discriminate among the Yops. We tested this idea by determining the effects of deletion or overexpression of LcrQ, YopH and their common chaperone SycH on early Yop secretion through the Ysc. Together, our findings indicated that LcrQ is not a negative regulator directly, but it acts in partnership with SycH at the Ysc gate to control the entry of a set of Ysc secretion substrates. A hierarchy of YopH secretion before YopE appears to be imposed by SycH in conjunction with both LcrQ and YopH. LcrQ and SycH in addition influenced the deployment of LcrV, a component of the Yops delivery mechanism. Accordingly, LcrQ appears to be a central player in determining the substrate specificity of the Ysc.


Hydrogen peroxide modulation of the superoxide anion production by stimulated neutrophils.
Hydrogen peroxide (H2O2) pretreatment of human neutrophils results in a suppression of the superoxide anion (O2) production in response to surface-acting stimulants such as lipopolysaccharide (LPS) and opsonized zymosan. This effect was not observed when phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) or tumor necrosis factor alpha (TNF alpha) were used as a stimuli. Since the response to PMA and other stimuli was unimpaired by preincubation with H2O2, we assume that the H2O2 modulated O2 production is probably due to alteration of the LPS receptor conformation rather than effecting directly NADPH-oxidase. The balance of reactive oxygen species (ROS) produced by neutrophils in the state of sepsis may thus be autoregulated by negative feedback phenomena of locally produced H202.


Sickle Cell Trait and the Risk of ESRD in Blacks.
Blacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to APOL1 high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait). Incident ESRD occurred in 40 of 739 (5.4%) individuals with SCT, six of 243 (2.5%) individuals with hemoglobin C trait, and 234 of 8927 (2.6%) noncarriers. The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT and 4.0 per 1000 person-years for noncarriers. Compared with individuals without SCT, individuals with SCT had a hazard ratio for ESRD of 2.03 (95% confidence interval, 1.44 to 2.84). Hemoglobin C trait did not associate with prevalent CKD or ESRD. The incidence rate for ESRD among participants with APOL1 high-risk genotypes was 6.6 per 1000 person-years, with a hazard ratio for ESRD of 1.77 (95% confidence interval, 1.31 to 2.38) for participants with, compared with those without, APOL1 high-risk genotypes. In this cohort, SCT strongly associated with risk of progression to ESRD in blacks, and this degree of risk for ESRD was similar to that conferred by APOL1 high-risk genotypes. These results may have important public policy implications for genetic counseling of SCT carriers.


Osseointegration enhanced by chemical etching of the titanium surface. A torque removal study in the rabbit.
Roughened implant surfaces are thought to enhance osseointegration. Torque removal forces have been used as a biomechanical measure of anchorage or osseointegration in which the greater forces required to remove implants may be interpreted as an increase in the strength of osseointegration. The purpose of this study was to compare the torque resistance to removal of screw shaped titanium implants having an acid etched (HC1/H2SO4) surface (Osseotite) with implants having a machined surface. Two custom screw shaped implants, 1 acid etched and the other machined, were placed into the distal femurs of 10 adult New Zealand White rabbits. These implants were 3.25 mm in diameter x 4.00 mm in length without holes, grooves or slots to resist rotation. Following a 2 month healing period, the implants were removed under reverse torque rotation with a digital torque measuring device. Two implants with the machined surface preparation failed to achieve osseointegration. All other implants were found to be anchored to bone. Resistance to torque removal was found to be 4 x greater for the implants with the acid etched surface as compared to the implants with the machined surface. The mean torque values were 20.50 +/- 6.59 N cm and 4.95 +/- 1.61 N cm for the acid etched and machined surfaces respectively. The results of this study suggest that chemical etching of the titanium implant surface significantly increases the strength of osseointegration as determined by resistance to reverse torque rotation.


Regulation of endothelial CD44 expression and endothelium-tumour cell interactions by hepatocyte growth factor/scatter factor.
Cancer metastasis involves the passage of tumour cells into and out of blood or lymphatic circulatory systems and requires their interaction with the endothelial cells lining these vessels. Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional protein that enhances tumour cell motility and extracellular matrix invasion and has been implicated as a mediator of metastasis. In this study, we have investigated the effect of HGF/SF on tumour cell-endothelial cell interactions. A fluorescent tumour cell-endothelial cell attachment assay demonstrated that, following endothelial monolayer stimulation with HGF/SF, tumour cell attachment to endothelium is increased. Addition of anti-CD44 antibodies in this assay inhibited the effects of HGF/SF. Western blotting studies showed that HGF/SF increased expression of the adhesion molecule CD44 in endothelial cells. These results were confirmed by both immunohistochemical staining and a cell-surface adhesion molecule ELISA. These results suggest that HGF/SF plays a key role in the initial adhesion mechanism between tumour cells and endothelial cells via up-regulation of CD44.


