Role of alkoxyl radicals on the fluorescein-based ORAC (Oxygen Radical Absorbance Capacity) assay.
During the last decades the ORAC (Oxygen Radical Absorbance Capacity) assay has been widely employed to evaluate the in vitro antioxidant capacity of polyphenol-rich fruits, vegetables and beverages. The method employs fluorescein (FLH) as target molecule and AAPH (2,2'-azo-bis(2-amidinopropane)dihydrochloride) as the source of peroxyl radicals (ROO•). The protection of FLH, afforded by antioxidants (XH), is often characterized by kinetic profiles with clear lag times (LT), which are directly associated with the stoichiometry (n) of the XH-ROO• reaction. However, even for simple phenolic compounds, the LT measured imply large n values (defined as the number of ROO• moles trapped by each antioxidant molecule) which cannot be explained by a simple reaction mechanism. Nonetheless, they can be explained when considering the formation of alkoxyl radicals (RO•) from the recombination of two AAPH-derived ROO•. In the present work, we provide kinetic data showing that, in the zero order kinetic limit of FLH consumption, there is a low reaction rate incompatible with total trapping of ROO•. Thus, the consumption of FLH should be mostly related to its reaction with RO•. In addition, we present data regarding the assumption that in competitive measurements, the LT is due to efficient trapping of the ROO• by the added phenols, leading to high n values (1.7 to 23) for mono and polyphenols. These values are not in agreement with kinetic studies of the antioxidant consumption mediated by the presence of AAPH carried out by HPLC-DAD technique, which imply a competition by RO•. The results suggest that the use of FLH as probe at low concentrations give, for several antioxidants, ORAC values mainly related to their reaction towards RO• radicals instead of primary ROO•radicals.


Computational Analysis of Antibody Paratopes for Antibody Sequences in Antibody Libraries.
To ensure the functionalities of the antibodies in phage-displayed synthetic antibody libraries, we use computational method to evaluate the designs of the antibody libraries. The computational methodologies developed in our lab for designing antibody library provide rich information on the function of the designed antibody sequences-adequate antibody designs for a specific antigen type should have predicted paratopes for the antigen type. This computational assessment of the designed antibody sequences helps eliminate non-functional designs before proceeding to construct the library designs in the wet lab. As such, only reasonable antibody designs are constructed for antibody discoveries.


Vitamin and mineral supplementation for β-thalassemia during COVID-19 pandemic.
Low levels of immune-related micronutrients have been identified in β-thalassemia samples. Moreover, the excess amount of iron, contributing to oxidative stress in the pathogenesis of the disease, alters the immune system in β-thalassemia, which is important during the COVID-19 pandemic. Searches of PUBMED and EMBASE were conducted to identify the level and supplementation of micronutrients in β-thalassemia, published from 2001-May 2020. The review found six observational and five interventional studies supporting the importance of supplementing vitamins and minerals among patients with β-thalassemia. Supplementation of immune-related vitamins and minerals might bring benefits to the immune system, especially in reducing oxidative stress in β-thalassemia.


OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control.
Providing the optimal dosing strategy of a drug for an individual patient is an important task in pharmaceutical sciences and daily clinical application. We developed and validated an optimal dosing algorithm (OptiDose) that computes the optimal individualized dosing regimen for pharmacokinetic-pharmacodynamic models in substantially different scenarios with various routes of administration by solving an optimal control problem. The aim is to compute a control that brings the underlying system as closely as possible to a desired reference function by minimizing a cost functional. In pharmacokinetic-pharmacodynamic modeling, the controls are the administered doses and the reference function can be the disease progression. Drug administration at certain time points provides a finite number of discrete controls, the drug doses, determining the drug concentration and its effect on the disease progression. Consequently, rewriting the cost functional gives a finite-dimensional optimal control problem depending only on the doses. Adjoint techniques allow to compute the gradient of the cost functional efficiently. This admits to solve the optimal control problem with robust algorithms such as quasi-Newton methods from finite-dimensional optimization. OptiDose is applied to three relevant but substantially different pharmacokinetic-pharmacodynamic examples.


Transient behavior of a chemotaxis system modelling certain types of tissue inflammation.
A spatially-distributed mathematical model for the inflammatory response to bacterial invasion of tissue is proposed which includes leukocyte motility and chemotaxis behavior and chemical mediator properties explicitly. This system involves three coupled nonlinear partial differential equations and so is not amenable to analysis. Using scaling arguments and singular perturbation techniques, an approximating system of two coupled nonlinear ordinary differential equations is developed. This system now permits analysis by phase plane methods. Using the approximating model, the dependence of the dynamic behavior of the inflammatory response upon key process parameters, including leukocyte chemotaxis, is studied.


Individuals, Boundaries, and Graft-versus-Host Disease.
Hematopoietic cell transplantation generates new individuals, transplant chimeras, composed of 2 genetic partners-the patient and donor-derived cells-no longer restricted by their original genomes. Interactions of donor-derived and recipient cells occur prominently at the boundary of the recipient with a third partner, the microbiome, in particular skin and intestinal tract, leading to disruption of microbiome homeostasis. These interactions of donor and patient cells at the boundary set the stage for the development of graft-versus-host disease, an expression of the defense of individuality by recipient and donor. Establishment of tolerance and return of homeostasis at the boundary will allow for the survival of the new integrated, physiologic individual.


Gender, side to side and BMI differences in long thoracic nerve conduction velocity: A novel technique.
The purpose of this study was to describe a new technique to record long thoracic nerve conduction velocity through the axilla as well as to assist in establishing normative values for latency and amplitude of the long thoracic nerve and to evaluate side to side, gender and BMI differences. 26 healthy subjects (12 males/14 females) participated in the study with data collected bilaterally resulting in 52 limbs studied. Surface recording was over the serratus anterior muscle with the recording electrode located on the rib closest to a distance within a standardized range of 22-24 cm distal to the acromion. Stimulation was delivered at the mid axillary line, then again in the supraclavicular region. A caliper was used to measure the distance between the two stimulation sites in order to calculate the nerve conduction velocity. The normal value (mean + 2 SD) for distal latency is <2.7 msec, while the normal value for velocity (mean - 2 SD) is >61.0 m/s. Absolute amplitude values were not calculated. Side to side difference normal values for distal latency, amplitude and velocity are 0.7 msec, 70.3% and 8.5% respectively. A two way analysis of variance (ANOVA) revealed a significant gender and BMI difference in both distal (0.02) and proximal amplitude (0.05) means. There was no significant interaction between gender and BMI for latency or velocity values for either stimulation site. The distal latency values are not significantly different from those reported previously, however long thoracic nerve conduction velocity has not been described before and would be an appropriate way to monitor velocity through the proximal portions of the brachial plexus. Men who qualified as overweight with a BMI greater than 25 demonstrated a larger amplitude when compared with average weight men and women. In contrast women with BMI greater than 25 demonstrated a much smaller amplitude when compared with overweight men and average weight men and women. Absolute amplitude normal values are not reported as BMI may impact the ability to record an accurate amplitude for both men and women. Long thoracic nerve conduction velocity and latency appear to be more reliable measures.


An atypical case of myopic strabismus fixus.
We present an atypical case of progressive fixed hypertropia in a patient with extreme myopia. Myopic strabismus fixus is typically characterized by progressive esotropia and hypotropia, which is caused by the protrusion of the posterior eyeball from the superotemporal quadrant of the extraocular muscle cone. In this case, the patient's right eye was fixed in a superomedial position, and the left eye was fixed and deviated upward. Magnetic resonance imaging revealed protrusion of a posterior scleral staphyloma inferotemporally in each eye. This case illustrates how the pattern of strabismus fixus caused by high myopia depends on the direction of the protrusion of the posterior pole and the resulting displacement of extraocular muscle paths.


A long-standing incomprehensible matter of obstetrics: meconium-stained amniotic fluid, a new approach to reason.
We sought to determine whether meconium-stained amniotic fluid is based on chronic hypoxia or not? In case of chronic hypoxia, higher red blood cell (Rbc) count and/or total hemoglobin levels (Hgb) and/or higher fetal hemoglobin (HbF) and/or lower adult hemoglobin (HbA) levels were expected when compared with controls. Case-control study. Obstetric unit of a tertiary ministry of health hospital. Fifty singleton pregnancies with meconium-stained amniotic fluid and 50 singleton pregnancies with clear amniotic fluid at all stages of labor. Umbilical cord blood samples were collected for determination of total blood parameters and hemoglobin electrophoresis. Red blood cell count, total hemoglobin, fetal and adult hemoglobin contents (HbF and HbA). Red blood cell count, total hemoglobin, fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents were not different between meconium stained and clear amniotic fluid groups. These results suggest that meconium passage may not be associated with chronic fetal hypoxia as demonstrated by similar red blood cell count, total hemoglobin values and fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents.


Development of a multilocus variable number of tandem repeat typing method for Oenococcus oeni.
Oenococcus oeni is responsible for the malolactic fermentation of wine. Genomic diversity has already been established in this species. In addition, winemakers usually report varying starter culture efficiency. The monitoring of indigenous and selected strains is essential for understanding strain survival and implantation during the winemaking process. In this study, we report the development of the first typing scheme for O. oeni using multiple-locus variable number of tandem repeat analysis (VNTR). The discriminatory power of 14 out of 44 tandem repeat loci in the genome of the PSU-1 strain was initially evaluated with a test collection of 18 genotypically distinct starter strains. Then five VNTR loci, which can be easily scored with the technology used here, were identified and used to genotype a collection of 236 strains, previously classified by restriction endonuclease analysis-pulsed-field gel electrophoresis (REA-PFGE) and multilocus sequence typing (MLST) into 136 REA-PFGE types or 110 MLST types. The discriminatory power of VNTR (as determined by Simpson's index of discrimination) was higher than that of the other two methods, with 201 VNTR types. The targeted VNTR markers were found to be stable and did not change for the clones of the same strain deposited in a collection at intervals of several years. Strains isolated from the different wine producing areas or the products were assigned to phylogenetic groups and were statistically linked with the VNTR profiles. Another interesting observation was that the loci were found in sequences homologous to regions encoding for membrane-anchored proteins.


