The role of NF-κB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy.
Breast cancer (BC) is the second most fatal disease and is the prime cause of cancer allied female deaths. BC is caused by aberrant tumor suppressor genes and oncogenes regulated by transcription factors (TFs) like NF-κB. NF-κB is a pro-inflammatory TF that crucially alters the expressions of various genes associated with inflammation, cell progression, metastasis, and apoptosis and modulates a network of genes that underlie tumorigenesis. Herein, we focus on NF-κB signaling pathways, its regulators, and the rationale for targeting NF-κB. This review also includes TFs that maintain NF-κB crosstalk and their roles in promoting angiogenesis and metastasis. In addition, we discuss the importance of combination therapies, resistance to treatment, and potential novel therapeutic strategies including nanomedicine that targets NF-κB.


Hemodynamics and blood flow distribution following prolonged circulation at 5 degrees C.
Circulation was maintained in profoundly hypothermic dogs for 8 h at temperatures below 10 degrees C. During cooling to 5 degrees C cardiac output and blood pressure decreased and peripheral resistance rose. Thereafter, circulatory dynamics remained relatively stable over the next 6 h with a gradual decline in blood pressure. The proportion of blood flow to the heart and brain increased with cooling and remained elevated throughout the hypothermia period. Despite continued circulation, pulmonary edema developed after 5-7 h and the dogs were nonviable when rewarmed.


Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis.
Two types of tumor necrosis factor receptors have been characterized, both capable of transmitting the signal and exerting the biological functions of TNF and lymphotoxin. We measured the plasma concentrations of two types of TNF binding proteins (sTNFR-A and sTNFR-B) in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) using an enzyme-linked binding assay. In normal controls (n = 43), mean plasma concentrations were 1030 +/- 55 and 1461 +/- 59 pg/ml for sTNFR types A and B, respectively. In 67 patients with moderate RA, mean levels were 1422 +/- 82 pg/ml (type A) and 2088 +/- 109 pg/ml (type B); in 34 patients with severe RA, 2588 +/- 279 pg/ml and 4494 +/- 550 pg/ml, respectively, were measured (P less than 0.0001 compared to normal controls). Concentrations of both type A and type B sTNFR were highly correlated in severe RA (R2 = 0.7) but not in SpA or normal controls. T lymphocytes in synovial fluid of patients with RA expressed predominantly type A TNF receptors on their surface; in some patients a weaker expression of type B receptors was also detectable. Soluble TNF binding proteins in patients with RA were able to neutralize TNF in a cytotoxicity assay, demonstrating their ability to act as "TNF-inhibiting factors". We conclude that both types of TNF receptors are parameters of disease activity in RA and may also act as TNF antagonists.


VA cooperation strengthens vets' care, education.
A unique partnership between the University of Iowa College of Medicine and 3 Veterans Administration hospitals is described.


How apps are changing family medicine.
Medical applications for smartphones and tablets are so ubiquitous that it's easy to become a victim of app overload. Here's a look at FDA-approved apps, reference apps, and apps that FPs are "prescribing."


Identification and immunologic property of macrophage migration inhibitory factor (MIF) in grass carp (Ctenopharynogodon idella).
Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, plays an important regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. However, the immunologic property of MIF in freshwater fish is limitedly known by now. In the present study, MIF gene was identified in grass carp. Bioinformatics analysis revealed that the molecular weight of grass carp MIF protein was 12.377 kDa and it could also bind to CD74. MIF gene was predominantly expressed in immune tissues including spleen and head kidney, then liver, skin, gill, intestine and blood, while a relative low level expression in heart, brain, fat and red muscle. The predicted receptor and tissues distribution of MIF implied the immunologic activity of grass carp MIF. Then grass carp MIF antigen and the polyclonal antibodies against it were prepared. Using cadmium as an immunosuppressive agent, MIF expression in spleen and head kidney was depressed in a dose-dependent manner with cadmium consumption. On the same time, white blood cell count decrease displayed a similar pattern with MIF expression, which suggested a possible positive correlation between MIF and white blood cell count. Thereafter, MIF enhanced the viability of grass carp peripheral blood leukocytes and inhibited cell apoptosis with depressed reactive oxygen species production in vitro. In addition, recombinant grass carp MIF promoted tumor necrosis factor-alpha (TNF-α), interleukin 1β (IL1β) and interleukin 6 (IL6) secretion from peripheral blood leukocytes. These results indicated the immunologic property of grass carp MIF.


Metaplasia of the lung respiratory epithelium and antibody dynamics in mice repeatedly infected with various subtypes of influenza virus A.
Mice were repeatedly infected with consecutive doses of mouse-adapted strains of influenza virus A HON1, H1N1, H2N2, and H3N2. Homo- and heterologous antibody levels as well as the incidence of metaplasia were followed. Statistically significant correlation was found between the metaplasia incidence and higher level of antibodies homologous to virus used for a given challenge dose.


Cholecalciferol- and α-tocopherol-loaded walnut oil emulsions stabilized by whey protein isolate and soy lecithin for food applications.
To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions. All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model. This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.


Hydrogen peroxide production by liver mitochondria in different species.
The objective of this study was to further examine the relationship between oxygen free radicals and the aging process in animals. The rate of H2O2, a product of superoxide anion radical dismutation, released by liver mitochondria, was measured in the mouse, rat, guinea pig, rabbit, pig and cow as well as in flight muscle mitochondria of Drosophila melanogaster and the housefly, Musca domestica. The rate of H2O2 generation was inversely related to the maximum life span potential (MLSP) of the species. A 42-fold difference in the rate of H2O2 secretion was found among mammals and an up to 300-fold difference was noted between the insects and the mammals. Results of this study indicate that under identical conditions mitochondria from animals with low MLSP release relatively greater amounts of H2O2.


Assessment of the proposed pseudo-potential theoretical model for the static and dynamic Raman scattering intensities: Multivariate statistical approach to quantum-chemistry protocols.
Accurate calculation of molecular polarizabilities and Raman intensities required high-level correlated wave functions (CCSD) and large basis set with the inclusion of electronic correlation within experimental precision. These requirements, in terms of time and computation, are economically costly. Polarized Gaussian basis sets adapted to effective core potentials (ECPs) for the static and frequency dependent Raman intensities is presented. The results of the proposed basis sets at CCSD and DFT levels in comparison with Sadlej-pVTZ, as reference basis set, show quite a good quantitative agreement in the properties with a valuable reduction in the computational time and resources. Multivariate principal component analysis (PCA) was performed to study the assessment of the efficiency of proposed methodology and diagnose the inherent information related to the kind of normal vibrational mode of each molecule, based on the variations in the computed Raman intensities. The results, in the form of score-plots, explored a clear segregation and classification among the Raman intensities data, revealing its dependence on the excitation frequencies of laser and nature of the vibrational mode of each molecule of interest. Moreover, the projection of the loadings-plots of the PCs successfully enabled to classify the most correlated computational methods in to the same groups, and made isolations of the less efficient basis functions at the corresponding theoretical method.


Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair.
Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy. The crimped nanofiber scaffold (CNS) features bionic tensile stress and induces chondrogenic differentiation, laying credible basis for in vivo experimentation. After repairing a rabbit massive rotator cuff tear using a CNS for 3 months, the continuous translational tendon-to-bone interface was fully regenerated, and fatty infiltration was simultaneously inhibited. Instead of micro-CT, μCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1 μm. This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.


Role of the tympanic ring in the pathogenesis of congenital cholesteatoma.
Topographic study of congenital cholesteatomas revealed that the majority of these congenital epidermal cysts occur near the tympanic isthmus of the middle ear. Since this is the junction of the first and second brachial arch, the origin of the cholesteatoma could be linked to the migration of the external canal ectoderm into the middle ear at the early stage of development. Embryologic study showed that the tympanic ring plays an important role in limiting the medial extent of the external canal to the level of the tympanic annulus. Migration of the ectodermal tissue into the middle ear beyond the annulus is likely to be caused by the failure of this inhibitory function of the tympanic ring. Microscopic sections of human fetuses were studied to determine the developmental relationships between the external canal ectoderm and the tympanic ring. A section from a 161/2-week fetus showed significant papillary ectodermal tissue projection into the mesenchyme near the tympanic isthmus, while the tympanic ring was absent in that site. Anatomical distance between the tympanic ring and the internal auditory canal is extremely short in these fetuses. This is suggestive of the source of petrous cholesteatomas from the canal ectodermal migration. These observations form the basis of the author's theory that the pathogenesis of congenital cholesteatomas is caused by migration of external canal tissue into the tympanic isthmus or into the petrous bone as a result of developmental error in which the advancing external canal ectoderm failed to receive stop signal of the tympanic ring that contains the ectoderm at the annular plane.


Effects of Lactobionic Acid on Pig Growth Performance and Chemical Composition of Pork.
Lactobionic acid is an innovative product obtained in the fermentation process of cheese or curd whey, and it has several beneficial properties. Therefore, it may have potential application in animal feeding. Currently, lactobionic acid is not widely used yet in feeding farm animals. Therefore, the aim of our study was to evaluate the effect of lactobionic acid (LBA) on pig growth performance and pork quality. Two groups of pigs (control and trial, 26 piglets each) were completed. The control group received compound feed, whereas the trial group's feed was supplemented with LBA (0.17 kg per 100 kg of feed). Carcass weight and meat pH were determined. The subcutaneous fat layer S (mm) was measured. Lean meat content was determined using the SEUROP classification. Amino acids and fatty acids in pork were evaluated. The addition of LBA to pig feed significantly increased the live weight gain and slaughter yield of pigs, but the samples had a slightly thicker backfat layer. Results obtained showed higher concentration of amino acids in the trial group but slightly lower pork fat quality in the same group. Lactobionic acid has the potential for applications in pig feeding.