Flow injection chemiluminescence immunoassay of microcystin-LR by using PEI-modified magnetic beads as capturer and HRP-functionalized silica nanoparticles as signal amplifier.
A rapid sandwiched immunoassay of microcystin-LR (MC-LR) in water is proposed with flow injection chemiluminescence detection. The magnetic beads (MBs) were first modified with polyethyleneimine (PEI) by acylamide bond between the carboxyl group on the surface of MBs and the primary amine group in PEI, followed by immobilizing of anti-MC-LR (Ab1) onto PEI with glutaraldehyde as linkage. The resulting Ab1 modified MBs captured the target MC-LR in water, reacted with the horseradish peroxidase and anti-MC-LR co-immobilized silica nanoparticles, and were detected with flow injection chemiluminescence. When using PEI/MBs as the carrier of anti-MC-LR, the CL signal was greatly enhanced up to 9-fold compared to that using MBs without PEI modification. The CL signal was further amplified 13-fold when Si/Ab2 was used as the signal probe. Under the optimal conditions, the present immunoassay exhibited a wide quantitative range from 0.02 to 200 μg L(-1) with a detection limit of 0.006 μg L(-1), which was much lower than the WHO provisional guideline limit of 1.0 μg L(-1) for MC-LR in drinking water. The relative standard deviation was 4.8% and the recoveries for the spiked samples ranged from 84% to 115%, which indicated acceptable precision and accuracy for MC-LR. The present method is easier to perform and less time-consuming (the entire analysis process lasted about 40 minutes) and has been applied to the detection of MC-LR in different water samples successfully.


Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system.
This study was designed to investigate the cisplatin-induced alteration in renal antioxidant system and the nephroprotection with ebselen. Male Wistar rats were injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin plus ebselen. Rats were sacrificed three days post-treatment and plasma as well as kidney were isolated and analyzed. Plasma creatinine increased 598% following cisplatin administration alone which decreased by 158% with ebselen pretreatment. Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52% of control), while cisplatin plus ebselen injected rats had GSH values close to the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control, respectively, and malondialdehyde (MDA) levels increased 174% of control following cisplatin administration, which were restored to control levels after ebselen treatment. The renal platinum level did not significantly change with ebselen pretreatment. This study suggests that the protection offered by ebselen against cisplatin-induced nephrotoxicity is partly related to the sparing of antioxidant system.


MEDIAL FOOT LOADING ON ANKLE AND KNEE BIOMECHANICS.
BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries among females continues at disproportionate rates compared to males, with research indicating inconclusive multifactorial causality. Data from previous retrospective studies suggest an effect of abnormal foot and ankle biomechanics on pathology at the knee, including the ACL. OBJECTIVE: To determine if a relationship exists between plantar foot loading patterns during normal gait and high risk biomechanics purported to increase risk of ACL injury. METHODS: Dynamic barefoot plantar pressure distribution was measured on 33 female collegiate soccer players. Groups were divided according to their predominant gait loading pattern (medial or lateral). Three dimensional (3-D) motion analysis was conducted during drop vertical jumps to assess vertical ground reaction force and discrete angle and joint moment variables of the lower extremities. RESULTS: No significant differences occured in sagittal or coronal plane knee joint kinematics and kinetics between the medial and lateral loading groups. DISCUSSION: Dynamic foot and ankle biomechanics during gait do not appear to be related to lower extremity kinematics or kinetics during landing in collegiate female soccer players. CONCLUSION: The exact cause of the abnormal differences in female landing biomechanics has not been irrefutably defined. This study suggests no effect of foot and ankle biomechanics exists on the landing mechanics of female soccer players.