Endoscopic surgery for malignant sinonasal tumours: an eighteen year experience.
Curative resection of malignant tumours of the skull base is increasingly undertaken endoscopically. Hitherto the diverse histology, rarity and long natural history have made it difficult to accrue statistically robust cohorts for comparison with conventional craniofacial resection. It is now possible to make such a comparison in a large personal cohort. Data on all cases of sinonasal malignancy undergoing endoscopic resection with curative intent over an eighteen year period were collected prospectively and analysed for survival and prognostic factors. There were 140 cases, 68 men and 72 women, aged 20-92 years (mean 63 yrs). Follow-up ranged from 6-184 months (mean 60 months). Eighteen different histopathologies were represented with olfactory neuroblastoma (36), malignant melanoma (33) and adenocarcinoma (19) being the commonest. Additional radiotherapy was given in 95 cases and chemotherapy in 49. Overall survival is 84% at 5 years and 69% at 10 years. Overall disease-free survival was 77% at 5 years and 56% at ten. Overall and disease-free survival at 5 (and 10) years is, respectively, 97% and 90% for olfactory neuroblastoma, 79% and 68% for adenocarcinoma and 56% and 39% for malignant melanoma. These results show that endoscopic resection is an alternative to conventional craniofacial resection in selected cases.


Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin.
Aberrant sialylation is accepted as a carcinogenic biomarker. In previous work, fluorescently labeled wheat germ agglutinin (WGA) distinguished between cancerous and normal oral biopsies. The purpose of this study was to investigate WGA-fluorescein isothiocyanate (FITC) as a point-of-care tool for detecting oral malignant and dysplastic lesions in vivo. Subject recruitment was divided into two groups: (1) the clinically normal oral mucosa group; or (2) the presence of clinically suspicious oral lesion(s) group. A WGA-FITC solution was topically applied to observable lesions or to half the subject's mouth (sagittal plane) if lesions were absent. Fluorescent molecular imaging was used to evaluate WGA-FITC localization. Fluorescent imaging in 55 subjects demonstrated that WGA-FITC could detect histopathologically-confirmed cancerous and dysplastic lesions with high sensitivity (100% and 81%, respectively) and specificity (82%). This study supports in vivo fluorescent molecular imaging of WGA-FITC to visualize aberrant sialic acid expression associated with carcinogenesis. This technique resulted in the immediate chairside detection of oral cancerous and dysplastic lesions.


Inducing the production of the bacteriocin paenibacillin by Paenibacillus polymyxa through application of environmental stresses with relevance to milk bio-preservation.
Food processors are keenly interested in natural alternatives to currently used chemical preservatives. Although bacteriocins of beneficial bacteria are one of the promising alternatives, low productivity of bacteriocin producers has been limiting the application of these agents in food processing. The present study was designed to examine the possibility of inducing the production of paenibacillin, a bacteriocin produced by Paenibacillus polymyxa OSY-DF, by exposing this organism to environmental stresses. Cold stress (15 °C for 105 min) caused 2- to 4-fold increase in the antibacterial and specific antibacterial activities of bioreaction's cell-free filtrate against Listeria innocua and Bacillus subtilis. Paenibacillin production increased when the organism was exposed during incubation to pH 6.0. Presence of 1% NaCl in the growth medium, application of oxidative stress by exposure to 3 ppm H2O2, and adjusting aeration to a relatively low rate were also found to induce the expression of paenibacillin but to a limited degree, when compared to the effect of cold stress. Exposure to pH 6 increased the transcription of the paenibacillin structural gene, paeA, whereas no significant change was noticed for the same gene under cold stress. Paenibacillin, produced in sufficient amounts under cold stress, was tested as a potential preservative to control the sporeforming bacterium, B. subtilis, in milk. The initial population of B. subtilis of ~7 log10 CFU/ml decreased to an undetectable level (≤ 1 log10 CFU/ml) within 24 h of incubation of treated milk held at 37 °C. Similarly, paenibacillin was active against L. innocua in milk; the treatment caused 5-log decrease in the organism's population after 7 days of incubation. Taken together, these results demonstrated increased expression of paenibacillin by exposure to selected environmental stresses, particularly cold stress, and that paenibacillin seems promising in the biopreservation of milk and potentially milk products.


Photophysical properties of a rhodium tetraphenylporphyrin-tin corrole dyad. The first example of a through metal-metal bond energy transfer.
The luminescence spectroscopy study and the determination of the photophysical parameters for the M-M'-bonded rhodium meso-tetraphenylporphyrin-tin(2,3,7,13,17,18-hexamethyl-8,12-diethylcorrole) complex, (TPP)Rh-Sn(Me6Et2Cor) 1, was investigated. The emission bands as well as the lifetimes (tau(e)) and the quantum yields (Phi(e); at 77 K using 2MeTHF as solvent) were compared with those of (TPP)RhI 2 (TPP = tetraphenylporphyrin) and (Me6Et2Cor)SnCl 3 (Me6Et2Cor = 2,3,7,13,17,18-hexamethyl-8,12-diethylcorrole) which are the two chemical precursors of 1. The energy diagram has been established from the absorption, fluorescence and phosphorescence spectra. The Rh(TPP) and Sn(Me6Et2Cor) chromophores are the energy donor (D) and acceptor (A), respectively. The total absence of fluorescence in 1 (while fluorescence is observed in the tin derivative 3) indicates efficient excited state deactivation, presumably due to heavy atom effect and intramolecular energy transfer (ET). The large decreases in tau(P) and Phi(P) of the Rh(TPP) chromophore going from 2 to 1 indicate a significant intramolecular ET in the triplet states of 1 with an estimated rate ranging between 10(6) and 10(8) s(-1). Based on the comparison of transfer rates with other related dyads that exhibit similar D-A separations and no M-M' bond, and for which slower through space ET processes (10(2)-10(3) s(-1)) operate, a through M-M' bond ET has been unambiguously assigned to 1.


Blood clot stability and bone formation following maxillary sinus membrane elevation and space maintenance by means of immediate implant placement in humans. A computed tomography study.
The present controlled clinical pilot study proposed to assess blood clot contraction and bone neo-formation following maxillary sinus lift (MSL) with immediate implant placement without using grafts using cone beam tomography exams. Ten implants were placed in ten patients with a residual bone crest height ≥4 and ≤ 7 mm, in maxillary premolars or 1st or 2nd molars regions, using MSL and immediate implant placement without grafts, by means of the lateral window approach. A resorbable membrane (Bio-Gide®, Geistlich, USA) was used to close the window. Computed tomography images were taken after 15 (T1) and 180 (T2) days to assess the rate of blood clot contraction and bone neo-formation. The images were analysed by OsirixMD software. The Shapiro Wilk test was used to verify the normality hypothesis and the data were submitted to Student's paired t-test. The mean of bone clot height in mesial, apical and distal area referred to implant, presented 4.77 mm, 0.77 mm and 5.30 mm respectively. The mean measurements of new bone formation presented 2.95 mm, 0.44 mm and 3.45 mm. The height contraction (coagulum/new bone formation), between T1 and T2, presented 38%, 43% and 35% respectively, with a significant statistical value p < 0.05. The volume measurements at T1 presented a mean volume of 0.90 cm3 sd ± 0.60 cm3 and at T2 a mean volume of 0.75 cm3 sd ± 0.62 cm3, with a significant volume contraction between T1 and T2, p < 0.005. The mean blood clot contraction was 16.52% ± 8.60%. The present study demonstrates consistent bone formation around all assessed implants, although with significant contraction of the blood clot. The need for longitudinal studies to establish a long-term prognosis in different modalities of prosthetic rehabilitation of those implants is strongly suggested.


Adjuvant chemotherapy for the perineural invasion of colorectal cancer.
To evaluate the association of perineural invasion (PNI) with outcomes in patients after colorectal resection of colorectal cancer (CRC) and to assess the effect of PNI on the response to adjuvant chemotherapy. Data were retrospectively reviewed for 178 patients with consecutive stages I-III CRC who underwent curative surgery between January 1999 and December 2004. PNI data were examined, and the overall survival (OS) and disease-free survival rates were analyzed. PNI was detected in 36 of 178 patients (20%) and positively correlated with lymphatic invasion (P = 0.020), venous invasion (P = 0.037), and the incidence of metastasis or recurrence (P = 0.029). Five-year disease-free survival was 46% and 68% (P < 0.001) and the 5-y OS was 64% and 80% (P < 0.001) for patients with and without PNI, respectively. In stage III CRC, multiple regression analysis identified PNI as a strong negative prognostic factor of OS; among PNI-positive patients, median OS with adjuvant chemotherapy was almost twofold higher than that without adjuvant chemotherapy (6 versus 2.8 y; P = 0.017). PNI was a poor predictor of survival among patients with stage III CRC, and adjuvant chemotherapy may attenuate the adverse effects of PNI on survival.


Recurrent voluntary anterior dislocation of the hip: case report and review of the literature.
Recurrent dislocation of the hip is uncommon in children, and anterior dislocation, as in the case reported, is extremely rare. Terminology is often confusing, with "recurrent," "voluntary," and "habitual" dislocations described. The causative pathology of the dislocation must be determined before appropriate treatment can be selected; computed tomography can be helpful in making this decision.


Vestibular nerve and nuclei unit responses and eye movement responses to repetitive galvanic stimulation of the labyrinth in the rat.
Two-second cathodal current pulses were applied at one-minute intervals at a point external to the round window in the ear of each albino rat subject. Responses were recorded in the vestibular nerve ganglion, the vestibular nuclei (single units), or in the eye movements (search coil recording method) of anaesthetized, decerebrated, or alert rats. The unit responses to the galvanic stimuli were characterized and compared with responses to galvanic and rotational stimuli reported in the literature. The main focus of the study, however, was effects of stimulus repetition. In both the vestibular nerve and vestibular nuclei recordings, the responses of many units were substantially larger or smaller at the end of a 13-pulse stimulus train than at the beginning. In the vestibular nuclei, but not in the nerve, there was a slight bias towards a decrease in response magnitude, with 10/88 units showing decreases great enough to be considered as reflecting an habituation process. In contrast, the eye movement responses showed more consistent response decrements, especially in the alert condition, but also in the other conditions (none of the unit recordings were done in alert rats). It is concluded that some of the modifications underlying habituation of the vestibuloocular reflex probably occur in portions of the neuronal reflex pathways that are downstream from the vestibular nuclei.