Non-enzymatic electrochemical dopamine sensing probe based on hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure.
A non-enzymatic dopamine electrochemical sensing probe was developed. A hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure was prepared by a facile hydrothermal approach. The combination of Zn, which has an abundance of electrons, and Co3O4 exhibited a synergistically electron-rich nanocomposite. The crystallinity of the nanostructure was investigated using X-ray diffraction. A scanning electron microscope (SEM) was used to examine the surface morphology, revealing hexagonal nanoparticles with an average particle size of 400 nm. High-resolution transmission electron microscopy (HR-TEM) was used to confirm the nanostructure of the doped material. The nanostructure's bonding and functional groups were verified using Fourier transform infrared spectroscopy (FTIR). The electrochemical characterization was conducted by using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and amperometry. The resistivity of the electrode was confirmed through EIS and showed that the bare glassy carbon electrode (GCE) exhibited higher charge transfer resistance as compared to modified Zn-Co2O4/GCE. The sensing probe was developed by modifying the surface of GCE with Zn-Co2O4 nanostructure and tested as an electrochemical sensor for dopamine oxidation; it operated best at a working potential of 0.17 V (vs Ag/AgCl). The developed sensor exhibited a low limit of detection (0.002 µM), a high sensitivity (126 µA. µM-1 cm-2), and a wide linear range (0.2 to 185 µM). The sensor showed a short response time of < 1 s. The sensor's selectivity was investigated in the presence of coexisting species (uric acid, ascorbic acid, adrenaline, epinephrine, norepinephrine, histamine, serotonin, tyramine, phenethylamine, and glucose) with no effects on dopamine determination results. The developed sensor was also successfully used for determining dopamine concentrations in a real sample.


Self-organized alternating chimera states in oscillatory media.
Oscillatory media can exhibit the coexistence of synchronized and desynchronized regions, so-called chimera states, for uniform parameters and symmetrical coupling. In a phase-balanced chimera state, where the totals of synchronized and desynchronized regions, respectively, are of the same size, the symmetry of the system predicts that interchanging both phases still gives a solution to the underlying equations. We observe this kind of interchange as a self-emerging phenomenon in an oscillatory medium with nonlinear global coupling. An interplay between local and global couplings renders the formation of these alternating chimeras possible.


Physical Performance During the Menopausal Transition and the Role of Physical Activity.
To examine longitudinal changes in physical performance during the menopausal transition and the role of physical activity (PA) in these changes. Based on follicle-stimulating hormone levels and bleeding diaries, women (47-55 years) were classified as early (n = 89) and late perimenopausal (n = 143) and followed prospectively until postmenopausal status, with mean duration of 17.5 and 13.8 months, respectively. Physical performance was measured by handgrip force, knee extension torque, vertical jumping height, maximal walking speed, and 6-minute walking distance. Physical activity was self-reported and categorized as inactive, low, medium, and high. Longitudinal associations of menopausal status, physical performance, and related changes with PA level were analyzed using generalized estimation equations adjusted for duration of hormonal therapy. A significant decline over the menopausal transition in handgrip force (-2.1%, 95% CI -3.8 to -0.4), knee extension torque (-2.6%, 95% CI -4.5 to -0.8), and vertical jumping height (-2.6%, 95% CI -4.2 to -1.1) and a significant increase in 6-minute walking distance (2.1%, 95% CI 1.4 to 2.7) were observed in the total sample. A significant interaction of PA by time was observed in handgrip force and in vertical jumping height. High PA women had greater increase in handgrip strength but greater decline in vertical jumping height than medium, low, and inactive women (all p ≤ .001). Both early and late perimenopausal women show decline in muscle strength and power during the transition to postmenopause. Physical activity seems to influence physical performance during the menopausal transition but understanding the benefits of PA requires interventional studies.


[Capillary bed of the mammillary bodies of the posterior hypothalamus in hypertension in young and old persons].
Young patients with essential hypertension as compared to control were shown to have an increased diameter of the ultracirculation, elevated levels of nucleic acids in the endotheliocyte nuclei with the predominance of low optical density nuclei. Elderly subjects of the respective groups showed no difference between the parameters studied.


Esophageal cancers with synchronous or antecedent head and neck cancers: a more formidable challenge?
The presence of synchronous or antecedent head and neck cancers may complicate management of patients with primary esophageal cancer. From January 1982 to December 2004, by means of a prospectively collected database, we compared information from 119 patients with esophageal cancers who had synchronous or antecedent head and neck cancers with information from 1555 patients who only had squamous cell esophageal cancer in a tertiary referral academic hospital. There were far more men and younger patients in those who had head and neck cancers, and multicentric tumors were also more common. Hypopharyngeal tumors were the most frequently encountered head and neck cancer and were found in 36.1% of patients. Resection rates of the primary esophageal cancers were similar in those who had head and neck cancers and in those who only had esophageal cancer (60.7% vs. 61.7% P = .74). Overall postoperative complication rates were not different. Thirty-day mortality rates were 0% and 2.9% for those who did and did not have head and neck tumors, respectively (P = .25). The respective hospital mortality rates were 10.3% and 9.5% (P = .83). Median survival for resectable esophageal cancers was 9.2 months for the former group and 13.4 months for the latter (P = .02). Esophagectomy rates did not differ when synchronous or antecedent head and neck cancers were present. Similar postoperative morbidity and mortality rates could be achieved. The presence of additional head and neck tumors imparted a worse long-term prognosis.


Strategic design of precautionary measures for airport passengers in times of global health crisis Covid 19: Parametric modelling and processing algorithms.
Presently, the negative results of a pandemic loom in a threatening manner on an international scale. Facilities such as airports have contributed significantly to the global spread of the COVID-19 virus. Therefore, in order to address this challenge, studies on sanitary risk management and the proper application of countermeasures should be carried out. To measure the consequences over passenger flow, simulation modelling has been set up at Casablanca Mohammed V International Airport. Several scenarios using daily traffic data were run in different circumstances. This allowed the development of some assumptions regarding the overall capacity of the airport. The proposed simulations make it possible to calculate the number of passengers to be processed in accordance with the available check-in counters based on the proposed sanitary measures.


Comprehensive cardiac evaluation to maximal exercise in a contemporary population of prepubertal children.
Heart rate (HR) is a biomarker used to measure physiological function, health status and cardiovascular autonomic function. The purpose of this study was to determine sex- and age-specific reference values for cardiac autonomic function at rest, during maximal exercise and the recovery phase in prepubertal children. Five hundred and twelve healthy children 7-11 years of age performed a Léger test. A heart RR-interval monitor recorded the heart data and a specific software analysed the cardiac autonomic response through HR and HR variability (HRV). It analysed HR before the test (resting HR, RHR), during the test (HRpeak) and HR recovery (HRR) in the first minute (HRR1) and the fifth minute (HRR5). The values are mean ± SD. Collectively, 91.2% of girls and 92.3% of boys were within the recommended ranges regarding RHR. The average HRpeak was 199 ± 10.83 b.p.m. and 96.8% of girls and 95.3% of boys were within the minimum threshold value recommended (180 b.p.m.). Boys showed lower values of RHR than girls (p < 0.001) and larger values of HRR 1 and HRR5 (p < 0.001). This study comprehensively provides a reference set of data for the most important HR variables that can be obtained during exercise testing in prepubertal children regarding age and sex and in a field setting. This is the first study to provide reference values of autonomic cardiac function at rest, during maximal exercise and during the recovery period in prepubertal children aged 7-11 years. Despite the early age of participants, cardiorespiratory fitness, RHR and HRR are different according to sex. Aerobic performance and HRpeak have a negative correlation with body mass index and cardiometabolic risk.


MLH1 mediates cytoprotective nucleophagy to resist 5-Fluorouracil-induced cell death in colorectal carcinoma.
Colorectal Cancer (CRC) with Microsatellite instability (MSI) and mutLhomolog-1 (MLH1) gene deficiency are less aggressive than MLH1 proficient cancers. MLH1 is involved in several cellular processes, but its connection with the autophagy-dependent cellular response towards anticancer drugs remains unclear. In this study, we aimed to investigate the interaction between MLH1 and the autophagy marker LC3, which facilitated nucleophagy induction, and its potential role in determining sensitivity to 5-Fluorouracil (5-FU) induced cell death. To examine the role of MLH1 in DNA-damage-induced nucleophagy in CRC cells, we utilized a panel of MLH1 deficient and MLH1 proficient CRC cell lines. We included a parental HCT116 cell line (MLH1-/-) and its isogenic cell line HCT116 MLH1+/- in which a single allele of the MLH1 gene was introduced using CRISPR-Cas9 gene editing. We observed that MLH1 proficient cells were less sensitive to the 5-FU-induced cytotoxic effect. The 5-FU induced DNA damage led to LC3 up-regulation, which was dependent on MLH1 overexpression. Moreover, immunofluorescence and immunoprecipitation data showed LC3 and MLH1 were colocalized in CRC cells. Consequently, MLH1 dependent 5-FU-induced DNA damage contributed to the formation of micronuclei. These micronuclei colocalize with autolysosome, indicating a cytoprotective role of MLH1 dependent nucleophagy. Interestingly, siRNA knockdown of MLH1 in HCT116 MLH1+/- prevented LC3 upregulation and micronuclei formation. These novel data are the first to show an essential role of MLH1 in mediating the chemoresistance and survival of cancer cells by increasing the LC3 expression and inducing nucleophagy in 5-FU treated CRC cells.


Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.
Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25 μg/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48 h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1β, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-α levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus.