Huntingtin immunoreactivity in the rat neostriatum: differential accumulation in projection and interneurons.
Huntington's disease is caused by a mutation of the gene encoding the protein huntingtin. Features of the human disease, characterized by selective loss of neurons from the neostriatum, can be replicated in rodents by administration of excitotoxins. In both affected individuals and the rodent model, there is massive loss of striatal projection neurons with selective sparing of interneurons. Furthermore, in the human disease the earliest evidence of striatal injury is found in striosomal regions of the striatum. The mRNA encoding huntingtin is known to be expressed by neurons throughout the brain, a distribution which does not account for the selective patterns of neuronal death which are observed. Using fluorescence immunocytochemistry and confocal microscopy with an antibody to huntingtin, we have observed that in rats a subset of striatal projection neurons contains dense accumulations of huntingtin immunoreactivity (HT-ir), while most neurons in the striatum contain much smaller amounts. The intensely stained neurons are concentrated within the striatal striosomes, as defined by calbindin-D28K staining. In the matrix regions, relatively few neurons contain dense accumulations of HT-ir, and these cells always lack perikaryal staining for calbindin-D28K. Striatal interneurons, identified by the presence of immunoreactivity for choline acetyltransferase, parvalbumin, calretinin, or neuronal nitric oxide synthase, exhibit little or no HT-ir. The paucity of HT-ir in striatal interneurons, as well as the prominence of staining in a subset of striosomal neurons, mirrors the selective vulnerability of these different types of cells in early stages of human Huntington's disease and in rodent excitotoxic models of the disorder. Our observations suggest that mechanisms which modulate the accumulation of huntingtin may play a central role in the neuronal degeneration of Huntington's disease.


Loss of TIMP3, but not TIMP4, exacerbates thoracic and abdominal aortic aneurysm.
Aorta exhibits regional heterogeneity (structural and functional), while different etiologies for thoracic and abdominal aortic aneurysm (TAA, AAA) are recognized. Tissue inhibitor of metalloproteinases (TIMPs) regulate vascular remodeling through different mechanisms. Region-dependent functions have been reported for TIMP3 and TIMP4 in vascular pathologies. We investigated the region-specific function of these TIMPs in development of TAA versus AAA. TAA or AAA was induced in male and female mice lacking TIMP3 (Timp3-/-), TIMP4 (Timp4-/-) or in wildtype (WT) mice by peri-adventitial elastase application. Loss of TIMP3 exacerbated TAA and AAA severity in males and females, with a greater increase in proteinase activity, smooth muscle cell phenotypic switching post-AAA and -TAA, while increased inflammation was detected in the media post-AAA, but in the adventitia post-TAA. Timp3-/- mice showed impaired intimal barrier integrity post-AAA, but a greater adventitial vasa-vasorum branching post-TAA, which could explain the site of inflammation in AAA versus TAA. Severity of TAA and AAA in Timp4-/- mice was similar to WT mice. In vitro, Timp3 knockdown more severely compromised the permeability of human aortic EC monolayer compared to Timp4 knockdown or the control group. In aneurysmal aorta specimens from patients, TIMP3 expression decreased in the media in AAA, and in adventitial in TAA specimens, consistent with the impact of its loss in AAA versus TAA in mice. TIMP3 loss exacerbates inflammation, adverse remodeling and aortic dilation, but triggers different patterns of remodeling in AAA versus TAA, and through different mechanisms.


Exposure to stressful events during a peacekeeping mission may have a price: The impact on trait of negative and positive affect and mental health.
We evaluated the participants' negative affect, positive affect, post-traumatic stress disorder, and depression symptoms before and after a peacekeeping mission. Depression symptoms and positive affect after mission were significantly associated with exposure to stressful events during the mission, controlled by the respective characteristics before mission. Negative affect and post-traumatic stress disorder symptoms after mission had a tendency to be associated with exposure to stressful events during the mission, controlled by the respective characteristics before mission. In conclusion, even in healthy and physically active male peacekeepers, those more exposed to stressful events could be more vulnerable to present negative outcomes.


[Evaluation of primary tinnitus with fine puretone test and estimate of the technique].
Objective:To evaluate the relative factors of the severity and characteristics of primary tinnitus patients with fine puretone test(FPT) by three kinds of octaves, and to estimate the clinical application of this technique.Method:All subjects(n=90, ears=108), diagnosed with primary tinnitus, were recruited during July 2017 to February 2018 from the out-patients of Nanfang Hospital. In the prospective design, the patients were randomly divided into group 1/3 octave(n=30, ears=35), group 1/12 octave(n=30, ears=37) and group 1/24 octave(n=30, ears=36). Then tinnitus handicap inventory(THI), FPT, time and degree of residual inhibition(RI), time and degree of hyposensitization test, time attenuation test of masking(TATM) were used for evaluating the diseased and healthy ear performed separately.Result:Eighty-six patients were taken THI. The severity of tinnitus was no significant correlation with the gender,ear,sleep time and working time(P>0.05),but positive correlation with age(r=0.274, P=0.011) and duration of tinnitus(r=0.239, P=0.026). The selfassessment loudness score(SALS)(r=0.542,P=0.000) and the visual analogue score(VAS)(r=0.529, P=0.000) showed a moderate positive correlation. In the 1/24 octave, except for the TATM of the diseased ear group, the results of other groups were statistically different from the 1/3 octave(P<0.05), and much suitable than the 1/3 octave. Moreover, the results showed that the time of RI in the left and diseased ear group, the time of HT in the right, left and diseased ear group, the degree of HT in the right ear group were statistically different from the 1/12 octave(P<0.05) respectively, and much suitable than the 1/12 octave. The 1/12 octave was only statistically different from the 1/3 octave in TATM of the diseased ear group(P<0.05), and much suitable than the 1/3 octave.Conclusion:This study shows that gender, ear, sleep time, and working time had no significant effect on the severity of tinnitus, the age and duration of tinnitus have certain effects on the severity of tinnitus, the SALS, VAS score and the severity of tinnitus are moderately positively correlated. The 1/24 octave is significantly much suitable than the 1/3 octave and the 1/12 octave. And the technique of FPT is beneficial to improve the reliability and accuracy of the tinnitus evaluation.