Non-hierarchical cluster analysis for determination of resistance to worm infection in meat sheep.
The aim of this study was to determine the resistance to worm infection in Santa Inês sheep by combining different sets of gastrointestinal parasite resistance indicator traits, using the k-means algorithm. Records from 221 animals reared in the Mid-North sub-region of Brazil were used. The following phenotypes were used: hematocrit (HCT); white blood cell count; red blood cell count (RBC); hemoglobin (HGB); platelets; mean corpuscular hemoglobin; mean corpuscular volume; mean corpuscular hemoglobin concentration; fecal egg count (FEC); coloration of the ocular mucosa (FAMACHA score); body condition score (BCS); withers height; and rump height. Two files with phenotypic information of animals were edited: complete, including all traits, and reduced, in which only FAMACHA score, HCT, FEC, and BCS were used. For determination of worm resistance, three groups were formed using the k-means non-hierarchical clustering by combining the traits of the complete and reduced analyses. The animals of the group in which individuals had the lowest values for FEC and FAMACHA score, as well as the highest values for HCT, RBC, HGB, and BCS were classified as resistant. In the group with opposite values for the aforementioned traits, the animals were classified as sensitive. The animals of the group with values between the other two groups were classified as moderately resistant. The results obtained in complete and reduced analyses were equivalent. Thus, it is possible to identify animals of the Santa Inês sheep breed according to their status of resistance to worm infection based on a reduced trait set.


[Prevalence and expectations of "alternative and complementary medicine" use during radiotherapy in 2016: A prospective study].
Alternative and complementary medicine is defined as any substance or technique of non-allopathic medicine used to improve health and quality of life. The purpose of this prospective observational study was to evaluate the use of alternative and complementary medicine during radiotherapy. A questionnaire was given the last week of treatment to all patients treated for breast cancer, prostate cancer or head and neck cancer in our centre in 2016. In 2016, 132 patients were included. Fifty-seven patients (43%) used alternative and complementary medicine during radiotherapy, more women (61%) than men (35%) (P=0.005). The use of alternative and complementary medicine varied according to locations: 44% of head and neck cancers, 57% of breast cancers and 24% of prostate cancers, but sex was the confounding factor. If alternative and complementary medicine was used before radiotherapy, 82% of patients used it during treatment, compared to 30% if they were naive (P<10-7). Healing touch (68%), homeopathy (26%) and magnetisers (21%) were the most used alternative and complementary medicines. Sixty-one percent of patients used alternative and complementary medicine to reduce skin and mucosal side effects of treatments, 28% to improve well-being, and 9% to treat cancer. Seventy-two percent of all patients would advise their loved one to use an alternative and complementary medicine and 87% would like information about them in the hospital. Alternative and complementary medicines are used more by women, and by patients who used them before radiotherapy. The desired effects are mainly to reduce the side effects of the treatments. More than 80% of patients, whether or not they use alternative and complementary medicine, demand medical information.


CAN1-SUC2 gene fusion studies in Saccharomyces cerevisiae.
Various gene fusions between the arginine permease and invertase have been constructed in order to obtain information about whether parts of the CAN1 gene product can induce secretion of biologically active invertase missing its own signal sequence. A construction containing 30 N-terminal amino acid residues of the CAN1 gene product fused to invertase was not secreted. When the CAN1 portion was elongated to 477 or 560 amino acid residues, secretion of the fusion proteins was observed. A fusion lacking 59 amino acids at the amino-terminal end of the arginine permease was also secreted. These results indicate that the amino-terminal end of the arginine permease is neither sufficient nor essential for membrane insertion; instead this enzyme should contain an internal targeting sequence facilitating secretion. Some general implications on the biosynthesis and topology of membrane proteins are also discussed as well as the homology with histidine permease.


Pain management in a patient with intractable spinal cord injury pain: a case report and literature review.
Chronic pain is one of the more disturbing sequelae of spinal cord injury, often interfering with the basic activities, effective rehabilitation, and quality of life of the patient. Pain in the cord-injured patient is often recalcitrant to treatment. This dilemma is amplified by the limited availability of effective pharmacological and nonpharmacological treatment options. We identified relevant articles regarding pain after spinal cord injury from the Medline database from 1975 to 2005 using the search terms "spinal cord injury" or "spinal cord injuries" and "pain" or "spasticity or "muscle spasms." We also searched by hand the review articles in a recently published book from the International Association for the Study of Pain Press on spinal cord injury pain, and identified relevant articles through reference lists. We present a patient with intractable spinal cord injury pain who was successfully treated with a pain management plan that addressed the various aspects of spinal cord injury pain. The evidence for treatment options is reviewed.


Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway.
Peripheral axons from auditory spiral ganglion neurons (SGNs) form an elaborate series of radially and spirally oriented projections that interpret complex aspects of the auditory environment. However, the developmental processes that shape these axon tracts are largely unknown. Radial bundles are comprised of dense SGN fascicles that project through otic mesenchyme to form synapses within the cochlea. Here, we show that radial bundle fasciculation and synapse formation are disrupted when Pou3f4 (DFNX2) is deleted from otic mesenchyme. Further, we demonstrate that Pou3f4 binds to and directly regulates expression of Epha4, Epha4⁻/⁻ mice present similar SGN defects, and exogenous EphA4 promotes SGN fasciculation in the absence of Pou3f4. Finally, Efnb2 deletion in SGNs leads to similar fasciculation defects, suggesting that ephrin-B2/EphA4 interactions are critical during this process. These results indicate a model whereby Pou3f4 in the otic mesenchyme establishes an Eph/ephrin-mediated fasciculation signal that promotes inner radial bundle formation.


Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study).
The aim of this study was to estimate the prevalence of the metabolic syndrome in Finnish type 1 diabetic patients and to assess whether it is associated with diabetic nephropathy or poor glycemic control. In all, 2,415 type 1 diabetic patients (51% men, mean age 37 years, duration of diabetes 22 years) participating in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) study were included. Metabolic syndrome was defined according to the National Cholesterol Education Program diagnostic criteria. Patients were classified as having normal albumin excretion rate (AER) (n = 1,261), microalbuminuria (n = 326), macroalbuminuria (n = 383), or end-stage renal disease (ESRD) (n = 164). Glycemic control was classified as good (HbA1c <7.5%), intermediate (7.5-9.0%), or poor (>9.0%). Creatinine clearance was estimated with the Cockcroft-Gault formula. The overall prevalence of metabolic syndrome was 38% in men and 40% in women. The prevalence was 28% in those with normal AER, 44% in microalbuminuric patients, 62% in macroalbuminuric patients, and 68% in patients with ESRD (P < 0.001). Patients with metabolic syndrome had a 3.75-fold odds ratio for diabetic nephropathy (95% CI 2.89-4.85), and all of the separate components of the syndrome were independently associated with diabetic nephropathy. The prevalence of metabolic syndrome was 31% in patients with good glycemic control, 36% in patients with intermediate glycemic control, and 51% in patients with poor glycemic control (P < 0.001). Similarly, metabolic syndrome increased with worsening creatinine clearance. The metabolic syndrome is a frequent finding in type 1 diabetes and increases with advanced diabetic nephropathy and worse glycemic control.


Evaluating survival after allogeneic bone marrow transplant for chronic myeloid leukaemia in chronic phase: a comparison of transplant versus no-transplant in a cohort of 258 patients first seen in Italy between 1984 and 1986. Italian Cooperative Study Group on Chronic Myeloid Leukaemia.
Information on the outcome of allogeneic bone marrow transplant (BMT) for chronic myeloid leukaemia (CML) was previously provided by BMT centres or registries. This report uses the data from another source, based on a cohort of 258 patients aged 50 or less who were first seen and recruited between 1984 and 1986 at 55 Italian hospitals. These patients were registered and followed for a prospective study of the course and prognosis of CML, without any obligations for treatment. All patients had Ph+ CML; 50 of them were transplanted in first chronic phase (CP), and 208 were not transplanted. Leukaemia-free survival at 8 years was 34% (95% CI 20-47%) for the transplant group versus zero in the non-transplant group. Overall survival at 8 years was 43% (95% CI 29-57%) for the transplant group versus 25% (95% CI 19-32%) in the non-transplant group (P = 0.24). The difference in overall survival between transplant and non-transplant was significant in patients less than 30 years old (P = 0.035), but not in patients aged 30-50 years (P = 0.439). This report points out that although freedom from leukaemia could be obtained only with BMT, a beneficial effect of BMT on overall survival could be detected only in a patients' subset, and that many hundreds of cases and a decade could be necessary to evaluate the effect on survival of new transplant policies.


Clinical and patient-reported outcomes of Chinese patients undergoing haemodialysis in hospital or in the community: A 1-year longitudinal study.
Little is known about the effect of haemodialysis (HD) setting on outcomes of patients with end stage renal disease (ESRD). The study aimed at comparing clinical outcomes and patient-reported outcomes (PRO) of patients on community-based (CBHD) and hospital-based haemodialysis (HBHD). A prospective cohort of Chinese ESRD patients receiving HBHD (n = 89) or CBHD (n = 117) in Hong Kong were followed up for 12 months. Subjects were assessed on clinical outcomes of dialysis adequacy (Kt/V) and blood haemoglobin and PRO of health-related quality of life (SF-12v2), general health condition (Global Rating Scale (GRS)) and confidence to cope with their illness (Patient Enablement Instrument (PEI)). Differences between groups were analyzed by independent t-tests for the SF-12v2, GRS and PEI scores. χ(2) tests were used to analyze the difference in proportion of patients reaching the targets of Kt/V and blood haemoglobin and with GRS > 0 and PEI > 0. Multiple linear and logistic regressions were performed to assess the adjusted difference-in-difference estimation. The mean PEI and GRS scores of CBHD patients at 12 months were significantly higher than those of HBHD patients. CBHD patients had significantly greater improvement in self-efficacy and were more likely to be enabled after 12 months than the HBHD patients. The study showed similar clinical outcomes and PRO between CBHD and HBHD but CBHD was more effective than HBHD in promoting patient enablement over a 12-month period. The results suggest added value for patients receiving CBHD and support the transfer of HD care from the hospital to the community.