Introduction of electronic referral from community associated with more timely review by secondary services.
Electronic referral (eReferral) from community into public secondary healthcare services was introduced to 30 referring general medical practices and 28 hospital based services in late 2007. To measure the extent of uptake of eReferral and its association with changes in referral processing. Analysis of transactional data from the eReferral message service and the patient information management system of the affected hospital; interview of clinical, operational and management stakeholders. eReferral use rose steadily to 1000 transactions per month in 2008, thereafter showing moderate growth to 1200 per month in 2010. Rate of eReferral from the community in 2010 is estimated at 56% of total referrals to the hospital from general practice, and as 71% of referrals from those having done at least one referral electronically. Referral latency from letter date to hospital triage improves significantly from 2007 to 2009 (p<0.001), from a paper referral median of 8 days (inter-quartile range, IQR: 4-14) in 2007 to an eReferral median of 5 days (IQR: 2-9) and paper referral median of 6 days (IQR: 2-12) in 2009. Specialists upgrade the referrer-assigned eReferral priority in 19.2% of cases and downgrade it 18.6% of the time. Clinical users appreciate improvement of referral visibility (status and content access); however, both general practitioners and specialists point out system usability issues. With eReferrals, a referral's status can be checked, and its content read, by any authorized user at any time. The period of eReferral uptake was associated with significant speed-up in referral processing without changes in staffing levels. The eReferral system provides a foundation for further innovation in the community-secondary interface, such as electronic decision support and shared care planning systems. We observed substantial rapid voluntary uptake of eReferrals associated with faster, more reliable and more transparent referral processing.


Epithelial oral mucosal cells: Do they behave differently when exposed to oral carcinogens?
To assess the level of maturation and proliferation of epithelial cells and the correlation with immunocytochemical expression of adhesion (E-cadherin) and cell differentiation (involucrin) markers. Cytopathological samples were obtained from four groups of patients: control (CG, n=30); alcohol/tobacco (ATG, n=31), leucoplakia (LG, n=31), and squamous cell carcinoma (SCCG, n=22). Cytopathological smears were collected from all groups for AgNOR, Papanicolaou and immunocytochemical staining. There was an increase in anucleated cells in ATG compared to CG and in LG compared to lesion-free groups (P<.05). In addition, there was a higher rate of intermediate cells in lesion-free groups than in LG (P=.001). When these findings were correlated with positive E-cadherin expression, there was a smaller number of anucleated and intermediate cells (P<.05). The proliferation rate was higher in the SCCG than in the CG (P<.05) and in the ATG compared to LG (P<.05). Moreover, cell proliferation increased in the presence of positive E-cadherin expression in the ATG and LG. No statistically significant results were obtained for involucrin analysis. Cytopathology combined with quantitative techniques such as Papanicolaou, AgNOR, and immunocytochemical expression of E-cadherin detects changes associated with oral carcinogenesis. The innovative approach used in this study allows assessing the expression of cell adhesion (E-cadherin) and differentiation (involucrin) markers by means of oral mucosal cytopathology. The E-cadherin imunocytochemical expression indicated changes associated with the oral carcinogenesis process. An increase in cell proliferation rate in oral squamous cell carcinoma group was associated with the lower immunoexpression of E-cadherin. Cytopathology combined with quantitative techniques and immunocytochemical expression of E-cadherin may detect early alterations associated with oral carcinogenesis.


Comparative genetics of the poly-Q tract of ataxin-1 and its binding protein PQBP-1.
Human PQBP-1 is known to interact with triplet repeat disease gene products such as ataxin and huntingtin through their poly-glutamine (poly-Q) tracts. The poly-Q tracts show extensive variation in both the number and the configuration of repeats among species. A surface plasmon resonance assay showed clear interaction between human PQBP-1 and Q(11), representative of the poly-Q tract of the ataxin-1 of Old World monkeys. No response was observed using Q(2)PQ(2)P(4)Q(2), representative of the poly-Q tract of the ataxin-1 of New World monkeys. This implies that the interaction of human PQBP-1 with ataxin-1 is limited to humans and closely related species. Comparison of the human and mouse PQBP-1 sequences showed an elevated amino acid substitution rate in the polar amino acid-rich domain of PQBP-1 that is responsible for binding to poly-Q tracts. This could have been advantageous to the new biological function of human PQBP-1 through poly-Q tracts.


Comprehensive analysis of differentially expressed profiles of mRNA, lncRNA, and miRNA of Yili geese ovary at different egg-laying stages.
The development of the ovaries is an important factor that affects egg production performance in geese. Ovarian development is regulated by genes that are expressed dynamically and stage-specifically. The transcriptome profile analysis on ovarian tissues of goose at different egg laying stages could provide an important basis for screening and identifying key genes regulating ovarian development. In this study, 4 ovary tissues at each breeding period of pre-laying (PP), laying (LP), and ceased-laying period (CP), respectively, with significant morphology difference, were used for RNA extraction and mRNAs, lncRNAs, and miRNAs comparison in Yili geese. CeRNA regulatory network was constructed for key genes screening. A total of 337, 1136, and 525 differentially expressed DE mRNAs, 466, 925, and 742 DE lncRNAs and 258, 1131 and 909 DE miRNAs were identified between PP and LP, between CP and LP, and between CP and PP groups, respectively. Functional enrichment analysis showed that the differentially expressed mRNAs and non-coding RNA target genes were mainly involved in the cell process, cytokine-cytokine receptor interaction, phagosome, calcium signaling pathway, steroid biosynthesis and ECM-receptor interaction. Differential genes and non-coding RNAs, PDGFRB, ERBB4, LHCGR, MSTRG.129094.34, MSTRG.3524.1 and gga-miR-145-5p, related to reproduction and ovarian development were highly enriched. Furthermore, lncRNA-miRNA-mRNA regulatory networks related to ovary development were constructed. Our study found dramatic transcriptomic differences in ovaries of Yili geese at different egg-laying stages, and a differential lncRNA-miRNA-mRNA regulatory network related to cell proliferation, differentiation and apoptosis and involved in stromal follicle development were established and preliminarily validated, which could be regarded as a key regulatory pathway of ovarian development in Yili geese.


Knee injuries in tennis.
Racquet sports involve sharp, side-to-side movements and impose significant valgus and rotatory stresses on the knee. Most knee injuries are indirect as a result of these acute stresses and overuse. Some of the more common racquet sport injuries include tennis leg, jumper's knee, patello-femoral pain, meniscal injuries, bursitis, and tendinitis.


Regulation of proline metabolism, AsA-GSH cycle, cadmium uptake and subcellular distribution in Brassica napus L. under the effect of nano-silicon.
Cadmium (Cd) is known to have detrimental effects on plant growth and human health. Recent studies showed that silicon nanoparticles (SNPs) can decrease Cd toxicity in plants. Therefore, a study was conducted using 50 μM Cd and 1.50 mM SNPs to investigate Cd uptake, subcellular distribution, proline (Pro) metabolism, and the antioxidant defense system in rapeseed seedlings. In this study, results indicated that Cd stress negatively affected rapeseed growth, and high Cd contents accumulated in both shoots and roots. However, SNPs significantly decreased Cd contents in shoots and roots. Moreover, substantial increases were found in root fresh weight by 40.6% and dry weight by 46.6%, as well as shoot fresh weight by 60.1% and dry weight by 113.7% with the addition of SNPs. Furthermore, the addition of SNPs alleviated oxidative injury by maintaining the ascorbate-glutathione (AsA-GSH) cycle and increased Pro biosynthesis which could be due to high activities of Δ1-pyrroline-5-carboxylate synthase (P5CS) and reductase (P5CR) and decreased proline dehydrogenase (ProDH) activity. Furthermore, the addition of SNPs accumulated Cd in the soluble fraction (42%) and cell wall (45%). Results indicate that SNPs effectively reduce Cd toxicity in rapeseed seedlings which may be effective in promoting both rapeseed productivity and human health preservation.


Prevalence of and risk factors for lifetime suicide attempts among Caribbean people in the French West Indies.
It has been suggested that Black people show lower suicidality than White people. The few conflicting studies estimating lifetime prevalence of suicide attempts in Caribbean populations were mainly carried out in the UK and the USA. Our aim was to investigate the prevalence of lifetime suicide attempts among the French Caribbean general population still living in the West Indies. As part of an international epidemiological multicenter study under the authority of the World Health Organization French Collaborating Centre, we interviewed 887 individuals selected from the general population in the Caribbean island of Martinique, using the Mini International Neuropsychiatric Interview. Among the interviewed individuals, 4.4% (N=39) reported having attempted suicide. Younger age, lifetime diagnoses of major mood disorder, panic disorder and alcohol dependence were all associated with a lifetime history of suicide attempts. Lifetime prevalence of suicide attempts among the French Caribbean general population was almost half as much as that measured in continental France.


Association of MBL2 gene exon 1 variants with autoimmune thyroid disease in Brazilian patients.
We investigated the association between MBL2 gene exon 1 functional polymorphisms and autoimmune thyroid disease (AITD) in 163 Brazilian patients (87 with Hashimoto thyroiditis, HT; 76 with Graves' disease) and 214 healthy controls. Individuals carrying MBL2 O allele are at higher risk of developing AITD (OR = 1.58, 95% CI: 1.11-2.26; P-value = 0.009) and HT (OR = 1.67, 95% CI: 1.09-2.55; P-value = 0.013) as suggesting a possible role for mannose-binding lectin in influencing disease susceptibility.