Series: Pragmatic trials and real world evidence: Paper 5. Usual care and real life comparators.
Pragmatic trials may deliver real-world evidence on the added value of new medications compared with usual care and inform decision making earlier in development. This fifth paper in a series on pragmatic trials in the Journal discusses usual care as a comparator and the allocation of treatment strategies. The allocation and implementation of treatment strategies should resemble clinical practice as closely as possible. Randomization at the level of the site, as opposed to at the individual level, may be preferred. Data analysis according to the intention-to-treat principle is recommended, and crossover between treatment arms and strong treatment preferences may be accounted for in the study design in specific situations. Although usual care is the comparator of choice, this may differ substantially between centers and countries complicating comparator choice. Using clinical guidelines to define usual care can be helpful in standardizing comparator treatments; however, this may decrease the applicability of the results to real-life settings. Conversely, using multiple usual-care treatment arms will increase the complexity of the study. The specific objectives of the trial and design choices should be discussed with all stakeholders to realize the full potential of the pragmatic trial.


F-18 FDG PET identification of right atrium metastasis from a vesical carcinoma.
Fluorodeoxyglucose (FDG) positron emission tomography (PET) has been shown to be useful in the diagnosis and staging of various malignancies. The main advantage of PET is its high sensitivity in identifying malignancies at an early stage. The authors present a patient in whom transthoracic echography and MRI revealed a right atrial mass. The diagnosis was difficult between tumor and thrombus, but PET imaging correctly suggested a malignant tumor.


Drug interactions in African herbal remedies.
Herbal usage remains popular as an alternative or complementary form of treatment, especially in Africa. However, the misconception that herbal remedies are safe due to their "natural" origins jeopardizes human safety, as many different interactions can occur with concomitant use with other pharmaceuticals on top of potential inherent toxicity. Cytochrome P450 enzymes are highly polymorphic, and pose a problem for pharmaceutical drug tailoring to meet an individual's specific metabolic activity. The influence of herbal remedies further complicates this. The plants included in this review have been mainly researched for determining their effect on cytochrome P450 enzymes and P-glycoprotein drug transporters. Usage of herbal remedies, such as Hypoxis hemerocallidea, Sutherlandia frutescens and Harpagophytum procumbensis popular in Africa. The literature suggests that there is a potential for drug-herb interactions, which could occur through alterations in metabolism and transportation of drugs. Research has primarily been conducted in vitro, whereas in vivo data are lacking. Research concerning the effect of African herbals on drug metabolism should also be approached, as specific plants are especially popular in conjunction with certain treatments. Although these interactions can be beneficial, the harm they pose is just as great.


Infective Endocarditis Presenting as Complete Heart Block With an Unexpected Finding of a Cardiac Abscess and Purulent Pericarditis.
Intracardiac abscess resulting in complete heart block is an infrequent complication of infective endocarditis. Most presentations of endocarditis are limited to valvular and perivalvular structures, with varying degrees of heart block occurring in the minority of cases. We report a case of endocarditis manifesting as chest pain associated with ST segment elevation and complete heart block. The patient expired unexpectedly within a few hours of presentation. Postmortem examination revealed an atrial septal abscess, purulent pericardial collection, and fibrinous pericarditis. Spread of the abscess into the atrial septum was postulated to be the cause of the complete heart block. In endocarditis, the ominous development of heart block and a poor response to antibiotic therapy imply significant extension of the infection. Management therefore requires prompt ventricular pacing with consideration for valve replacement and possible pericardial drainage.