Parenteral absorption of insulin from the lung in diabetic children.
Semi-synthetic human insulin was delivered via a novel nebulizer to the respiratory tracts of six diabetic children. Blood glucose control obtained was at least as good as a control day when they received their usual dose of subcutaneous insulin.


Analysis of spontaneous sister-chromatid exchanges in vivo by three-way differentiation.
By applying an adaptation of the method of three-way differentiation to murine bone marrow cells in vivo, the basal frequency of sister-chromatid exchange (SCE) per cell was evaluated. An SCE frequency directly proportional to the estimated relative incorporation of 5-bromodeoxyuridine (BrdU) to the chromosomes was observed for the 3 consecutive cell cycles, implying that the majority, if not all, of the SCEs in vivo were produced by the incorporated BrdU. This conclusion was supported by the finding that in the first cycle of division, a very high frequency of cells without SCE was observed. From these data, a spontaneous frequency of SCE as low as 0.15 SCE/cell/cell cycle was inferred.


Cerebral vasculitis and multi-focal neurological deficits due to allopurinol-induced hypersensitivity syndrome.
Drug-induced hypersensitivity syndrome (DIHS) is a multi-system syndrome resulting from an idiosyncratic reaction to medication. While it commonly results in multi-organ involvement, particularly the liver, there are few reports of DIHS causing cerebral vasculitis and neurological deficits. We report the case of a 63-year old woman with DIHS secondary to allopurinol leading to multiple neurological deficits with magnetic resonance imaging findings consistent with a cerebral vasculitis.


The female paraplegic in Spain: preliminary report.
A survey has been made of 70 out of the 166 female paraplegic and tetraplegic patients treated at the Spinal Unit of La Fe Hospital of Valencia in order to record the aetiology, main medical problems, domestic resettlement, functional, social and industrial rehabilitation of the patients. The results are discussed.


Solution structure of the DNA complex with a quinacrine-netropsin hybrid molecule by NMR spectroscopy.
The solution structures of 1:1 complexes of a quinacrine-netropsin hybrid molecule with the self-complementary DNA duplexes, d(CGCGAATTCGCG)2 and d(CGAATTCG)2, have been studied by one- and two-dimensional 1H NMR spectroscopy. The NOE data indicate that the acridine ring of the hybrid intercalates into the 5'-GpA step and its netropsin moiety spans the minor groove of the central AATT region.


Rhabdomyolysis secondary to bee sting.
Insect stings belonging to Hymenoptera defined as wasps, yellow jackets, bees, or hornets by human usually result in unserious clinical pictures that go with pain. Rhabdomyolysis following a bee sting is a rare condition. This paper emphasizes "rhabdomyolysis" as a rare complication of this frequently observed envenomation. Rare but severe clinical results may occur due to multiple bee stings, such as intravascular hemolysis, rhabdomyolysis, acute renal insufficiency, and hepatic dysfunction. In bee stings as in our case, clinicians should be alert for rhabdomyolysis in cases with generalized body and muscle pain. Early onset alkaline diuresis and management in patients with rhabdomyolysis are vital in protecting the renal functions and preventing morbidity and mortality.


Movement quality of conventional prostheses and the DEKA Arm during everyday tasks.
Conventional prosthetic devices fail to restore the function and characteristic movement quality of the upper limb. The DEKA Arm is a new, advanced prosthesis featuring a compound, powered wrist and multiple grip configurations. The purpose of this study was to determine if the DEKA Arm improved the movement quality of upper limb prosthesis users compared to conventional prostheses. Case series. Three people with transradial amputation completed tasks of daily life with their conventional prosthesis and with the DEKA Arm. A total of 10 healthy controls completed the same tasks. The trajectory of the wrist joint center was analyzed to determine how different prostheses affected movement duration, speed, smoothness, and curvature compared to patients' own intact limbs and controls. Movement quality decreased with the DEKA Arm for two participants, and increased for the third. Prosthesis users made slower, less smooth, more curved movements with the prosthetic limb compared to the intact limb and controls, particularly when grasping and manipulating objects. The effects of one month of training with the DEKA Arm on movement quality varied with participants' skill and experience with conventional prostheses. Future studies should examine changes in movement quality after long-term use of advanced prostheses. Clinical relevance Movement quality with the DEKA Arm may depend on the user's previous experience with conventional prostheses. Quantitative analyses are needed to assess the efficacy of novel prosthetic devices and to better understand how to train people to use them effectively.


Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma.
To evaluate the diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) features of cervical spinal cord astrocytoma. Eleven patients with cervical spinal cord astrocytomas and 10 healthy volunteers were recruited in this study. Conventional magnetic resonance imaging (MRI) and axial DTI were performed on a 3.0T MRI system. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values for the lesions were measured. DTT was performed using the principal diffusion direction method. ADC values of the lesions and the normal-appearing tissue around the tumour (NATAT) on T2-weighted imaging (T2WI) increased. The ADC values of the lesions were higher. The FA values of the lesions and the NATAT decreased significantly, with the lesions having lower FA values. The RD value (1.36±0.49) of the tumours was significantly higher than those found in the healthy controls, but similar for the AD value (1.84±0.56). There were no differences in ADC or FA values between lesions and NATAT in McCormick Type I vs. Type II patients. Based on the DTT, 7 patients with solid mass tumours were classified as Type I. One patient with a solid mass, 2 patients with cystic degeneration inside the lesions, and 1 patient with a cyst around the mass were classified as Type II. FA values of the cervical spinal cord astrocytoma decreased, but the ADC values increased. DTI was sensitive for the evaluation of pathological changes that could not be visualized on T2WI. Our preliminary study indicates that DTT can be used to guide operation planning, and that axial images of DTT may be more valuable.


Impact of climate change induced future rainfall variation on dynamics of arid-humid zone transition in the western province of India.
The transition of the Earth's climate from one zone to another is one of the major causes behind biodiversity loss, rural-urban migration, and increasing food crises. The rising rate of arid-humid zone transition due to climate change has been substantially visible in the last few decades. However, the precise quantification of the climate change-induced rainfall variation on the climate zone transition still remained a challenge. To solve the issue, the Representative Grid Location-Multivariate Adaptive Regression Spline (RGL-MARS) downscaling algorithm was coupled with the Koppen climate classification scheme to project future changes in various climate zones for the study area. It was observed that the performance of the model was better for the humid clusters compared to the arid clusters. It was noticed that, by the end of the 21st century, the arid region would increase marginally and the humid region would rise by 24.28-36.09% for the western province of India. In contrast, the area of the semi-arid and semi-humid regions would decline for the study area. It was observed that there would be an extensive conversion of semi-humid to humid zone in the peripheral region of the Arabian sea due to the strengthening of land-sea thermal contrast caused by climate change. Similarly, semi-arid to arid zone conversion would also increase due to the inflow of dry air from the Arabian region. The current research would be helpful for the researchers and policymakers to take appropriate measures to reduce the rate of climate zone transition, thereby developing the socioeconomic status of the rural and urban populations.


Effects of the First 1000 Days Program, a systems-change intervention, on obesity risk factors during pregnancy.
First 1000 Days is a systems-oriented program starting in early pregnancy lasting through the first 24 months of infancy focused on preventing obesity and related risk factors among low income, mother-infant pairs. The program was developed in partnership with stakeholders to create an infrastructure for system-wide change. It includes screening for adverse health behaviors and socio-contextual factors, patient navigation and educational materials to support behavior change and social needs, and individualized health coaching for women at highest risk of obesity and has been shown to reduce excess gestational weight gain for women who were overweight at the start of their pregnancy. The purpose of this study was to examine changes from the first to third trimester for women participating in the First 1000 Days Program. We collected information through self-administered questionnaires during the first and third trimester of gestation and from electronic health records relating to obesity risk factors. Measures collected included behavior (i.e., diet, physical activity and screen time) and psychosocial (i.e., anxiety) outcomes, as well as enrollment in Women, Infant, and Children (WIC) program. We examined the extent to which participation in the program was associated with changes in behaviors and psychosocial outcomes among women during pregnancy. Women completed surveys at their initial and third trimester prenatal visits (n = 264). Mean age (SD) was 30.2 (5.51) years and 75% had an annual household income of <$50,000. Mean pre-pregnancy body mass index (BMI) was 27.7 kg/m2 and 64% started pregnancy with a BMI ≥ 25 kg/m2. In multivariable adjusted models, we observed decreases in intake of sugary-drinks (- 0.95 servings/day; 95% CI: - 1.86, - 0.03) and in screen time (- 0.21 h/day; 95% CI: - 0.40, - 0.01), and an increase in physical activity (0.88 days/week; 95% CI: 0.52, 1.23) from the first to third trimester. We also observed a decrease in pregnancy-related anxiety score (- 1.06 units; 95% CI: - 1.32, - 0.79) and higher odds of enrollment in Women, Infant, and Children (WIC) program (OR: 2.58; 95% CI: 1.96, 3.41). Our findings suggest that a systems-oriented prenatal intervention may be associated with improvements in behaviors and psychosocial outcomes during pregnancy among low-income mothers. ClinicalTrials.gov ( NCT03191591 ; Retrospectively registered on June 19, 2017).


Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing.
We examined the ability of a set of cloned chicken ovalbumin (cOVA)-specific, Id-restricted, T cell hybridomas to produce interleukin-2 in response to cOVA presented by the Ia+ B cell lymphoma line, A20-2J. Although viable A20-2J cells presented native, denatured, and fragmented cOVA more or less equally well, A20-2J cells that were glutaraldehyde-fixed could present only enzymatically or chemically fragmented cOVA. These results suggest that antigen fragmentation may be both necessary and sufficient to define accessory cell processing of soluble antigens so that they may be recognized in association with I-region molecules by T cells.


Dentistry's social contract and dental students' moral inclusiveness.
Under dentistry's social contract with the public, dental professionals have a social responsibility to address the oral health needs of the population at large. However, dental education places little emphasis on such moral commitments. By ascertaining dental students' stance regarding these notions, we may be able to inform changes in dental education. This paper thus explores dental students' comprehension of dentistry's social contract using the concepts of moral inclusion, moral community and empathy. A cross-sectional online survey collected information from undergraduate dental students at the Faculty of Dentistry, University of Toronto (N = 430). Moral inclusion was assessed through the breadth of students' moral community by computing a "moral inclusion score" (MIS) from Likert scale responses to statements that asked students about their duty of care for different population groups, wherein a higher MIS indicated a broader moral community and in turn greater moral inclusiveness. Empathy was assessed using Likert scale responses to statements that gauged the extent to which students understood the effect of social determinants on people's health. Association of the MIS with environmental, institutional and student-related factors was also investigated using non-parametric tests and linear regression. The survey yielded a response rate of 51.4% (n = 221). Overall, students in this sample were morally inclusive and displayed empathy. Regression results showed that the MIS was most strongly associated with choosing a small town/rural area as a future practice location (β = 4.76, 95% CI: 0.52, 9.01) and viewing patients as consumers (β = -3.71, 95%CI: -7.13, -0.29). Students in this sample made morally inclusive choices, which implied that they had a basic understanding of the obligations under dentistry's social contract. Improving knowledge and experience with regards to addressing the social and economic determinants of oral health and access to oral health care may positively influence students' perceptions of their professional duties under the social contract.


Patient satisfaction with childbirth after external cephalic version.
To assess acceptance and impact of external cephalic version (ECV) for breech presentation at term on maternal satisfaction with childbirth. Retrospective study on n = 131 women with breech presentation comparing maternal satisfaction after ECV and consecutive childbirth (n = 66; 50.4% of these successful attempts in n = 33; 50%) against the group without ECV and primary caesarean section (CS) (n = 65; 49.6%) instead using a questionnaire. Women with successful ECV tolerated side effects of the intervention better than after unsuccessful ECV (pain, tocolytics, mental and physical state, for all p < 0.001). They were not more satisfied with childbirth than women who experienced an unsuccessful ECV (p = 0.37). However, they would undergo the procedure again (p = 0.003) and would recommend it to other women (p < 0.001). Only women with spontaneous vaginal deliveries after successful version were more satisfied with childbirth than women with planned CS (p = 0.05). Women with version attempts tend to perceive childbirth as being less problematic with fewer complications (9.5 vs. 19%, p = 0.12). Unsuccessful ECVs had no negative impact on satisfaction with childbirth (p = 0.072). Attempting ECV seems to be an option for increasing the rate of vaginal births with breech presentation without negative impact on maternal satisfaction regarding consecutive childbirth.


Persistent pleuritic chest pain in a patient with cystic fibrosis.
Pleural effusion is rare in cystic fibrosis. Infection leading to pleural effusion is likely to be polymicrobial, including contributory fungal infection; microbiology of pleural fluid is commonly discordant with sputum. https://bit.ly/3MJXrhk.


Floral transcriptomes reveal gene networks in pineapple floral growth and fruit development.
Proper flower development is essential for sexual reproductive success and the setting of fruits and seeds. The availability of a high quality genome sequence for pineapple makes it an excellent model for studying fruit and floral organ development. In this study, we sequenced 27 different pineapple floral samples and integrated nine published RNA-seq datasets to generate tissue- and stage-specific transcriptomic profiles. Pairwise comparisons and weighted gene co-expression network analysis successfully identified ovule-, stamen-, petal- and fruit-specific modules as well as hub genes involved in ovule, fruit and petal development. In situ hybridization confirmed the enriched expression of six genes in developing ovules and stamens. Mutant characterization and complementation analysis revealed the important role of the subtilase gene AcSBT1.8 in petal development. This work provides an important genomic resource for functional analysis of pineapple floral organ growth and fruit development and sheds light on molecular networks underlying pineapple reproductive organ growth.


Simple method for determining proper length of artificial chordae in mitral valve repair.
A simple method for determining the length of artificial chordae in mitral reconstructive operations is described. A small tourniquet is used for fine adjustment of the length of polytetrafluoroethylene stitches before tying them during leaking test. We have used this technique in 10 consecutive patients with anterior mitral leaflet prolapse since August 1992. Intraoperative transesophageal echocardiography revealed no or only trace mitral regurgitation after valve repair in all cases. This method minimized the time of determining the proper length of artificial chordae and achieved good results.


Pinealomas and germinomas in children.
A series of 34 pinealomas and intracranial germinomas in childhood (age less than 20), from two tumor registries, is analyzed. Male to female ratio was 2:1. Median age was 12 years. Visual complaints and endocrine disturbances were the most common presenting symptoms. Papilledema, visual field deficits, and oculomotor abnormalities were the principal findings at diagnosis. Cumulative probability of survival (CPS) of the entire series at one year was 0.65, at two years 0.54, and at five years 0.54. Best survival was with treatment by operation and radiation: CPS at one year was 0.82, at two years 0.82, and at five years still 0.82. Survival was similar with pineal region tumors and with suprasellar tumors. Most long-term survivors, particularly with suprasellar germinomas, had permanent hormonal deficits requiring replacement therapy.


Colorectal cancer in patients under 30 years of age. Contributors to the Southwestern Surgical Congress Unusual Case Registry.
The Southwestern Surgical Congress (SWSC) recently initiated a registry of unusual cases. The registry was created to collect information on patients with uncommon conditions treated by members of the Congress. The registry is intended to be a source of clinical information for the members, as well as a tool for the conduct of retrospective and prospective clinical and epidemiologic studies. As the first project, we collected data on patients with colorectal cancer who were 30 years of age or less at the time of diagnosis. Letters were sent to all members of the SWSC soliciting information about such patients. Data collection sheets were subsequently mailed to those who responded to the letter. The data sheets asked for demographic data, as well as pertinent anamnestic, clinical, and staging information. Operative reports, pathology reports, and paraffin-embedded tissue blocks were also requested. Twenty-four members contributed a total of 55 patients to the registry. There were 23 males (age range: 14 to 30 years) and 32 females (age range: 16 to 30 years). In 37 patients, factors assumed to predispose to colorectal cancer were identified. The most common predisposing factor was smoking. There were 12 right colon tumors, 24 left colon tumors, and 11 rectal tumors. According to the TNM classification, 6 patients had stage I disease, 15 patients had stage II disease, 17 patients had stage III disease, and 17 patients had stage IV disease. Tissue blocks from tumor and adjacent bowel will be examined to address the issue of a possible genetic predisposition for cancer at the molecular level, in these young patients. We will also assess the independent influence of age on prognosis by comparing the actuarial survival and recurrence rates in patients from the registry with data from older patients who are matched for the presence of other known prognostic factors. The Unusual Case Registry will provide the members of the Congress with a valuable database of clinical information. Furthermore, this method of compilation will facilitate the collection of relatively large patient samples over a short period of time. This will greatly facilitate the conduct of original and relevant collaborative prospective studies of uncommon diseases within the framework of the SWSC.


Exopolysaccharide production by Streptococcus thermophilus SY: production and preliminary characterization of the polymer.
To evaluate the effect of yeast extract (YE) concentration, temperature and pH on growth and exopolysaccharide (EPS) production in a whey-based medium by Streptococcus thermophilus SY and to characterize the partially purified EPS. Factorial experiments and empirical model building were used to optimize fermentation conditions and the chemical composition, average molecular weight (MW) and rheological properties of aqueous dispersions of the EPS were determined. Exopolysaccharide production was growth associated and was higher (152 mg l(-1)) at pH 6.4 and 36 degrees C with 4 g l(-1) YE. High performance size exclusion chromatography of the partially purified EPS showed two peaks, with a weight average MW of 2 x 10(6) and 5 x 10(4), respectively. The EPS was a heteropolysaccharide, with a glucose : galactose : rhamnose ratio of 2 : 4.5 : 1. Its water dispersions had a pseudoplastic behaviour and showed a higher viscosity of xanthan solutions. The fermentation conditions and some properties of an EPS produced by Strep. thermophilus, a dairy starter organism, were described.


Stent expansion of restrictive Fontan conduits to nominal diameter and beyond.
Mechanical factors may cause bottlenecks in a Fontan circuit. Extracardiac conduits (ECC) are placed at a young age, but the materials do not allow growth. Restriction in ECC dimensions may deteriorate the function of the circuit. This study aimed to evaluate the feasibility and safety of stent expansion of an ECC to the nominal dimension at the time of implant and, if possible, beyond nominal. Retrospective, single-center observational review of all ECC Fontan patients who received a stent to expand a previously placed surgical conduit. A total of 44 restrictive conduits were stented over a 14-year study period with a median of 11.8 (interquartile ranges [IQR]: 9.1-13.8) years after ECC placement. Cross-sectional areas were a median of 30% (IQR: 21-42) smaller than the originally placed ECC; there was no gradient in 23/44 patients and in 21/44, a minimal gradient of 1.3 ± 0.5 (range 1-3 mmHg). All conduits could be enlarged with a significant (p < 0.0001) increase in diameter from 13.6 ± 1.8 to 19.2 ± 1.2 mm, corresponding to a median cross-sectional area increase of 171% (IQR: 153-220). In three patients where the conduits were not contracted, expansion of between 127% and 165% was obtained. There were no conduit ruptures and only one minor complication. ECC in some Fontan patients become smaller than nominal over time, usually without overt symptoms. The dimensions of ECC's can be safely and significantly increased to nominal or even beyond employing stenting. It allows adjustment of ECC dimensions to compensate for somatic growth.