Fibroblast-keratinocyte interactions in psoriasis: failure of psoriatic fibroblasts to stimulate keratinocyte proliferation in vitro.
We have tested in two ways the hypothesis that dermal fibroblasts direct the hyperproliferation of the overlying epidermis in psoriasis. First, culture medium from psoriatic and from normal skin fibroblasts was added to monolayer cultures of foreskin keratinocytes. Second, psoriatic and normal fibroblasts embedded in hydrated collagen lattices were co-cultured with monolayers of foreskin keratinocytes. There was no evidence in either study that psoriatic fibroblast products could stimulate the proliferation of the keratinocytes, or that normal fibroblast products inhibited their proliferation. A positive control for the fibroblasts was provided by leucocyte supernatants, which stimulated keratinocyte proliferation by up to 65%. Our data do not support a primary role for dermal fibroblasts in psoriasis.


Implementing early mobilisation after knee or hip arthroplasty to reduce length of stay: a quality improvement study with embedded qualitative component.
Models of care for managing total knee or hip arthroplasty (TKA, THA) incorporating early mobilisation are associated with shorter acute length-of-stay (LOS). Few studies have examined the effect of implementing early mobilisation in isolation, however. This study aimed to determine if an accelerated mobilisation protocol implemented in isolation is associated with a reduced LOS without undermining care. A Before-After (quasi-experimental) study was used. Standard practice pre-implementation of the new protocol was physiotherapist-led mobilisation once per day commencing on post-operative Day 1 (Before phase). The new protocol (After phase) aimed to mobilise patients four times by end of Day 2 including an attempt to commence on Day 0; physiotherapy weekend coverage was necessarily increased. Poisson regression modelling was used to determine associations between study period and LOS. Additional outcomes to 12 weeks post-surgery were monitored to identify unintended consequences of the new protocol. Time to first mobilisation (hours) and proportion mobilising Day 0 were monitored to assess protocol compliance. An embedded qualitative component captured staff perspectives of the new protocol. Five hundred twenty consecutive patients (n = 278, Before; n = 242, After) were included. The new protocol was associated with no change in unadjusted LOS, a small reduction in adjusted LOS (8.1%, p = 0.046), a reduction in time to first mobilisation (28.5 (10.8) vs 22.6 (8.1) hrs, p < 0.001), and an increase in the proportion mobilising Day 0 (0 vs 7%, p < 0.001). Greater improvements were curtailed by an unexpected decrease in physiotherapy staffing (After phase). There were no significant changes to the rates of complications or readmissions, joint-specific pain and function scores or health-related quality of life to 12 weeks post-surgery. Qualitative findings of 11 multidisciplinary team members highlighted the importance of morning surgery, staffing, and well-defined roles. Small reductions in LOS are possible utilising an early mobilisation protocol in isolation after TKA or THA although staff burden is increased likely undermining both sustainability and the magnitude of the change. Simultaneous incorporation of other changes within the pathway would likely secure larger reductions in LOS.


Minocycline Attenuates Iron-Induced Brain Injury.
Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.


Selective loss of chromosome 11 in pheochromocytomas associated with the VHL syndrome.
By using comparative genomic hybridization (CGH), we characterized the genetic profiles of 36 VHL-related pheochromocytomas. We then compared the results with those of sporadic and MEN 2-related pheochromocytomas. In 36 VHL-related tumors, loss of chromosome 3 and chromosome 11 were found in 34 tumors (94%) and 31 tumors (86%), respectively. There was significant concordance of deletions in chromosomes 3 and 11 (Kappa=0.64, P=0.0095), suggesting that they are involved in two different but necessary and complementary genetic pathways. The loss of chromosome 11 appeared to be specific for VHL-related pheochromocytoma as it was not present in any of the 10 VHL-related CNS hemangioblastomas studied and was significantly less common when compared with (a) sporadic pheochromocytomas from previously published results (13%; P=<0.0001), and (b) MEN 2-related pheochromocytomas from this and previously published studies (30%; P=0.0012). In summary, this is the first report of a novel consistent genetic alteration that is selected and specific for VHL-related pheochromocytoma, besides the two hits of the VHL gene.


Entropy generation minimization (EGM) in magneto peristalsis with variable properties.
This article featuring the peristaltic transport of viscous material with variable properties (i.e. temperature dependent viscosity and thermal conductivity) through curved configuration. Fluid saturating through porous channel walls of uniform space. Entropy generation consideration here is to analyze irreversibility aspects. Channel boundaries retain the velocity and thermal slip conditions. Wave frame of reference is attained with the utilization of long wavelength and small Reynolds number approach. Solution of the simplified coupled system of dimensionless constraints is obtained numerically. Detailed analysis of important quantities of interest has been presented in discussion portion. Entropy generation variation near center is very small whereas in the vicinity of the channel wall is larger. Bejan number has reverse variation as observed for entropy generation. Variable characteristics of viscosity has opposite impact on velocity and temperature is observed. It is also noticed small irreversibility effects are obtained for higher varying viscosity and thermal conductivity near the vicinity of the channel walls.


Ultraviolet-mediated cytotoxic activity of phenylheptatriyne from Bidens pilosa L.
The tropical weed Bidens pilosa L. (Asteraceae) contains a number of polyacetylenes which are phototoxic to bacteria, fungi, and human fibroblast cells in the presence of sunlight, artificial sources of long-wave ultraviolet light, or cool-white fluorescent light. The principle photoactive compound in the leaf, phenylheptatriyne, is present in the cuticle as well as in the underlying cells. Experiments with calf thymus DNA indicate that, unlike photoactive furanocoumarins, phenylheptatriyne does not form interstrand cross linkages with DNA in ultraviolet light.


The Covid-19 outbreak, corporate financial distress and earnings management.
This study explores the association between the Covid-19 outbreak, corporate financial distress and earnings management practices in China. We investigate whether firms took advantage of the downturn in economic conditions during the pandemic to adjust their earnings using different earnings management techniques. Utilising a sample of 1832 listed firms and underlying theoretical frameworks (i.e., positive accounting and signalling theory), we find that firms were more inclined to manage earnings during the pandemic period. They favoured using the accrual-based rather than the real activity-based earnings management technique. We also find that firms engaged more in income-increasing practices in the shadow of the outbreak. In addition, our results further demonstrate that financially distressed firms were involved in earnings management, particularly accrual-based earnings management. However, compared to privately-owned firms, state-owned enterprises seem to be involved less in earnings management during the Covid-19 pandemic. Findings from this study raise some concerns for policymakers about the credibility of financial reporting information during Covid-19.


Refugee stress and folk belief: Hmong sudden deaths.
Since the first reported death in 1977, scores of seemingly healthy Hmong refugees have died mysteriously and without warning from what has come to be known as Sudden Unexpected Nocturnal Death Syndrome (SUNDS). To date medical research has provided no adequate explanation for these sudden deaths. This study is an investigation into the changing impact of traditional beliefs as they manifest during the stress of traumatic relocation. In Stockton, California, 118 Hmong men and women were interviewed regarding their awareness of and personal experience with a traditional nocturnal spirit encounter. An analysis of this data reveals that the supranormal attack acts as a trigger for Hmong SUNDS.


Age Differences in the Experience of Daily Life Events: A Study Based on the Social Goals Perspective.
This study examined age differences in daily life events related to different types of social goals based on the socioemotional selectivity theory (SST), and determined whether the positivity effect existed in the context of social goals in older adults' daily lives. Over a course of 14 days, 49 older adults and 36 younger adults wrote about up to three life events daily and rated the valence of each event. The findings indicated that (1) although both older and younger adults recorded events related to both emotional and knowledge-acquisition goals, the odds ratio for reporting a higher number of events related to emotional goals compared to the number of events related to knowledge-acquisition goals was 2.12 times higher in older adults than that observed in younger adults. (2) Considering the number of events, there was an age-related positivity effect only for knowledge-related goals, and (3) older adults' ratings for events related to emotional and knowledge-acquisition goals were significantly more positive compared to those observed in younger adults. These findings supported the SST, and to some extent, the positivity effect was demonstrated in the context of social goals.


Automated SPME-GC-MS monitoring of headspace metabolomic responses of E. coli to biologically active components extracted by the coating.
Monitoring extracellular metabolites of bacteria is very useful for not only metabolomics research but also for assessment of the effects of various chemicals, including antimicrobial agents and drugs. Herein, we describe the automated headspace solid-phase microextraction (HS-SPME) method coupled with gas chromatography-mass spectrometry (GC-MS) for the qualitative as well as semi-quantitative determination of metabolic responses of Escherichia coli to an antimicrobial agent, cinnamaldehyde. The minimum inhibitory concentration of cinnamaldehyde was calculated to be 2 g L(-1). We found that cinnamaldehyde was an important factor influencing the metabolic profile and growth process. A higher number of metabolites were observed during the mid-logarithmic growth phase. The metabolite variations (types and concentrations) induced by cinnamaldehyde were dependent on both cell density and the dose of cinnamaldehyde. Simultaneously, 25 different metabolites were separated and detected (e.g., indole, alkane, alcohol, organic acids, esters, etc.) in headspace of complex biological samples due to intermittent addition of high dose of cinnamaldehyde. The study was done using an automated system, thereby minimizing manual workup and indicating the potential of the method for high-throughput analysis. These findings enhanced the understanding of the metabolic responses of E. coli to cinnamaldehyde shock effect and demonstrated the effectiveness of the SPME-GC-MS based metabolomics approach to study such a complex biological system.