The relationship between social dysfunctioning and psychopathology among primary care attenders.
The extent of social dysfunctioning and its relationship to psychological disorders among Dutch primary care patients was examined. Social dysfunctioning in these patients was rather limited, but was more pronounced in patients with a psychological disorder than in those without. Disabilities were largely restricted to the occupational and social roles, with family role functioning and self-care relatively intact. Social dysfunctioning was moderately related to psychopathology, with higher levels of dysfunctioning in more severe and depressed cases. The extent of social dysfunctioning among patients with both anxiety and depression was similar to that of patients with a single diagnosis of depression. Depressed patients had a similar level of dysfunctioning to non-psychotic psychiatric out-patients. Analyses regarding the effects of diagnosis and severity on social dysfunctioning revealed considerable overlap between these two aspects of psychopathology. This study supports the need for a simultaneous but separate assessment of psychopathology and social dysfunctioning. However, future research should incorporate additional predictors of social dysfunctioning (e.g. personality, life events, long-term difficulties, physical disorders), and prospective studies should be conducted to clarify the temporal sequences of symptom severity, diagnosis, and comorbidity on the one hand, and social dysfunctioning on the other.


First direct lithiation of 2-pyridylpiperazine on solid phase.
[reaction: see text] The first direct lithiation of a pyridine derivative on solid phase has been realized. Metalation of polymer-bound 2-pyridylpiperazine with the BuLi-LiDMAE reagent followed by electrophilic quenching and subsequent cleavage provided a range of new useful C-6 substituted 2-piperazinylpyridines.


Rapid methods for detection and enumeration of Campylobacter spp. in foods.
Campylobacter spp. are the most commonly reported bacterial cause of acute diarrheal disease in humans throughout the world. Traditional cultural methods for the detection and quantitation of Campylobacterspp. are slow and tedious; therefore, specific, sensitive, and rapid methods for campylobacters are needed to collect sufficient data for risk assessment and food safety policy development. We developed several rapid methods based on polymerase chain reaction (PCR), DNA hybridization, hydrophobic grid membrane filters (HGMFs), and enzyme immunoassays (EIAs). A PCR assay targeting C. jejuni, combined with a simple sample preparation procedure, detects as few as 0.3 most probable number (MPN)/mL C. jejuni in naturally contaminated chicken rinses after 20-24 h enrichment. An HGMF-EIA method using a commercial polyclonal antibody for Campylobacter detects and enumerates thermophilic Campylobacter spp. from spiked chicken rinse and milk, and naturally contaminated chicken rinses. A C. jejuni-specific probe in an HGMF-DNA hybridization protocol specifically detects and quantitates C. jejuni in food samples. A dot-blot EIA combined with an MPN procedure quantitates thermophilic campylobacters from samples that might be difficult to filter through HGMFs.


Effects of cyanide on selenium metabolism in rats.
Adult male rats were given drinking water containing either 0 or 150 ppm cyanide for 2 weeks. They were then injected with 5 microCi 75Se-selenite, and excretion of radioactivity in urine and feces was determined. No difference in excretion of 75Se occurred during the rapid phase, but the cyanide-treated rats (T1/2 28 days) excreted significantly more 75Se in urine than control (T1/2 38 days) rats. Cyanide had no effect on excretion of 75Se in feces or on the distribution of 75Se in cytosolic proteins in liver, kidney, muscle or testes. In a second experiment weanling male rats were given water with either 0 or 150 ppm cyanide and were killed for glutathione peroxidase assay and selenium analysis in blood, kidney, liver, muscle and testes after 3, 6 or 9 weeks of treatment. Glutathione peroxidase activity and selenium concentrations were significantly reduced by cyanide in all tissues except testes.


Exposure to heavy metals and red blood cell parameters in children: A systematic review of observational studies.
Mechanistic studies show that heavy metals interfere with the hematopoietic system by inhibiting key enzymes, which could lead to anemia. However, the link between children's exposure and red blood cell (RBC) parameters has been inconsistent. We aimed to summarize evidence on human studies exploring the association between exposure to lead, mercury, cadmium, arsenic, and chromium VI and RBC parameters in children. Following the PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases for studies published between January 2010 and April 2022. Eligible papers included human observational studies that directly assessed exposure (internal dose) to the heavy metals under study and RBC parameters in participants aged ≤ 18 years. We excluded studies using hospital-based samples. Study quality was assessed using the National Institutes of Health's Quality Assessment Tools for Cohort and Cross-Sectional Studies. We synthesized the evidence using vote counting based on the direction of the relationship. Out of 6,652 retrieved papers, we included a total of 38 (33 assessing lead, four mercury, two cadmium, and two arsenic; chromium VI was not assessed in any included paper). More than half of the studies were conducted in Asia. We found evidence of a positive relationship between lead concentration and hemoglobin (proportion of studies reporting negative relationships = 0.750; 95% Confidence Interval (CI) 0.583, 0.874) and mean corpuscular hemoglobin (0.875; 95% CI 0.546, 0.986), and a positive relationship with red cell distribution width (0.000; 95%CI 0.000, 0.379). When considering only good-quality studies (24% of the Pb studies), only the relationship with hemoglobin levels remained (0.875; 95% CI: 0.546, 0.986). We found evidence of a negative relationship between lead concentration and hemoglobin and mean corpuscular hemoglobin and of a positive relationship with red cell distribution width in children. We also identified a need to conduct more studies in European countries. Future studies should use standardized practices and make efforts to increase study quality, namely by conducting comprehensive longitudinal studies. Our findings support the need to take further actions to limit heavy metal exposure during childhood.