Developmental learning of complex syntactical song in the Bengalese finch: a neural network model.
We developed a neural network model for studying neural mechanisms underlying complex syntactical songs of the Bengalese finch, which result from interactions between sensori-motor nuclei, the nucleus HVC (HVC) and the nucleus interfacialis (NIf). Results of simulations are tested by comparison with the song development of real young birds learning the same songs from their fathers. The model shows that complex syntactical songs can be reproduced from the simple interaction between the deterministic dynamics of a recurrent neural network and random noise. Features of the learning process in the simulations show similar trends to those observed in empirical data on the song development of real birds. These observations suggest that the temporal note sequences of songs take the form of a dynamical process involving recurrent connections in the network of the HVC, as opposed to feedforward activities, the mechanism proposed in the previous model.


Segmentation of African countries based on infection and death rates of COVID-19 before vaccination: A rigid population to source for workforce amidst the pandemic?
This study established segments among African countries to show the hierarchies of COVID-19 infection and death rates across the continent before the commencement of vaccination. Four clusters were extracted, each consisting of countries with a similar number of cumulative infections and deaths per 100 thousand population. When compared with the pre-vaccination figures from Europe, Americas, and Asia, it was observed that the African population exhibited a good level of rigidity and resilience to the pandemic, pre-vaccination. Majority of African countries - evaluating to 84% - were clustered into the segment with low infection and low death rates. Only 4% of the countries were clustered into the higher infection and highest death rates segment. This is an indication of the rigidity of a greater part of the African population to COVID-19 before vaccination. To forestall total business shutdown in the event of a similar pandemic in the future, multinational corporations could explore their workforce from the African population given the level of rigidity exhibited pre-vaccination.


Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.
The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP. This study included 52 infants born at <31 wk gestational age (non-ROP n = 33, nonproliferative ROP n = 10, treated for ROP n = 9). VEGF concentrations were analyzed in blood samples collected at birth, at 3 d postnatal age, and then weekly until at least a gestational age of 35 wk. VEGF concentrations at birth did not differ between groups, independent of later ROP status. In contrast, VEGF serum concentrations were significantly higher at first detection of ROP in infants who were later treated for ROP compared to infants without ROP. At the time of laser therapy, serum VEGF concentrations did not differ between groups. Circulatory concentrations of VEGF, in infants who later developed severe ROP, were elevated at the time when ROP first was detected but not at the time when current treatment most often occurred. This supports the need for further studies of circulating VEGF in relation to the timing of ROP treatment.


Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels.
Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.


Non-Invasive Detection, Precise Localization, and Perioperative Navigation of In Vivo Deep Lesions Using Transmission Raman Spectroscopy.
Non-invasive detection and precise localization of deep lesions have attracted significant attention for both fundamental and clinical studies. Optical modality techniques are promising with high sensitivity and molecular specificity, but are limited by shallow tissue penetration and the failure to accurately determine lesion depth. Here the authors report in vivo ratiometric surface-enhanced transmission Raman spectroscopy (SETRS) for non-invasive localization and perioperative surgery navigation of deep sentinel lymph nodes in live rats. The SETRS system uses ultrabright surface-enhanced Raman spectroscopy (SERS) nanoparticles with a low detection limit of 10 pM and a home-built photosafe transmission Raman spectroscopy setup. The ratiometric SETRS strategy is proposed based on the ratio of multiple Raman spectral peaks for obtaining lesion depth. Via this strategy, the depth of the phantom lesions in ex vivo rat tissues is precisely determined with a mean-absolute-percentage-error of 11.8%, and the accurate localization of a 6-mm-deep rat popliteal lymph node is achieved. The feasibility of ratiometric SETRS allows the successful perioperative navigation of in vivo lymph node biopsy surgery in live rats under clinically safe laser irradiance. This study represents a significant step toward the clinical translation of TRS techniques, providing new insights for the design and implementation of in vivo SERS applications.


Human serum contains a protease that protects against cytotoxic activity of Bacillus anthracis lethal toxin in vitro.
The role of innate immunity in the host response to Bacillus anthracis is poorly understood. We found that normal human serum contains an antitoxin mechanism that is capable of protecting macrophages in vitro from B. anthracis lethal toxin-mediated killing. This protective activity was limited to defined amounts of toxin and was lost by heat treatment or serum dilution. Some person-to-person variation in the protective activity of serum was noted, especially with higher concentrations of lethal toxin. A similar protective activity was found in murine serum, though human serum consistently neutralized more toxin than did murine serum. The protective activities of both murine and human sera correlated with cleavage of the protective antigen into two fragments with approximate molecular sizes of 20 and 50 kDa that were recognized by the monoclonal antibodies 7.5G and 10F4, respectively. This pattern of fragmentation is consistent with cleavage at multiple sites, including the furin-susceptible site. Cleavage was abolished by heat treatment and calcium chelation. These findings highlight a potential role for serum proteases in protection against the lethal toxin of B. anthracis.


Regulatory role of E3 ubiquitin ligases in normal B lymphopoiesis and B-cell malignancies.
E3 ubiquitin ligases play an essential role in protein ubiquitination, which is involved in the regulation of protein degradation, protein-protein interactions and signal transduction. Increasing evidences have shed light on the emerging roles of E3 ubiquitin ligases in B-cell development and related malignances. This comprehensive review summarizes the current understanding of E3 ubiquitin ligases in B-cell development and their contribution to B-cell malignances, which could help explore the molecular mechanism of normal B-cell development and provide potential therapeutic targets of the related diseases.


Gender Performance in the Sporting Lives of Young Trans* People.
This paper explored how UK trans* youth experienced Physical Education (PE) during secondary school, and its impact on remaining physically active. Seven self-identified trans* people aged 14-25 took part in semi-structured interviews. Findings show participants' performances of gender were restricted by practices privileging the "natural" gender binary. Following school, medical procedures or other physical changes were desired in order to "pass" as their chosen gender before physical activity could occur. Recommendations are presented for improvements to PE policy for trans* youth.


Selective isomer emission via funneling of exciton polaritons.
Polaritons in organic systems has shown the potential to modify chemical properties and to mediate long-range energy transfer between individual chromophores, among other capabilities. Here, we demonstrate that strong coupling and formation of organic exciton-polaritons can be used to selectively tune the isomer emission of organic molecules. By taking advantage of their delocalized and hybrid character, polaritons emerging in the strong coupling regime open a new relaxation pathway that allows for an efficient funneling of the excitation between the molecular isomers. We implement this by strong coupling to trans-DCS (E-4-dimethylamino-4′cyanostilbene)molecules, which present two isomers in different amounts when immersed in a polymer matrix. Thanks to this new relaxation pathway, the photoexcitation that is first shared by the common polaritonic mode is then selectively funneled to the excited states of one of the isomers, recognizing pure emission from the isomeric states that do not contribute to emission under normal conditions.


Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II.
Cellular metabolism, particularly glycolysis, is altered during the metastatic process and is highly associated with tumor progression and apoptosis resistance. Oroxylin A, a natural plant flavonoid, exhibits chemopreventive and therapeutic anti-inflammatory and anticancer potential. However, the anticancer effects of oroxylin A on non-small cell lung carcinoma (NSCLC) remain poorly understood. In vitro studies were performed using 2D and 3D conditions. The effects on anoikis-sensitization and glycolysis-inhibition of oroxylin A in human non-small cell lung cancer A549 cells were examined. In vivo murine lung metastasis experiments were utilized to assess the anti-metastatic capacity of oroxylin A. ROS-mediated activation of c-Src following detachment caused anoikis resistance in A549 cells. Oroxylin A sensitized A549 cells to anoikis by inactivating the c-Src/AKT/HK II pathway in addition to inducing the dissociation of HK II from mitochondria. Prior to sensitizing A549 cells to anoikis, oroxylin A decreased the ATP level and inhibited glycolysis. Furthermore, oroxylin A inhibited lung metastasis of A549 cells in vivo in nude mice. Oroxylin A sensitized anoikis, which underlies distinct glucose-deprivation-like mechanisms that involved c-Src and HK II. The findings in this study indicated that oroxylin A could potentially be utilized in the development of improved metastatic cancer treatments.


Advanced glycation end-product-inhibited cell proliferation and protein expression of beta-catenin and cyclin D1 are dependent on glycogen synthase kinase 3beta in LLC-PK1 cells.
Glycogen synthase kinase 3beta (GSK3beta) is increased by high glucose in mesangial cells. Thus, we studied the role of GSK3beta in advanced glycation end-product (AGE)-induced effects in the proximal tubule-like LLC-PK1 cells. We found that AGE (100 microg/ml) time-dependently (8-48 h) increased phospho-GSK3beta-Tyr216 (active GSK3beta) and time-dependently (4-24 h) decreased phospho-GSK3beta-Ser21/9 (inactive GSK3beta) protein expression. Meanwhile, AGE (100 microg/ml) activated GSK3beta kinase at 8-48 h. AGE (100 microg/ml) dose-dependently (75-100 microg/ml) decreased beta-catenin protein expression but AGE did not decrease beta-catenin protein expression until 48 h. SB216763 (a GSK3beta inhibitor) and GSK3beta shRNA attenuated AGE (100 microg/ml)-inhibited cell proliferation and protein expression of beta-catenin and cyclin D1 at 48 h. SB216763 also attenuated AGE-induced type IV collagen. We conclude that AGE activates GSK3beta in LLC-PK1 cells. AGE-inhibited beta-catenin and cyclin D1 protein expression are dependent on GSK3beta. Moreover, AGE-inhibited cell proliferation and AGE-induced type IV collagen protein expression are dependent on GSK3beta.