Sequence of inverted terminal repetitions from different adenoviruses: demonstration of conserved sequences and homology between SA7 termini and SV40 DNA.
We have established the nucleotide sequence for the inverted terminal repetition of human adenovirus type 3, a subgroup B adenovirus. The repetition, which is 136 bp long, shows a high degree of homology with the known sequence for the inverted repetition of adenovirus type 5 (Steenbergh et al., 1977) a subgroup C adenovirus. Partial sequence information convering 120 bp of the inverted terminal repetitions of human serotype 12, a subgroup A member, and of simian adenovirus type 7 has also been obtained. A comparison of the established sequences shows that the terminal repetitions, in particular the first 50 bp from the ends, contain sequences that have been well conserved in adenovirus evolution. For instance, only six mismatched base pairs were detected among the first 50 bp in the repetitions of simian adenovirus type 7 and human adenovirus type 5, although the homology between simian adenovirus 7 and human subgroup C adenoviruses was estimated to be only 30%. A 14 bp sequence located 9-22 nucleotides from the ends is present in DNAs from all the human serotypes examined as well as in simian adenovirus 7 DNA. Furthermore, the simian adenovirus 7 repetition contains a 21 bp sequence which is present in SV40 DNA, close to the origin of DNA replication.


Long-term decentration of intraocular lenses implanted with envelope capsulotomy and continuous curvilinear capsulotomy: a comparative study.
Intraocular lens (IOL) decentration was studied in a series of 569 consecutive eyes that had extracapsular cataract extraction (ECCE) and posterior chamber IOL implantation. In 383 of the eyes, an envelope capsulotomy (EC) was performed; in 186, a continuous curvilinear capsulotomy (CCC). In 33 eyes, the anterior capsule had one radial tear that reached the lens equator. In all eyes, IOL decentration was determined more than six months after surgery. Mean IOL decentration was 0.42 +/- 0.02 mm in the EC eyes and 0.27 +/- 0.01 mm in the CCC eyes (P < .001). In the CCC eyes, mean IOL decentration was 0.23 +/- 0.02 mm when the anterior capsule had no tears and 0.42 +/- 0.06 mm when it had one radial tear (P < .01). In the EC eyes, mean decentration was less with lenses with a total diameter of 11.0 mm or less and 360 degree circular loops (compressible disc and circular open-loop lenses) than with C- and J-loop lenses with a total length of 13.5 mm to 14.0 mm. With the C- and J-loop lenses in all three capsulotomy groups, mean decentration was related to the presence and number of tears in the anterior capsule: 0.58 mm in the EC eyes, 0.41 mm in the CCC with tear eyes, and 0.23 mm in the CCC without tear eyes. A similar relationship was seen with the bag-implanted lenses: 0.48 mm in the EC eyes, 0.28 mm in the CCC with tear eyes; 0.22 mm in the CCC without tear eyes.


The recovery of phosphorus from source-separated urine by repeatedly usable magnetic Fe3O4@ZrO2 nanoparticles under acidic conditions.
The separation of urine at source for phosphorus (P) recovery is attractive taking into account the high P concentration and small volume. However, the treatment of urine is still challenging due to its unpleasant odor and hygiene problems. Because the above problems could be solved by acidification to keep the pH of urine below 4, we propose a novel strategy to recover P from acidified urine using tailored hydrous zirconia-coated magnetite nanoparticles (Fe3O4@ZrO2). This strategy involves the selective adsorption of phosphate by easily separable and reusable Fe3O4@ZrO2, the desorption of adsorbed phosphate, and the precipitation of desorbed phosphate as calcium phosphate fertilizer. The results indicated that at pH 4, the P in synthetic urine was selectively adsorbed and could be exhausted using Fe3O4@ZrO2. Nearly all (>97.5%) of the sequestered P on the Fe3O4@ZrO2 nanoparticles was stripped using ≥1 M NaOH solution and ~100% of the stripped P was then successfully transformed into calcium phosphate, upon adding CaCl2 at pH >12 and a Ca/P molar ratio of 3. The liquid/solid (Fe3O4@ZrO2 particles) mixture could be conveniently separated for reuse using an external magnetic field. The reusability of the Fe3O4@ZrO2 nanoparticles in the extraction of P from synthetic urine was confirmed using five cycles of the adsorption-desorption process and their performance validated using real urine samples. The mechanism of phosphate adsorption was investigated using XPS, FTIR and zeta potential measurements, showing that phosphate was chemically adsorbed on the surface through direct coordination to zirconium atom via ligand exchange.


Impaction autografting: bone-preserving, secure fixation of a standard humeral component.
When fixed with bone ingrowth, a tight diaphyseal press fit, or cement, the humeral component of a shoulder arthroplasty may present problems of malposition, stress shielding, or periprosthetic fracture or difficulty with removal at revision arthroplasty. We have avoided the need for these fixation methods by using impaction cancellous autografting of the humeral stem, minimizing contact between the prosthetic stem and the humeral cortex. This study presents the radiographic survivorship of impaction-autografted humeral implants using component subsidence as the primary endpoint. We reviewed 286 primary anatomic shoulder arthroplasties having an average follow-up of 4.9 ± 2.7 years. Initial postoperative radiographs and minimum 2-year follow-up radiographs were evaluated by 3 observers to assess subsidence. Two different implants (Humeral Replacement Prosthesis [HRP] and Global Advantage prosthesis) were used. Of 286 stems, 267 (93.4%) had not subsided. The Global Advantage prosthesis had a subsidence-free survival rate of 98.5% at 5 years. The stiffer-stemmed HRP used early during the study had a higher rate of subsidence compared with the currently used Global Advantage stem (hazard ratio, 5.6; P = .001). Radiolucent lines of 2 mm or greater were less common for the Global Advantage prosthesis than for the HRP in each of 7 zones (P < .001). Total shoulder arthroplasty was associated with a higher rate of subsidence compared with hemiarthroplasty (hazard ratio, 2.6; P = .12). Impaction autografting provides a secure, durable, bone-preserving means of humeral component fixation in anatomic shoulder arthroplasty.


Removal of covalently bound inositol from Torpedo acetylcholinesterase and mammalian alkaline phosphatases by deamination with nitrous acid. Evidence for a common membrane-anchoring structure.
Our earlier evidence suggested that both acetylcholinesterase and alkaline phosphatase are anchored to the cell surface via covalently-attached phosphatidylinositol [Low, Futerman, Ferguson & Silman (1986) Trends Biochem. Sci. 11, 212-215]. We now present chemical data, based upon a nitrous acid deamination reaction, showing that in both proteins the phosphatidylinositol moiety is attached through a glycosidic linkage to a sugar residue bearing a free amino group.


First report of mandibular ramus fracture associated with anterior dislocation of ipsilateral condyle into temporal fossa and locked jaw: A Rarity.
Mandibular ramus fracture is the second least common variant of fracture of mandible. Recently there has been an upsurge in the incidence of ramus fracture due to high velocity road traffic accidents. Ramus fracture is mostly seen in association with other mandibular fracture. This is the first report of mandibular ramus fracture associated with anterior dislocation of ipsilateral condyle into temporal fossa which was treated successfully under local anaesthesia by closed reduction.


Gender Diversity in Sports Medicine: Current Trends.
As the sports medicine field has grown, the need for a more diverse workforce has become more evident. Given the growing athlete diversity that exists at all recreational and competitive levels of organized sports, it is important to better understand the current state of athletic health care diversity. This review assesses the current state of diversity in sports medicine from the perspective of the medical and athletic training professions. Men and women currently display nearly equivalent participation levels; however, the distribution of female team physicians and athletic trainers could better match the teams that they serve. Although progress has been made, much more needs to be done to bring more female athletic trainers and team physicians into athletic health care leadership roles. Early mentoring programs have shown efficacy for increasing the number of female candidates who might become the foundation of future athletic health care and academic program leaders. V, expert opinion.


Kinetic constants for uptake and metabolism of 3H-(-)noradrenaline in rabbit aorta. Possible falsification of the constants by diffusion barriers within the vessel wall.
1. The neuronal uptake of 3H-(-)noradrenaline into aortic rings from reserpine-pretreated animals was a saturable process with a Km of 2.3 mumol X l-1 and a Vmax of 0.5 nmol X g-1 X min-1. Similar constants were obtained when the neuronal deamination of noradrenaline was taken as an index for neuronal uptake. When the tissue was incubated in the usual way, i.e., when the amine was allowed to enter the aortic rings via both the intimal and the adventitial surface, then there was no initial delay (tlag) for the neuronal uptake of noradrenaline (MAO and COMT inhibited). On the other hand, when the amine entry was restricted to the intimal surface, there was a tlag of 2 min, probably due to the slow equilibration of the extracellular space of the media with the incubation medium. Furthermore, for low amine concentrations the rate of uptake in the latter situation was about 10 times lower than that in the former one. Thus, the rate of uptake clearly depended on the way the amine entered the tissue. 2. The corticosterone-sensitive extraneural uptake of 3H-(-)noradrenaline determined in nerve-free aortic rings was characterised by a high Km (490 mumol X l-1) and Vmax (35 nmol X g-1 X min-1). For uptake2 a tlag of 1 min was observed. 3. The analysis of the extraneuronal O-methylating system in nerve-free aortic rings yielded a Km of 3.6 mumol X l-1 and a Vmax of 0.6 nmol X g-1 X min-1. The tlag for the O-methylation of noradrenaline was in the same order of magnitude as that for uptake2. At low amine concentrations the corticosterone-sensitive accumulation of noradrenaline was prevented by COMT, but not by MAO. The latter enzyme reduced the steady-state accumulation of noradrenaline by about 50%. When the amine entry was restricted to one surface only, the results indicated that the extraneuronal O-methylation of noradrenaline generated a steep concentration gradient of the parent amine within the extracellular space of the aorta. 4. All saturable processes fitted the Michaelis-Menten equation. However, kinetic constants determined in incubated organs may be falsified by poor diffusion of the substrate through the extracellular space.