A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.
Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development.


In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.
Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.


Does entrepreneurship education in China develop entrepreneurial intention? the role of self-efficacy and experience.
Entrepreneurship education has attracted much attention in recent years. However, the relationship between entrepreneurship education and entrepreneurial intention has not achieved an agreement yet. To reconcile these conflicting conclusions, we explore the effect of entrepreneurship education on entrepreneurial intention from the content of the entrepreneurship education programs and different types of individuals who have participated in the program. Leveraging the self-efficacy theory and event system theory, we examine the mediation of entrepreneurial self-efficacy from five dimensions and the moderation of entrepreneurial experience. The sample of this study comprised 243 individuals who participated in entrepreneurship education in China (female = 40.3%, The majority of responders with an age range from 21 to 30 years). The results reveal that entrepreneurship education has a significantly positive influence on entrepreneurial intention (β = 0.331, p < 0.001). Entrepreneurial self-efficacies in searching (β = 0.382, p<0.001), planning (β = 0.249, p<0.001), and marshaling (β = 0.134, p<0.05) play mediating roles in the relationship between entrepreneurship education and entrepreneurial intention. We also find that entrepreneurial experience negatively moderates the relationship between entrepreneurship education and entrepreneurial intention (β = -0.212, p<0.05). The results have implications for entrepreneurship education scholars and policymakers in China.


Recombination of Protons Accelerated by a High Intensity High Contrast Laser.
Short pulse, high contrast, intense laser pulses incident onto a solid target are not known to generate fast neutral atoms. Experiments carried out to study the recombination of accelerated protons show a 200 times higher neutralization than expected. Fast neutral atoms can contribute to 80% of the fast particles at 10 keV, falling rapidly for higher energy. Conventional charge transfer and electron-ion recombination in a high density plasma plume near the target is unable to explain the neutralization. We present a model based on the copropagation of electrons and ions wherein recombination far away from the target surface accounts for the experimental measurements. A novel experimental verification of the model is also presented. This study provides insights into the closely linked dynamics of ions and electrons by which neutral atom formation is enhanced.


Nonuniform piezoelectric circular plate flexural transducers with underwater applications.
An analytical treatment is presented for circular flexural plate transducers that have nonuniform electromechanically active-passive mechanical systems with particular interest in underwater applications. The analysis is made using the energy method that was previously applied to calculating parameters of uniform fully active (bimorph) circular plate transducers [B. S. Aronov, J. Acoust. Soc. Am. 118(2), 627-637 (2005)]. It is shown that the vibration mode shapes remain sufficiently similar to those for uniform plates for a large range of relative dimensions of active and passive laminates of radially nonuniform mechanical systems, and they may be used for calculating transducer parameters. Therefore the transducers can be considered as having a single degree of freedom, and their operational characteristics can be determined using the same technique as previously used for uniform plates. Dependences of the resonance frequencies, effective coupling coefficients, and parameters of the equivalent electromechanical circuit on relative dimensions of active and passive laminates for several combinations of the active and passive materials are presented and compared with those parameters of uniform plates having the same overall dimensions. The results of experimental verification are in good agreement with theoretical predictions.


PDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarization.
We recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate morphogens. Of note, a novel morphogenic factor, PDZ-domain containing-2 (PDZD2) and its secreted form (sPDZD2) were ubiquitously expressed in the PPCs. Our goals for this study were to evaluate the potential role of sPDZD2 in stimulating PPC differentiation and to establish the optimal concentration for such stimulation. We found that 10(-9)M sPDZD2 promoted PPC differentiation, as evidenced by the upregulation of the pancreatic endocrine markers (PDX-1, NGN3, NEURO-D, ISL-1, NKX 2.2, NKX 6.1) and INSULIN mRNA. Inhibited endogenous production of sPDZD2 suppressed expression of these factors. Secreted PDZD2 treatment significantly elevated the C-peptide content of the ICCs and increased the basal rate of insulin secretion. However, they remained unresponsive to glucose stimulation, reflected by a minimal increase in GLUT-2 and GLUCOKINASE mRNA expression. Interestingly, sPDZD2 treatment induced increased expression of the L-type voltage-gated calcium channel (Ca(v)1.2) in the ICCs, triggering calcium ion influx under KCl stimulation and conferring an ability to secrete insulin in response to KCl. Pancreatic progenitor cells from 10- and 13-week fetal pancreata showed peak expression of endogenous sPDZD2, implying that sPDZD2 has a specific role in islet development during the first trimester. In conclusion, our data suggest that sPDZD2 promotes functional maturation of human fetal PPC-derived ICCs, thus enhancing its transplanting potentials.


Screening and Validation of Housekeeping Genes of the Root and Cotyledon of Cunninghamia lanceolata under Abiotic Stresses by Using Quantitative Real-Time PCR.
Cunninghamia lanceolata (Chinese fir) is a fast-growing and commercially important conifer of the Cupressaceae family. Due to the unavailability of complete genome sequences and relatively poor genetic background information of the Chinese fir, it is necessary to identify and analyze the expression levels of suitable housekeeping genes (HKGs) as internal reference for precise analysis. Based on the results of database analysis and transcriptome sequencing, we have chosen five candidate HKGs (Actin, GAPDH, EF1a, 18S rRNA, and UBQ) with conservative sequences in the Chinese fir and related species for quantitative analysis. The expression levels of these HKGs in roots and cotyledons under five different abiotic stresses in different time intervals were measured by qRT-PCR. The data were statistically analyzed using the following algorithms: NormFinder, BestKeeper, and geNorm. Finally, RankAggreg was applied to merge the sequences generated from three programs and rank these according to consensus sequences. The expression levels of these HKGs showed variable stabilities under different abiotic stresses. Among these, Actin was the most stable internal control in root, and GAPDH was the most stable housekeeping gene in cotyledon. We have also described an experimental procedure for selecting HKGs based on the de novo sequencing database of other non-model plants.


Nonvolatile multi-level adjustable optical switch based on the phase change material.
For the advantages of the faster computation speed and lower energy consumption, all-optical computation has attracted great attention compared with the traditional electric computation method. Optical switches are the critical elementary units of optical computation devices. However, the traditional optical switches have two shortcomings, expending the outside energy to keep the switch state and the weak multi-level adjustable ability, which greatly restrict the realization of the large-scale photonic integrated circuits and optical spiking neural networks. In this paper, we use a subwavelength grating slot-ridge (SWGSR) waveguides on the silicon platform to design a nonvolatile multi-level adjustable optical switch based on the phase change material Ge2Sb2Te5 (GST). Changing the phase state of GST can modulate the transmission of the optical switch, and the change of the optical transmittance of the optical switch is about 70%, which is much higher than that of previous optical switches. As no static power is required to maintain the phase state, it can find promising applications in optical switch matrices and reconfigurable optical spiking neural networks.


The relationship between self-reported health and mental health problems among older adults in New Zealand: experiential avoidance as a moderator.
This study sought to examine the influence of experiential avoidance (EA) as a moderating variable between reported physical health problems and anxiety and depression among older adults. Experiential avoidance has been found in previous studies to be strongly associated with a number of psychological disorders in younger adults but has received minimal attention in older populations. Two-hundred-and-eight individuals from New Zealand between the ages of 70 and 92 years old participated in this study. The Geriatric Anxiety Inventory, the Geriatric Depression Scale and the Acceptance and Action Questionnaire were used to measure anxiety, depression and EA, respectively. It was hypothesized that self-reported health (SRH) and EA would be associated with depression and anxiety at the zero order level. We also hypothesized that EA would be a unique predictor of depression and anxiety and would moderate the relationships between SRH and both depression and anxiety. Multiple regression analyses indicated that EA explained 8% of the unique variance in depression, 20% in anxiety and moderated the relationships between SRH and both depression and anxiety. This study also found that the relationships involving EA were more pronounced with anxiety as compared with depression in this elderly sample. The theoretical and practical applications of these findings are discussed.