Production of (+)-globulol needle crystals on the surface mycelium of Quambalaria cyanescens.
The structure of unique colorless needle crystals growing from the surface mycelium of the basidiomycete Quambalaria cyanescens and identified as (+)-globulol was followed by mass spectrometry, X-ray diffraction, and polarimetry. The mechanism of (+)-globulol fragmentation is proposed based on collision induced dissociation mass spectrometry. X-Ray analysis revealed that crystal packing is governed by hydrogen bond O-H.....O connecting the molecules into an infinite helix along a 3-fold screw axis propagating along the longest dimension of the needle crystal (c-axis of the unit cell). The X-ray diffraction data correspond well with the proposed structure determined by mass spectrometry.


Alkylation of succinates: synthesis of Ro 32-3555.
A short synthesis, based on a succinate acylation-alkylation-decarboxylation approach, of the clinical compound Ro 32-3555 is reported. The nature of the selectivity in the mono-alkylation of succinates was examined under varying enolization conditions and in the presence of chaotropic additives.


Interferon and cytokine responses to SARS-coronavirus infection.
The sudden emergence of severe acute respiratory syndrome (SARS) has boosted research on innate immune responses to coronaviruses. It is now well established that the causative agent, a newly identified coronavirus termed SARS-CoV, employs multiple passive and active mechanisms to avoid induction of the antiviral type I interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are strongly upregulated. The imbalance in the IFN response is thought to contribute to the establishment of viremia early in infection, whereas the production of chemokines by infected organs may be responsible for (i) massive immune cell infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of adaptive immunity. Here, we will review the most recent findings on the interaction of SARS-CoV and related Coronaviridae members with the type I interferon and cytokine responses and discuss implications for pathogenesis and therapy.


Bipolar Hemiarthroplasty should not be selected as the primary option for intertrochanteric fractures in elderly patients aged 85 years or more.
This study aimed to compare the early outcome of proximal femoral nail antirotation (PFNA) and bipolar hemiarthroplasty (BPH) in elderly intertrochanteric fractures (ITFs) patients aged 85 years or more.This is a prospective cohort study, and we analyzed 120 elderly patients aged 85 years or more presented with ITFs who underwent BPH and PFNA between January 2017 and July 2018. 84 patients treated with PFNA were set as Group A, and 36 patients treated with BPH were set as Group B. Data such as gender, age, period of follow-up, fracture classification (according to Evans-Jensen classification), preoperative ASA (American Society of Anesthesiologists) physical status, interval between injury and operation, method of anaesthesia, duration of operation time, blood loss during surgery, time of weight bearing after operation, incidence of complications 2 weeks after operation, mortality rates and Harris Hip Score 12 months after operation were recorded and compared.There are no statistically significant differences when compared general data in patients from group A and B (P > .05). Operation time in Group A is less than Group B (103.33, 40-230 min vs 122.64, 75-180 minute, P < .01). Blood loss during surgery in Group A is less than Group B (70.24, 50-100 mL vs 194.44, 100-500 mL, P < .01). Time of weight bearing after operation in Group A is longer than Group B (50.70, 7-100 days vs 6.67, 4-14 days, P < .01). Incidence of complications 2 weeks after operation in Group A is less than Group B (14.12% vs 36.11%, P < .01). Mortality rates 12 months after operation in Group A is similar with Group B (13.10% vs 19.44%, P > .05). Harris Hip Score 12 months after operation in Group A is similar with Group B (64.64,0-91 points vs 64.41, 0-90 points, P > .05).Although BPH and PFNA have similar functional outcome and mortality rates 12 months after operation, BPH has more postoperative complications in elderly patients aged 85 years or more with ITFs, Bipolar Hemiarthroplasty should not be selected as the primary option for ITFs in elderly patients aged 85 years or more.


Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery.
Racial disparities have been demonstrated in many facets of health care, but a comprehensive understanding of who is most at risk for substandard surgical care of gastrointestinal tract cancers is lacking. To examine racial disparities in quality of care of patients with gastrointestinal tract cancers. This retrospective cohort study of patients with gastrointestinal tract cancer included the US population as captured in the National Cancer Database with a diagnosis from January 1, 2004, to December 31, 2017. Participants included 565 124 adults who underwent surgical resection of gastrointestinal tract cancers. Data were analyzed from June 21 to December 23, 2021. Race and site of cancer. Oncologic standard of care, as defined by negative resection margin, adequate lymphadenectomy, and receipt of indicated adjuvant chemotherapy and/or radiotherapy. Among 565 124 adult patients who underwent surgical resection of a gastrointestinal tract cancer, 10.9% were Black patients, 83.5% were White patients, 54.7% were men, and 50.7% had Medicare coverage. The most common age range at diagnosis was 60 to 69 years (28.5%). Longer median survival was associated with negative resection margins (87.3 [IQR, 28.5-161.9] months vs 22.9 [IQR, 8.8-69.2] months; P < .001) and adequate lymphadenectomies (80.7 [IQR, 25.6 to not reached] months vs 57.6 [IQR, 17.7-153.8] months; P < .001). After adjustment for covariates, Black patients were less likely than White patients to have negative surgical margins overall (odds ratio [OR], 0.96 [95% CI, 0.93-0.98]) and after esophagectomy (OR, 0.71 [95% CI, 0.58-0.87]), proctectomy (OR, 0.71 [95% CI, 0.66-0.76]), and biliary resection (OR, 0.75 [95% CI, 0.61-0.91]). Black patients were also less likely to have adequate lymphadenectomy overall (OR, 0.89 [95% CI, 0.87-0.91]) and after colectomy (OR, 0.89 [95% CI, 0.87-0.92]), esophagectomy (OR, 0.72 [95% CI, 0.63-0.83]), pancreatectomy (OR, 0.90 [95% CI, 0.85-0.96]), proctectomy (OR, 0.93 [95% CI, 0.88-0.98]), proctocolectomy (OR, 0.90 [95% CI, 0.81-1.00]), and enterectomy (OR, 0.71 [95% CI, 0.65-0.79]). Black patients were more likely than White patients not to be recommended for chemotherapy (OR, 1.15 [95% CI, 1.10-1.21]) and radiotherapy (OR, 1.49 [95% CI, 1.35-1.64]) because of comorbidities and more likely not to receive recommended chemotherapy (OR, 1.68 [95% CI, 1.55-1.82]) and radiotherapy (OR, 2.18 [95% CI, 1.97-2.41]) for unknown reasons. These findings suggest that there are significant racial disparities in surgical care of gastrointestinal tract cancers. Black patients are less likely than White patients to receive standard of care with respect to negative surgical margins, adequate lymphadenectomies, and use of adjuvant therapies. Both system- and physician-level reforms are needed to eradicate these disparities in health care.


A-to-I RNA editing shows dramatic up-regulation in osteosarcoma and broadly regulates tumor-related genes by altering microRNA target regions.
A-to-I RNA editing is a prevalent type of RNA modification in animals. The dysregulation of RNA editing has led to multiple human cancers. However, the role of RNA editing has never been studied in osteosarcoma, a complex bone cancer with unknown molecular basis. We retrieved the RNA-sequencing data from 24 primary osteosarcoma patients and 3 healthy controls. We systematically profiled the RNA editomes in these samples and quantitatively identified reliable differential editing sites (DES) between osteosarcoma and normal samples. RNA editing efficiency is dramatically increased in osteosarcoma, presumably due to the significant up-regulation of editing enzymes ADAR1 and ADAR2. Up-regulated DES in osteosarcoma are enriched in 3'UTRs. Strikingly, such 3'UTR sites are further enriched in microRNA binding regions of gene EMP2 and other oncogenes, abolishing the microRNA suppression on target genes. Accordingly, the expression of these tumor-promoting genes is elevated in osteosarcoma. There might be an RNA editing-dependent pathway leading to osteosarcoma. We expanded our knowledge on the potential roles of RNA editing in oncogenesis. Based on these molecular features, our work is valuable for future prognosis and diagnosis of osteosarcoma.


The neutrophil elastase-upregulated placenta growth factor promotes the pathogenesis and progression of periodontal disease.
Periodontal disease is a chronic inflammatory disease. Given its high prevalence, especially in aging population, the detailed mechanisms about pathogenesis of periodontal disease are important issues for study. Neutrophil firstly infiltrates to periodontal disease-associated pathogen loci and amplifies the inflammatory response for host defense. However, excessive neutrophil-secreted neutrophil elastase (NE) damages the affected gingival. In lung and esophageal epithelium, NE had been proved to upregulate several growth factors including placenta growth factor (PGF). PGF is an angiogenic factor with proinflammatory properties, which mediates the progression of inflammatory disease. Therefore, we hypothesize excessive NE upregulates PGF and participates in the pathogenesis and progression of periodontal disease. In gingival epithelial cells (GEC), growth factors array demonstrated NE-increased growth factors and further be corroborated by Western blot assay and ELISA. The GEC inflammation was evaluated by ELISA. In mice, the immunohistochemistry results demonstrated ligature implantation-induced neutrophil infiltration and growth factor upregulation. By multiplex assay, the ligature-induced proinflammatory cytokines level in gingival crevicular fluid (GCF) were evaluated. Finally, alveolar bone absorption was analyzed by micro-CT images and H & E staining. NE upregulated PGF expression and secretion in GEC. PGF promoted GEC to secret IL-1β, IL-6, and TNF-α in GCF In periodontal disease animal model, ligature implantation triggered NE infiltration and PGF expression. Blockade of PGF attenuated the ligature implantation-induced IL-1β, IL-6, TNF-α and MIP-2 secretion and ameliorated the alveolar bone loss in mice. In conclusion, the NE-induced PGF triggers gingival epithelium inflammation and promotes the pathogenesis and progression of periodontal disease.