Identification of cell division cycle protein 20 in various forms of acute and chronic kidney injury in mice.
Tubular epithelial cell fate following exposure to various types of injurious stimuli can be decided at distinct cell cycle checkpoints. One such checkpoint occurs during mitosis, known as the spindle assembly checkpoint, and is tightly regulated through the actions of cell division cycle protein 20 (CDC20). Due to our paucity of knowledge about the role of CDC20 in the kidney, the present study was designed to investigate the expression levels and distribution of CDC20 within the kidney and how pharmacological inhibition of CDC20 function affects kidney recovery using various rodent models of kidney injury. CDC20 is normally detected in distal tubules, but upon injury by either cisplatin administration or ureter obstruction, CDC20 accumulation is considerably elevated. Blockade of CDC20 activity using a selective pharmacological inhibitor, Apcin, lowered serum creatinine, tubular damage, and DNA injury following acute kidney injury compared with vehicle-treated mice. In unilateral ureteral obstruction, Apcin reduced tissue kidney injury molecule-1 levels, sirius red staining, and tubulointerstitial α-smooth muscle actin staining in the tissue. The findings in the present study demonstrated that elevations in CDC20 levels in the kidney are associated with kidney injury and that inhibition of CDC20 can alleviate and reverse some of the pathological effects on the architecture and function of kidney.NEW & NOTEWORTHY To our knowledge, this is the first study to characterize the expression and localization of cell division cycle 20 protein (CDC20) in normal and acute, and chronically injured kidneys. Tubular epithelial cell damage was markedly reduced through the administration of a selective inhibitor of CDC20, Apcin. This study provides new evidence that CDC20 can be induced in damaged kidney cells and negatively impact the recovery of the kidney following acute kidney injury.


Rosiglitazone/Metformin.
The thiazolidinedione rosiglitazone and the biguanide metformin are effective antihyperglycaemic agents with different modes of action; rosiglitazone primarily increases insulin sensitivity, whereas metformin primarily reduces hepatic glucose output. Antihyperglycaemic combination therapy is often required to achieve effective glycaemic control. A fixed-dose formulation of rosiglitazone/metformin was recently approved in the EU and the US for the treatment of type 2 diabetes mellitus in patients inadequately controlled on metformin monotherapy. Bioequivalence between the fixed-dose combination tablet and coadministration of rosiglitazone with metformin at the same dosage has been established in a pharmacokinetic study. Fixed-dose rosiglitazone/metformin 8 mg/2g per day reduced glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels to a significantly greater extent than metformin 3 g/day in patients with type 2 diabetes in a 24-week, randomised, double-blind study. Rosiglitazone plus metformin was significantly more effective than metformin alone at reducing HbA1c and FPG levels in patients with type 2 diabetes in three 26-week, randomised, double-blind, placebo-controlled studies. Rosiglitazone plus metformin was generally well tolerated in all studies and had a tolerability profile similar to that of metformin monotherapy. Mild or moderate symptomatic hypoglycaemia was reported in <or=4.4% of rosiglitazone plus metformin recipients.


Pulse repetition rate increases the minimum threshold and latency of auditory neurons.
The effect of pulse repetition rate on auditory sensitivity of the big brown bat, Eptesicus fuscus, was studied by determining the minimum threshold, response latency and recovery cycle of inferior collicular neurons at different repetition rates under free field stimulation conditions. In general, collicular neurons shortened the response latency and increased the number of impulses monotonically or non-monotonically with stimulus intensity. They recovered at least 50% when the interpulse interval was 10-57 ms. In addition, they increased the minimum threshold, lengthened the response latency, and reduced the number of impulses discharged to each pulse with increasing repetition rate. The increase in minimum threshold with repetition rate is partly because the neuron can not recover from previous stimulation when the interpulse interval is shortened. This increase reduces a neuron's response sensitivity and thus diminishes its number of impulses to each presented pulse. This increase also reduces the effectiveness of a given stimulus intensity which contributes to the lengthening of the neuron's response latency. Data obtained from single neuron recordings are used to highlight these observations. Implications of present findings regarding the bat's echolocation are also discussed.


Ultrasound for the detection of the pyramidal lobe of the thyroid gland.
The pyramidal lobe (PL) is an ancillary lobe of the thyroid gland that can be affected by the same pathologies as the rest of the gland. We aimed to assess the diagnostic performance of high-resolution sonography in the detection of the PL with verification by dissection and histological examination. In a prospective, cross-sectional mono-center study, 50 fresh, non-embalmed cadavers were included. Blinded ultrasound examination was performed to detect the PL by two investigators of different experience levels. If the PL was detected with ultrasound, dissection was performed to expose the PL and obtain a tissue sample. When no PL was detected with ultrasound, a tissue block of the anterior cervical region was excised. An endocrine pathologist microscopically examined all tissue samples and tissue blocks for the presence of thyroid parenchyma. The prevalence of the PL was 80% [40/50; 95% CI (68.9%; 91.1%)]. Diagnostic performance for both examiners was: sensitivity (85.0%; 42.5%), specificity (50.0%; 60.0%), positive predictive value (87.2%; 81.0%), negative predictive value (45.5%; 21.0%) and accuracy (78.0%; 46.0%). Regression analysis demonstrated that neither thyroid parenchyma echogenicity, thyroid gland volume, age nor body size proved to be covariates in the accurate detection of a PL (p > .05). We report that high-resolution ultrasound is an adequate examination modality to detect the PL. Our findings indicate a higher prevalence than previously reported. Therefore, the PL may be regarded as a regular part of the thyroid gland. We also advocate a dedicated assessment of the PL in routine thyroid ultrasound.


New-onset sensory loss or alteration.
New-onset sensory loss often poses a problem for emergency physicians because of the vast array of potential causes for this condition and the imprecision patients display in explaining their condition. This article reviews potential causes of particular interest to the emergency physician and illustrates approaches to sensory alteration complaint with case studies.


Posterior clearance increases the knee extension angle in cruciate retaining type total knee arthroplasty: Intraoperative evaluation using a navigation system.
Posterior osteophyte of the femur can impinge on the tibia insert in total knee arthroplasty (TKA). Although osteophyte removal [posterior clearance (PC)] improves the flexion angle, its influence on the gaps and extension angle are unclear. This study investigated the effect of PC on the gaps and range of motion (ROM) using a navigation system, as well as PC's relationship with osteophyte size. Twenty-seven knees that underwent cruciate-retaining (CR)-type TKA were examined. Before and after PC, the ROM, hip-knee-ankle (HKA) angle, and flexion and extension gaps were recorded using a navigation system. Osteophyte size was measured in the lateral view in radiographs, and in the sagittal and axial planes of computed tomography (CT) images. The effects of PC on the gaps and ROM were analysed statistically. PC caused the extension gap to increase by 0.7 ± 0.9 mm in the medial (p < 0.001), and 0.9 ± 1.5 mm in the lateral compartment (p = 0.006). The extension angle increased by 4.9 ± 1.6°, flexion angle increased by 6.5 ± 5.0°, and HKA decreased by 0.3°. The increase in extension angle by PC was significantly correlated with the preoperative HKA angle (r = 0.594) and with the osteophyte area in radiographs and CT (r = 0.626 to 0.681). The extension and flexion gaps increased less than 1 mm in the medial and lateral compartments. PC achieving an additional 5° extension angle could promote full extension in severely deformed knees with a large posterior osteophyte. The extension angle increase by PC was correlated with the preoperative HKA angle and osteophyte size.


Volumetric Analysis of Progressive Remodeling of Isolated Mesenteric Artery Dissection Treated by Conservative Therapy.
To characterize remodeling of conservatively treated isolated mesenteric artery dissection (IMAD) using 3-dimensional (3D) volumetric analysis. Patients with Type I/II (classification of Yun) treated by conservative therapy between January 2018 and January 2020 were prospectively included. Semiautomatic morphological analysis of the superior mesenteric artery (SMA) included volumetric measurements of the true lumen (TL), false lumen (FL), and overall lumen (OL) and 3D aortomesenteric angles from computed tomography angiography data at admission (T0), 1 month (T1), and 12 months (T12). The SMA morphology of patients with IMAD (n = 15, mean age 53 years ± 7; 87% men) was also compared with that of control individuals (n = 51, mean age 56 years ± 4; 94% men). A significant reduction in OL volume was observed (P <.001), whereas TL volume remained stable (P =.23). The TL/OL volume ratio significantly increased over time (P =.001) from 53% at T1 to 78% at T12. Aortomesenteric 3D angles at 2, 4, and 6 cm from the ostium showed a progressive decrease toward values observed in the control group (P =.013, P =.002, and P =.027, respectively). At T12, 5 patients (33%) had complete remodeling, and aneurysmal change was observed in 2 patients (<20 mm). Smoking and SMA angle at a distance of 6 cm from the ostium (T0) were the only factors affecting remodeling negatively at T12. One-year remodeling in IMAD followed an overall decrease in OL volume related to a decrease in FL volume. Smokers and patients with larger SMA angles at baseline showed poorer remodeling. Spontaneous arterial remodeling in IMAD might favor conservative therapy.


Patients' silence following healthcare staff's ethical transgressions.
The aim of this study was to examine to what extent patients remained silent to the health care system after they experienced abusive or wrongful incidents in health care. Female patients visiting a women's clinic in Sweden (n = 530) answered the transgressions of ethical principles in Health care questionnaire (TEP), which was constructed to measure patients' abusive experiences in the form of staff's transgressions of ethical principles in health care. Of all the patients, 63.6% had, at some point, experienced staff's transgressions of ethical principles, and many perceived these events as abusive and wrongful. Of these patients, 70.3% had remained silent to the health care system about at least one transgression. This silence is a loss of essential feedback for the health care system and should not automatically be interpreted as though patients are satisfied.


Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge.
The genetic diversity of the three Southern African Territories (SAT) types of foot-and-mouth disease virus (FMDV) reflects high antigenic variation, and indications are that vaccines targeting each SAT-specific topotype may be needed. This has serious implications for control of FMD using vaccines as well as the choice of strains to include in regional antigen banks. Here, we investigated an intra-serotype chimeric virus, vSAT2(ZIM14)-SAT2, which was engineered by replacing the surface-exposed capsid-coding region (1B-1D/2A) of a SAT2 genome-length clone, pSAT2, with that of the field isolate, SAT2/ZIM/14/90. The chimeric FMDV produced by this technique was viable, grew to high titres and stably maintained the 1B-1D/2A sequence upon passage. Chemically inactivated, oil adjuvanted vaccines of both the chimeric and parental immunogens were used to vaccinate cattle. The serological response to vaccination showed the production of strong neutralizing antibody titres that correlated with protection against homologous FMDV challenge. We also predicted a good likelihood that cattle vaccinated with an intra-serotype chimeric vaccine would be protected against challenge with viruses that caused recent outbreaks in southern Africa. These results provide support that chimeric vaccines containing the external capsid of field isolates induce protective immune responses in FMD host species similar to the parental vaccine.


Long-term effect of low-density lipoprotein apheresis in patients with heterozygous familial hypercholesterolemia.
Clinical efficacy and safety of the therapeutic tool which directly removes LDL particles from circulation (LDL apheresis) have already been established in the treatment for refractory hypercholesterolemia in patients with familial hypercholesterolemia (FH). Two clinical studies with event-based assessment have demonstrated remarkably beneficial outcomes of long-term LDL apheresis using dextran sulfate cellulose columns plus adjunctive cholesterol-lowering drug therapy in the prevention of cardiovascular events in heterozygous FH with coronary artery disease. The results of several studies with angiographic and ultrasound-based assessment indicate a possible role for LDL apheresis in restructuring and stabilization of atherosclerotic lesions. These clinical improvements caused by LDL apheresis in heterozygous FH support the efficacy and importance of aggressive cholesterol-lowering therapy for secondary prevention of atherosclerotic cardiovascular disease in hypercholesterolemic patients.


A trial of the in vitro sensitivity test of anti-cancer drugs using primary cultured urogenital cancer cells.
An in vitro chemosensitivity test was applied to clinical specimens of urogenital cancer tissues obtained at operation. Incorporation of 3H-leucine into primary cultured cells 24 h after treatment with cytotoxic drugs was used as an index for cell viability. Primary cell culture was performed using specimens obtained from 37 patients including 20 with transitional cell carcinoma, 15 with renal cell carcinoma and 2 with testicular cancer. Primary cell growth was achieved in 27 (73%) out of 37 specimens and 10 were tested for chemosensitivity. Each specimen of the tumor revealed different sensitivity to drugs, and results of quadruplicate tests for each specimen were identical. It was concluded that the present method of measuring incorporation of radioactivity using urogenital cancer cells primarily cultured in microtiter plate is practically applicable to an in vitro chemosensitivity test.


Forecasting of daily air quality index in Delhi.
As the impact of air pollutants on human health through ambient air address much attention in recent years, the air quality forecasting in terms of air pollution parameters becomes an important topic in environmental science. The Air Quality Index (AQI) can be estimated through a formula, based on comprehensive assessment of concentration of air pollutants, which can be used by government agencies to characterize the status of air quality at a given location. The present study aims to develop forecasting model for predicting daily AQI, which can be used as a basis of decision making processes. Firstly, the AQI has been estimated through a method used by US Environmental Protection Agency (USEPA) for different criteria pollutants as Respirable Suspended Particulate Matter (RSPM), Sulfur dioxide (SO2), Nitrogen dioxide (NO2) and Suspended Particulate Matter (SPM). However, the sub-index and breakpoint concentrations in the formula are made according to Indian National Ambient Air Quality Standard. Secondly, the daily AQI for each season is forecasted through three statistical models namely time series auto regressive integrated moving average (ARIMA) (model 1), principal component regression (PCR) (model 2) and combination of both (model 3) in Delhi. The performance of all three models are evaluated with the help of observed concentrations of pollutants, which reflects that model 3 agrees well with observed values, as compared to the values of model 1 and model 2. The same is supported by the statistical parameters also. The significance of meteorological parameters of model 3 has been assessed through principal component analysis (PCA), which indicates that daily rainfall, station level pressure, daily mean temperature, wind direction index are maximum explained in summer, monsoon, post-monsoon and winter respectively. Further, the variation of AQI during the weekends (holidays) and weekdays are found negligible. Therefore all the days of week are accounted same in the models.


Characterization and chromosomal mapping of a novel human gene, ANKHZN.
Ankhzn (ankyrin repeats hooked to a zinc finger motif) was originally isolated by means of the gene trap method, as a novel cytoplasmic protein on mouse embryonic stem cells. The Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. In the present study, we have cloned human ANKHZN cDNA by PCR using candidate EST clones exhibiting a high homology to mouse Ankhzn cDNA. The human ANKHZN cDNA encoded a 1166aa protein exhibiting 84.9% identity to the mouse one. The size of the transcript was found to be about 7kb on a Northern blot analysis, and ANKHZN mRNA was found to be ubiquitously expressed in human tissues on RT-PCR analysis. Western blot analysis showed that a 130kDa protein was detected at various levels in human tissues and also present in both membrane and soluble fractions obtained on subcellular fractionation. Human ANKHZN is a single copy gene consisting of predicted 25 exons in the human genome, and has been mapped to human chromosome 17p13 by radiation hybrid panel and fluorescence in-situ hybridization.


Emergent cholecystectomy in patients on antithrombotic therapy.
The Tokyo Guidelines 2018 (TG18) recommend emergent cholecystectomy (EC) for acute cholecystitis. However, the number of patients on antithrombotic therapy (AT) has increased significantly, and no evidence has yet suggested that EC should be performed for acute cholecystitis in such patients. The aim of this study was to evaluate whether EC is as safe for patients on AT as for patients not on AT. We retrospectively analyzed patients who underwent EC from 2007 to 2018 at a single center. First, patients were divided into two groups according to the use of antithrombotic agents: AT; and no-AT. Second, the AT group was divided into three sub-groups according to the use of single antiplatelet therapy (SAPT), double antiplatelet therapy (DAPT), or anticoagulant with or without antiplatelet therapy (AC ± APT). We then evaluated outcomes of EC among all four groups. The primary outcome was 30- and 90- day mortality rate, and secondary outcomes were morbidity rate and surgical outcomes. A total of 478 patients were enrolled (AT, n = 123, no-AT, n = 355) patients. No differences in morbidity rate (6.5% vs. 3.7%, respectively; P = 0.203), 30-day mortality rate (1.6% vs. 1.4%, respectively; P = 1.0) or 90-day mortality rate (1.6% vs. 1.4%, respectively; P = 1.0) were evident between AT and no-AT groups. Between the no-AT and AC ± APT groups, a significant difference was seen in blood loss (10 mL vs. 114 mL, respectively; P = 0.017). Among the three AT sub-groups and the no-AT group, no differences were evident in morbidity rate (3.7% vs. 8.9% vs. 0% vs. 6.5%, respectively; P = 0.201) or 30-day mortality (1.4% vs. 0% vs. 0% vs. 4.3%, respectively; P = 0.351). No hemorrhagic or thrombotic morbidities were identified after EC in any group. In conclusion, EC for acute cholecystitis is as safe for patients on AT as for patients not on AT.


The neural regulation of the kidney in hypertension and renal failure.
What is the topic of this review? Reports that bilateral renal denervation in resistant hypertensive patients results in a long-lasting reduction in blood pressure raise the question of the underlying mechanisms involved and how they may be deranged in pathophysiological states of hypertension and renal failure. What advances does it highlight? The renal sensory afferent nerves and efferent sympathetic nerves work together to exert an important control over extracellular fluid volume, hence the level at which blood pressure is set. This article emphasizes that both the afferent and the efferent renal innervation may contribute to the neural dysregulation of the kidney that occurs in chronic renal disease and resistant hypertension. Autonomic control is central to cardiovascular homeostasis, and this is exerted not only at the level of the heart and blood vessels but also at the kidney. At the kidney, the sympathetic neural regulation of renin release and fluid reabsorption may influence fluid balance and, in the longer term, the level at which blood pressure is set. The role of the renal innervation in the regulation of blood pressure has received renewed attention over the past few years, following the reports that bilateral renal denervation of resistant hypertensive patients resulted in a marked reduction in blood pressure, which has been maintained for several years. Such has been the interest that this approach of renal denervation is being applied in other patient groups with diabetes, obesity and renal failure, with the hope that there may be a sustained reduction in blood pressure as well as the amelioration of some aspects of the metabolic syndrome. However, the factors that come into play to cause the rise in blood pressure in these patient groups, particularly the resistant hypertensive patients, are far from clear. Moreover, the mechanisms leading to the fall in blood pressure following renal denervation of resistant hypertensive patients currently elude our understanding and is therefore an area that requires much more investigation to enhance our insight.


DNase I sensitivity of Microtus agrestis active, inactive and reactivated X chromosomes in mouse-Microtus cell hybrids.
We isolated Microtus agrestis-mouse somatic cell hybrid clones which had retained either the active or the inactive M. agrestis X chromosome. In both hybrid clones the X chromosomes retained their original chromatin conformation as studied by the in situ nick translation technique--the active X chromosome retained its high sensitivity to DNase I while the inactive one remained insensitive. A clone in which the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene had been spontaneously reactivated was isolated from the hybrid containing the inactive X chromosome. The in situ nick translation technique was used to study possible DNA conformation changes in the euchromatin of the inactive X chromosome with special reference to the reactivated HPRT locus. We found that the euchromatin in this X chromosome exhibited the same low sensitivity to DNase I as is characteristic of the inactive X chromosome.