Idiopathic external root resorption associated to hypercalciuria.
Although external root resorption (ERR) is a physiological process in deciduous dentition, it is very infrequent in permanent dentition - where the phenomenon is related to the existence of inadequate occlusal forces, periodontal pathology and microtraumatisms, etc. However, in many cases root resorption cannot be attributed to any concrete cause; such cases are defined as idiopathic external root resorption (IERR). Epidemiological studies have found that the underlying cause can only be established in 5% of all ERR. The present study describes three cases of IERR with different degrees of involvement and associated to mild calciuria and a history of nephrolithiasis. Hypercalciuria with normal blood calcium levels is usually idiopathic and exhibits a familial trait, with a prevalence of 20-40 cases per 1,000 individuals in adults. A form of hypercalciuria associated to nephrolithiasis with a mutation of the CLCN5 gene has been identified, involving low molecular weight proteinuria - though this mutation has not been uniformly demonstrated in most cases of idiopathic hypercalciuria. The peculiarity of the cases described in the present study is attributable to the coexistence of IERR with normocalcemic hypercalciuria and nephrolithiasis - thus pointing to the need for in-depth evaluation of the possible association of these three clinical situations.


Sex differences in behavioral responses during a conditioned flight paradigm.
Females exhibit greater susceptibility to trauma- and stress-related disorders compared to males; therefore, it is imperative to study sex differences in the mode and magnitude of defensive responses in the face of threat. To test for sex differences in defensive behavior, we used a modified Pavlovian fear conditioning paradigm that elicits clear transitions between freezing and flight behaviors within individual subjects. Female mice subjected to this paradigm exhibited more freezing behavior compared to males, especially during the intertrial interval period. Female mice also exhibited more freezing in response to conditioned auditory stimuli in the last block of extinction training. Furthermore, there were sex differences in the expression of other adaptive behaviors during fear conditioning. Assaying rearing, grooming, and tail rattling behaviors during the conditioned flight paradigm yielded measurable differences across sessions and between males and females. Overall, these results provide insight into sex-dependent alterations in mouse behavior induced by fear conditioning.


Possible role of S-equol on bone loss via amelioration of inflammatory indices in ovariectomized mice.
S-equol is a natural metabolite of the soy isoflavone, daidzein, produced by intestinal bacteria. S-equol has been shown to have greater estrogenic activity than other soy isoflavones and prevent bone loss in post-menopausal women. Estrogen regulates both bone remodeling and hemopoiesis in the bone marrow, these processes that communicate closely with each other. In this study, we investigated the effect of S-equol on bone mass and gene expression of bone marrow cells in ovariectomized (OVX) mice. Female ddY strain mice, aged 12 weeks, were either sham operated or OVX. The OVX mice were randomly divided into two groups: (1) OVX control and (2) OVX fed a 0.06% (w/w) S-equol supplemented diet. After 2 weeks, the trabecular bone volume of the femoral distal metaphysis was markedly reduced in OVX mice. However, treatment with equol was observed to ameliorate this. Expression of inflammatory-, osteoclastogenesis- and adipogenesis-related genes was increased in OVX mice compared with sham mice, and equol was observed to suppress their expression. The present study demonstrates that equol might ameliorate bone loss caused by estrogen deficiency through regulating hemopoiesis and production of inflammatory cytokines in bone marrow cells.


Follicular carcinoma of thyroid following successful liver transplantation--a report.
Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients.


Potential for local resection with sentinel node basin dissection for early gastric cancer based on the distribution of primary sites.
Based on the sentinel node (SN) concept, function-preserving surgery with SN basin dissection (SNBD) can be performed for SN-negative early gastric cancers. Particularly, a resection area can be minimized when the SN basin and primary site are closely localized. The aim of this study was to compare probabilities of being candidates for local resection with SNBD based on tumor location among patients with early gastric cancer. We retrospectively analyzed 358 patients who underwent surgery with SN mapping for gastric cancer in our institution from November 1999 to April 2014. The proportion of patients who had a localized single basin and the distributions of the SN basins and primary sites were investigated. Patients with single basin drainage excluding remote sentinel node basin were considered as candidates for local resection with SNBD. Of the 358 patients, 191 (53%) patients were considered eligible for local resection with SNBD. Patients with tumors located in the upper third of the stomach were more likely candidates for local resection than those with tumors in other locations (upper third, 68%; middle third, 50%; and lower third, 51%), whereas patients with tumors located in the anterior wall were less likely candidates than those with tumors other locations (anterior wall, 31%; posterior wall, 58%; greater curvature, 55%; and lesser curvature, 57%). We found that > 50% of the patients indicated for SN navigation surgery, particularly those with tumors in the upper third of the stomach, potentially could undergo partial resection with SNBD.