Ceusia-Breast: computer-aided diagnosis with contrast enhanced ultrasound image analysis for breast lesions.
In recent years, contrast-enhanced ultrasonography (CEUS) has been used for various applications in breast diagnosis. The superiority of CEUS over conventional B-mode imaging in the ultrasound diagnosis of the breast lesions in clinical practice has been widely confirmed. On the other hand, there have been many proposals for computer-aided diagnosis of breast lesions on B-mode ultrasound images, but few for CEUS. We propose a semi-automatic classification method based on machine learning in CEUS of breast lesions. The proposed method extracts spatial and temporal features from CEUS videos and breast tumors are classified as benign or malignant using linear support vector machines (SVM) with combination of selected optimal features. In the proposed method, tumor regions are extracted using the guidance information specified by the examiners, then morphological and texture features of tumor regions obtained from B-mode and CEUS images and TIC features obtained from CEUS video are extracted. Then, our method uses SVM classifiers to classify breast tumors as benign or malignant. During SVM training, many features are prepared, and useful features are selected. We name our proposed method "Ceucia-Breast" (Contrast Enhanced UltraSound Image Analysis for BREAST lesions). The experimental results on 119 subjects show that the area under the receiver operating curve, accuracy, precision, and recall are 0.893, 0.816, 0.841 and 0.920, respectively. The classification performance is improved by our method over conventional methods using only B-mode images. In addition, we confirm that the selected features are consistent with the CEUS guidelines for breast tumor diagnosis. Furthermore, we conduct an experiment on the operator dependency of specifying guidance information and find that the intra-operator and inter-operator kappa coefficients are 1.0 and 0.798, respectively. The experimental results show a significant improvement in classification performance compared to conventional classification methods using only B-mode images. We also confirm that the selected features are related to the findings that are considered important in clinical practice. Furthermore, we verify the intra- and inter-examiner correlation in the guidance input for region extraction and confirm that both correlations are in strong agreement.


Influence of essential elements on cadmium uptake and toxicity in a unicellular green alga: the protective effect of trace zinc and cobalt concentrations.
Within the biotic ligand model (BLM) construct, major cations are considered to be simple competitors for metal binding to uptake sites and may offer some protection against metal-induced toxicity, but the influence of essential trace elements and cell preconditioning to different micronutrient concentrations on metal uptake and toxicity is considered negligible. To test these underlying assumptions, we monitored Cd uptake and toxicity in a green alga (Chlamydomonas reinhardtii) after long-term exposures (60 h) to a range of environmentally realistic free Zn(2+) , Co(2+) , Fe(3+) , Mn(2+) , Ca(2+) , and Cu(2+) concentrations buffered with nitrilotriacetic acid. A 200-fold increase in free [Mn(2+) ] as well as a 100-fold increase in free [Fe(3+) ] did not affect Cd uptake or toxicity, whereas a 50-fold increase in free [Ca(2+) ] effectively offered some protection, as predicted by the BLM. However, a 10-fold increase in free [Cu(2+) ] significantly enhanced Cd toxicity by a factor of approximately 2, whereas a 100-fold increase in free [Zn(2+) ] and [Co(2+) ] from 10(-11) to 10(-9) M significantly decreased Cd uptake and toxicity by more than twofold. These effects did not change with prior algal acclimation to different essential micronutrient concentrations. Low essential trace metal concentrations may strongly affect the uptake and toxicity of Cd in freshwater algae and should be taken into consideration in future developments of the BLM.


Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight loss and exercise on insulin sensitivity and restoration of normal fasting glucose in middle-aged and older women. Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010. 439 inactive, overweight/obese postmenopausal women. Women were assigned to: dietary weight loss (n=118); exercise (n=117); exercise+diet (n=117); or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. 12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR). A significant improvement in HOMA-IR was detected in the diet (-24%, p<0.001) and exercise+ diet (-26%, p<0.001) groups but not in the exercise (-9%, p=0.22) group compared with controls (-2%); these effects were similar in middle-aged (50-60 years) and older women (aged 60-75 years). Among those with impaired fasting glucose (5.6-6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were 2.5 (0.8, 8.4); 2.76 (0.8, 10.0); and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared with controls. Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women. This study is registered at Clinicaltrials.govNCT00470119.


Differential display of hippocampal and amygdaloid influences on hypothalamic evoked potentials.
Adult female rabbits with bipolar electrodes chronically implanted in the brain were employed to study the changes of the evoked potentials (EP) in the medial basal hypothalamus including the median eminence (ME), elicited by single hippocampal (HPC) or amygdaloid (AMYG) stimulus during EEG afterdischarge induced by electrical stimulation of the lattter two areas. In HPC seizures, the ME-EP from the HPC stimulation was extensively influenced in amplitude and peak-latency, the former decreased and the latter lengthened remarkably. On the other hand, the ME-EP from the AMYG stimulation did not show any noticeable changes either in amplitude or in peak-latency. During an AMYG seizure, the ME-EP from either the HPC or AMYG stimulation did not show any significant changes in amplitude or peak-latency. The results suggest that electrical activity of the neural pathways from the HPC to ME are very dependent on the excitability of the HPC, whereas those from the AMYG to ME seem variable, depending on the activity of the AMYG.


Comparative life cycle assessment of high-yield synthesis routes for carbon dots.
Carbon dots (CDs) are carbon-based nanomaterials with advantageous luminescent properties, making them promising alternatives to other molecular and nanosized fluorophores. However, the development of CDs is impaired by the low synthesis yield of standard fabrication strategies, making high-yield strategies essential. To help future studies to focus on cleaner production strategies, we have employed a Life Cycle Assessment (LCA) to compare and understand the environmental impacts of available routes for the high-yield synthesis of carbon dots. These routes were: (1) production of hydrochar, via hydrothermal treatment of carbon precursors, and its alkaline-peroxide treatment into high-yield carbon dots; (2) thermal treatment of carbon precursors mixed in a eutectic mixture of salts. Results show that the first synthesis route is associated with the lowest environmental impacts. This is attributed to the absence of the mixture of salts in the first synthesis route, which offsets its higher electricity consumption. Sensitivity analysis showed that the most critical parameter in the different synthetic strategies is the identity of the carbon precursor, with electricity being also relevant for the first synthesis route. Nevertheless, the use of some carbon precursors (as citric acid) with higher associated environmental impacts may be justified by their beneficial role in increasing the luminescent performance of carbon dots. Thus, the first synthesis route is indicated to be the most environmental benign and should be used as a basis in future studies aimed to the cleaner and high-yield production of carbon dots.


The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: A systematic review.
Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that nerves can actively infiltrate the tumour microenvironment and stimulate cancer cell growth. Therefore, the aim of the present study was to systematically review the identification and associations of perineural invasion and survival in patients with primary operable colorectal cancer. From initial search results of 912 articles, 38 studies were selected. Using H&E stains; five studies including 1835 patients reported on survival stratified by perineural invasion in colon cancer with weighted average detection rates of 26%; eleven studies including 3837 patients reported on rectal cancer with weighted average detection rates of 25% and; sixteen studies including 9145 patients reported on survival stratified by perineural invasion in colorectal cancer with weighted average detection rates of 17%. Using special techniques (S100), six studies including 1458 patients reported on the identification of perineural invasion in colorectal cancer. In comparison to H&E staining alone, the use of immunohistochemistry with S100 increased the detection of perineural invasion to approximately 70%. However, those studies did not examine the relationship with outcomes, so further research is required to establish the clinical significance of perineural invasion detected by immunohistochemistry. In conclusion, perineural invasion deserves special attention for improved prognostic stratification in patients with colorectal cancer. Further work is required to standardise pathology assessment and reporting of perineural invasion, in particular its definition, use of special stains and routine inclusion in pathology practice. Reliable assessment is required for investigations into mechanisms of perineural invasion, its role tumour spread and prognostic value.


The Transition into Young Adulthood: a Critical Period for Weight Control.
Emerging adulthood (age 18-25) represents a critical period for weight control: rate of weight gain is greatest during these years and the prevalence of overweight and obesity is estimated to be at least 40% among emerging adults. Unique behavioral, psychosocial, and cognitive risk factors among this population must be specifically addressed within weight management programs. We review extant treatment approaches, including lessons learned from the nascent literature specifically targeting this population. Lastly, we provide suggestions to inform future work in this area. The EARLY consortium comprises seven clinical trials targeting weight control in young adults age 18-35. Though these studies encompass a broader age range, two of the trials enrolled large numbers of 18-25-year-olds. Results from these trials and other recent pilot trials provide a foundation for next steps with respect to developing weight management interventions for emerging adults. The design of targeted weight control approaches for emerging and young adults has contributed to improved outcomes for this high-risk population. However, suboptimal engagement and variability in response pose challenges. Identifying and intervening on individual-level behavioral and psychological variables may enhance the effects of these adapted treatments.


Discriminating macromolecular interactions based on an impedimetric fingerprint supported by multivariate data analysis for rapid and label-free Escherichia coli recognition in human urine.
This manuscript presents a novel approach to address the challenges of electrode fouling and highly complex electrode nanoarchitecture, which are primary concerns for biosensors operating in real environments. The proposed approach utilizes multiparametric impedance discriminant analysis (MIDA) to obtain a fingerprint of the macromolecular interactions on flat glassy carbon surfaces, achieved through self-organized, drop-cast, receptor-functionalized Au nanocube (AuNC) patterns. Real-time monitoring is combined with singular value decomposition and partial least squares discriminant analysis, which enables selective identification of the analyte from raw impedance data, without the use of electric equivalent circuits. As a proof-of-concept, the authors demonstrate the ability to detect Escherichia coli in real human urine using an aptamer-based biosensor that targets RNA polymerase. This is significant, as uropathogenic E. coli is a difficult-to-treat pathogen that is responsible for the majority of hospital-acquired urinary tract infection cases. The proposed approach offers a limit of detection of 11.3 CFU/mL for the uropathogenic E. coli strain No. 57, an analytical range in all studied concentrations (up to 105 CFU/mL), without the use of antifouling strategies, yet not being specific vs other E.coli strain studied (BL21(DE3)). The MIDA approach allowed to identify negative overpotentials (-0.35 to -0.10 V vs Ag/AgCl) as most suitable for the analysis, offering over 80% sensitivity and accuracy, and the measurement was carried out in just 2 min. Moreover, this approach is scalable and can be applied to other biosensor platforms.