Modulation of the activity of amino acid transport system L by phorbol esters and calmodulin antagonists in a human placental choriocarcinoma cell line.
We investigated the regulation of the activity of amino acid transport system L in the JAR human placental choriocarcinoma cell line by agents which are known to modulate the activities of three different classes of protein kinases, A-kinase, C-kinase and CaM-kinase. The system L activity was measured by determining the uptake of leucine in these cells, grown as confluent monolayers. Leucine uptake in these cells was predominantly Na(+)-independent, was stimulated by lowering the extracellular pH and was inhibited by hydrophobic neutral amino acids. These characteristics demonstrate that uptake of leucine in this cell line occurs primarily via system L. Treatment of the cells with cholera toxin and forskolin, agents which are known to elevate intracellular cAMP levels, did not have any effect on the activity of system L. 4 beta-Phorbol 12-myristate 13-acetate, an activator of C-kinase, but not the inactive analogue 4 alpha-phorbol 12,13-didecanoate, caused a significant stimulation of system L. The involvement of C-kinase in the phorbol ester-induced stimulation was supported by the finding that staurosporine, an inhibitor of C-kinase, effectively blocked the stimulation. Calmodulin antagonists, calmidazolium, W-7 and CGS 9343 B stimulated system L activity markedly. The potency of these antagonists was in the following order: calmidazolium greater than CGS 9343 B greater than W-7. This stimulatory effect was specific for system L because systems A and ASC were not stimulated by these agents. The stimulation caused by these agents was primarily due to an increase in the maximal velocity, the apparent Km of the system being only minimally affected. It is concluded that the activity of amino acid transport system L in the JAR human placental choriocarcinoma cell line is stimulated by C-kinase, inhibited by CaM-kinase and unaffected by A-kinase.


Profiles of sex steroids, fecundity and spawning of a migratory characiform fish from the Paraguay-Paraná basin: a comparative study in a three-river system.
This study investigated for the first time the reproductive biology of Prochilodus lineatus in a system of rivers in southeastern Brasil, relating it to the role of tributary rivers in the reproductive success of this important commercial fish in the Upper Paraná River basin, where a cascade of hydroelectric dams were deployed. Specimens were caught bimonthly in three river sites: (S1) Grande River, downstream from the Porto Colômbia dam; (S2) Pardo River; and (S3) Mogi Guaçu River. Sex steroid plasma levels, fecundity, follicular atresia, oocyte diameter and gonadosomatic index (GSI) were compared among sites. In S1, fish exhibited changes in the reproductive parameters: lower GSI, oocyte diameter and fecundity and higher follicular atresia index, when compared to S2 and S3. Frequency of maturing fish was higher in S3 and spawning was only registered in S3. In sites S2 and S3, plasma concentrations of testosterone and 17β-estradiol in females and testosterone in males showed wide variations following gonadal maturation. Fish from S1 showed few significant variations in sex steroid concentrations throughout the gonadal cycle. These results indicate that P. lineatus does not reproduce in Grande River (S1), but probably uses the Pardo River (S2) as a migratory route towards the Mogi Guaçu River (S3) where they complete gonadal maturation and spawning. Our findings contribute for understanding the reproductive biology of P. lineatus and to highlight the importance of tributaries in impounded rivers as a favourable environment for migration and spawning of fish.


Depth-marking the proximal negative response in the pigeon retina.
The depth distribution of proximal negativity in the pigeon retina was investigated with a dye-marking technique. Proximal negativity is recorded in three stages as the retina is penetrated. At and near the surface (level 1) the response is small and phasic: next, during "level 2" the one response exceeds the off response in amplitude: then, at "level 3" the off response exceeds the on response in amplitude. The dye marks were located in thin light microscope sections; they were about 20 micrometer in diameter, and were associated with larger areas of tissue damage. Level 3 dye marks were centred at the middle of the inner plexiform layer, and level 2 dye-marks were distributed more proximally. The amplitude maxima of the PNR are close to the middle of the inner plexiform layer, and are separated by approximately 15 micrometer.


Investigation of the bifurcation level of the common carotid artery and variations of the branches of the external carotid artery in human fetuses.
Variations in the position of the bifurcation of the common carotid artery (CCA) and the origin or branching pattern of the external carotid artery (ECA) are well known and documented. In this study, the bifurcation levels of the CCA and origin variations of the branches of the ECA have been extensively investigated in human fetuses. Bilaterally, 40 carotid bifurcations and 40 ECA and their branches have been examined. A latex solution, which had been diluted with water at a ratio of 25% and colored with red India ink, was injected into the aortic arch. Fetuses were kept at room temperature for 24 h before the ECA and its branches were dissected under the microsurgery microscope. Cases of variation were determined and photographed. The bifurcation level of the CCA was determined to be 55% at the C3 level, 35% at the C4 level, 10% at the C5 level on the right side and 60% at the C3 level, 40% at the C4 level on left side. The distribution of the ECA trunks was determined as follows: A linguofacial trunk was present in 20% of the cases, a thyrolingual trunk in 2.5%, a thyrolinguofacial trunk in 2.5% and an occipitoauricular trunk in 12.5%. Beyond this the ascending pharyngeal artery (APA) was observed in one fetus to originate from the internal carotid artery (ICA). Knowledge of variations in the origin and course of the ECA and its branches is of great importance in surgery and radiological examinations.


Comparative study of tributyltin toxicity on two bacteria of the genus Bacillus.
Tributyltin is a potent biocide mainly used in marine anti-fouling paints. Owing to its widespread distribution in coast areas and its high toxicity to aquatic organisms, the use of this compound is generally restricted and under government regulation. Despite of that, it persists in the aquatic environment. Organotins used in industry have also been detected in terrestrial environments. The persistence and high lipophilicity explain bioaccumulation. The role of bacteria in recycling organic matter prompted us to study the interaction of tributyltin with two ubiquitous bacilli, B. stearothermophilus and B. subtilis, proposed as biological indicators of pollutants with ecological impact. These bacteria have been used as suitable models for the study of toxicity mechanisms of unselective lipophilic compounds (e.g., DDT and endosulfan). Drug effects on growth parameters, oxygen consumption and membrane organization were assessed. Bacteria growth in a liquid complex medium was disturbed by concentrations of TBT as low as 25 nM (8 microgL(-1)), close to the concentration in polluted environments. The respiratory activity is affected by TBT in both microorganisms. Membrane organization, assessed by fluorescence polarization of two fluidity probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and a propionic acid derivative (DPH-PA), was also perturbed by the xenobiotic. Alterations on growth, oxygen consumption and physical properties of membrane lipids are stronger in B. stearothermophilus as compared to B. subtilis. A putative relationship between growth inhibition and respiratory activity impairment induced by TBT and its effects on the physical behaviour of bacterial membrane lipids is suggested.


Cellular uptake studies of two hexanuclear, carboxylate bridged, zinc ring structures using fluorescence microscopy.
Two hexanuclear zinc complexes have been structurally characterized, and evaluation against several cells showed selective toxicity. Cellular uptake revealed a non-specific process, resulting in accumulation within the cell cytoplasm.


Short operation time: an important element to reduce operative invasiveness in pediatric cardiac surgery.
The mini skin incision procedure is considered an important element of minimally invasive cardiac surgery because of its definitive cosmetic advantage. However, the operative hazard of limited exposure may be associated with prolonged operation time and increased surgical insult. A total of 357 consecutive patients undergoing repair of an isolated atrial or ventricular septal defect, in whom the mini skin procedure was applied, were investigated. Patients were grouped by diagnosis and body weight. Univariate and multivariate risk analyses were conducted in the specific patient group undergoing ventricular septal defect repair weighing less than 5 kg. The operation time was reduced by 21.0% (93.4 to 73.8 minutes) during this time period. Univariate risk analysis revealed that the operation time had a significant correlation with time to extubation (p < 0.0001), catecholamine duration (p = 0.0003), intensive care unit stay (p < 0.0001), hospital stay (p = 0.016), arterio-alveolar oxygen tension difference at the time of extubation (p = 0.0253), and furosemide dose required in the first 24 hours (p = 0.0332). Multiple linear regression analysis revealed that the operation time had an impact on time to extubation, arterio-alveolar oxygen tension difference at the time of extubation, and intensive care unit stay. The length of skin incision was not correlated with any outcome measure. The mini skin incision, if associated with prolonged operation time, may increase the overall insult in pediatric cardiac surgery. In order to reduce operative invasiveness, simultaneous effort to reduce, or at least not to increase, the operation time are mandatory.


Novelties in Brugada Syndrome: Complex Genetics, Risk Stratification, and Catheter Ablation.
Brugada syndrome (BrS) is an inherited arrhythmia syndrome with distinctive electrocardiographic abnormalities in the right precordial leads and predisposes to ventricular arrhythmias and sudden cardiac death in otherwise healthy patients. Its complex genetic architecture and pathophysiological mechanism are not yet completely understood, and risk stratification remains challenging, particularly in patients at intermediate risk of arrhythmic events. Further understanding of its complex genetic architecture may help improving future risk stratification, and advances in management may contribute to alternatives to implantable cardioverter-defibrillators. Here, the authors review the latest insights and developments in BrS.


Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low-grade glioma.
There is a crucial need for pharmacokinetic (PK) data on oral vinorelbine (VNR) in the paediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). A multicentre, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumours, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t1/2 ) and their between-subject variability (CV%) at 60 mg m-2 dose level, were 472 L h-1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (P = .004). Lower area under the concentration-time curve (AUC) levels were observed among children in comparison to adults. Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among paediatric patients.