Dense-pattern multi-pass cavity based on spherical mirrors in a Z-shaped configuration for Raman gas sensing.
We report a dense-pattern multi-pass cavity (MPC) based on four spherical mirrors placed in a Z-shaped cavity configuration for improving the Raman signals from gases. The folding structure of the cavity causes dense patterns of spots, and at least 420 beams are reflected in the cavity. Raman spectra of ambient air, methane, and ethylene are recorded to demonstrate the performance of our apparatus. At atmospheric pressure, ppm-level detection limits of the gases are achieved with 10 s of exposure time. The Raman signal intensities of the gases show excellent linearity with the gases' partial pressures, which means that high-accuracy detection is also feasible.


Efficacy of a newly designed angulation-adjustable film holder for reducing cone-cutting errors and saving time in horizontal tube-shift technique by dental students.
To compare the cone-cutting error frequency and the X-ray cone alignment time in the horizontal tube-shift technique between the newly designed angulation-adjustable and the extension cone paralleling (XCP) holders, by dental students. Two film holders were assigned for a random test. The mandibular left first molar position of a laboratory phantom head was used. Intraoral periapical radiography was performed horizontally at right-angle, 20° mesial-, and 20° distal projections by fifth-year dental students (n = 41). The cone-cutting error frequency and the X-ray cone alignment time were measured and analyzed statistically at a significant level of p < 0.05. Using the two holders at right angle caused no significant difference (p > 0.05) in the cone-cutting error frequency or the X-ray cone alignment time. At the horizontal tube-shift angles, some significantly greater frequencies of cone-cutting errors at both 20° mesial (43.9%) and 20° distal (73.2%) shifts were detected in the XCP group, but none in the angulation-adjustable group. For X-ray cone alignment time at both 20° mesial and 20° distal shifts, the XCP group spent a significantly longer time (p < 0.05) than the angulation-adjustable group. The usages of the angulation-adjustable holder in the horizontal tube-shift technique resulted in none of the cone-cutting error and a significant reduction of time for the X-ray cone alignment, when compared to those of the XCP instrument. The angulation-adjustable holder effectively reduced cone cutting error and treatment time, both of which were beneficial to the patients and the dental personnel.


Identification of Chinese green tea (Camellia sinensis) marker metabolites using GC/MS and UPLC-QTOF/MS.
Tea is one of the most widely consumed aromatic beverages in the world because of its taste and flavor, as well as due to many potential health beneficial properties. Metabolomics focuses on an in-depth analysis of all metabolites in living organisms. In this study, 29 primary metabolites and 25 secondary metabolites were identified using GC/MS and UPLC-QTOF/MS, respectively. Further, PCA analysis showed conspicuous discrimination for the ten varieties of green tea with metabolite profiling. Among them, organic acids, amino acids, flavan-3-ols, and flavonol glycosides varied greatly through checking the VIP values of the PLS-DA model. Moreover, the intrinsic and/or extrinsic factors characterizing each type of green tea were also discussed. The chemical component marker derived here should be used as an important detection index, while evaluating the tea quality, as well as while establishing the tea quality standard. The online version contains supplementary material available at 10.1007/s10068-021-00970-4.


Similarities in the heavy and light chains of tetanus toxin suggested by their amino acid compositions.
Quantitative comparison of the amino acid compositions of the heavy and light chains of tetanus toxin by the method of Cornish-Bowden [(1983) Methods Enzymol. 91, 60-75)] suggests strongly that there is sequence homology between the two chains and that the heavy chain has two similar halves. Examination (by electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulphate) of peptides produced from the chains by proteolytic cleavage supports this idea.


A Pascal program for weighted least squares regression on a microcomputer.
Weighted least-squares regression has been programmed in Pascal for a microcomputer. A double precision Pascal compiler and the Motorola 6809 assembler produce a fast machine-code program occupying 22,000 bytes of memory when appended to the Pascal run-time module. Large data sets fit in the remaining memory. A regression with 72 observations and 24 parameters runs in 7 min, excluding optional print out of large matrices. The maximum dimensions of the design matrix, X, can be altered by modifying two Pascal constants. Minor changes to the Pascal source program will make it compatible with other Pascal compilers. The program optionally orthogonalises the X matrix to detect linearly-dependent columns in X, and/or generate orthogonal parameter estimates. After orthogonalizing X and fitting the model, the parameter estimates for the original X can be retrieved by the program. Regressions on a repeatedly reduced model are performed through elimination of columns in X until the minimum adequate model is obtained.


Localization of Trk neurotrophin receptor-like proteins in avian primary lymphoid organs (thymus and bursa of Fabricius).
The avian thymus and bursa of Fabricius are the specific organs where the maturation and differentiation of T- and B-lymphocytes, respectively, take place. In the mammalian lymphoid organs mRNAs of the neurotrophins and their receptors have been identified but their localization at the protein level remains still unknown. This study was undertaken to analyze the localization of the Trk family of tyrosine kinase receptors in the avian primary lymphoid organs (thymus and bursa of Fabricius) during the posthatching development using immunohistochemistry. These proteins serve as essential constituents of the high affinity receptors for neurotrophins. In the thymus of all groups of age specific immunoreactivity (IR) was observed for all three Trks: TrkA-like IR was found labelling medullary epithelial cells and a subpopulation of cortical epithelial cells; TrkB-like IR was found in the medullar dendritic cells and cortical macrophages; TrkC-like IR labelled the cortical epithelial cells and scattered medullar clusters of epithelial cells (including Hassal's corpuscles). Quantitative analysis revealed age-dependent decrease in the area occupied by TrkA-like IR in the cortex, and age-dependent increase in the medulla; no changes were detected in the area occupied by TrkB-like IR; the TrkC-like immunoreactive cells increase from 7 to 30 days and then decrease. Regarding to the bursa of Fabricius, TrkA-and TrkC-like IR were exclusively found in the epithelial cells of the follicle associated and the interfollicular epithelia, as well as TrkC-like IR in some medullary reticular epithelial cells of adult animals. Nevertheless, TrkB-like IR labelled extrafollicular unidentified cells in 7 days old animals, and the follicular secretory dendritic cells at 30 and 60 post-hatching. The area occupied by the medullary TrkB-like IR cells increased between 30 and 60 days. No immunostaining of lymphocytes was observed for any of the assessed antigens. The blood vessels of both the thymus and the bursa of Fabricius were immunoreactive for TrkA- and TrkC-like proteins. The present results provide evidence for the localization of Trks in the non-lymphoid cells (epithelial and dendritic) of the avian primary lymphoid organs, suggesting a role for neurotrophins in these cells. Moreover, the selective cell localization of each Trk protein, and the absence of apparent overlapping, claims for a differential role of the specific Trk ligands. Whether or not these findings have functional relevance for T- and B-lymphocytes processing in avian primary lymphoid organs is discussed.


Murine monoclonal antibodies directed to the human histo-blood group A transferase (UDP-GalNAc:Fuc alpha 1----2Gal alpha 1----3-N-acetylgalactosaminyltransferase) and the presence therein of N-linked histo-blood group A determinant.
Mouse MAbs (WKH-1 through -3) to the human histo-blood group A glycosyltransferase (Fuc alpha 1----2Gal alpha 1----3 galactosaminyltransferase) were established by immunization with the purified native A transferase protein. Hybridomas were selected on the basis of solid-phase reactivity with the purified native A transferase, cell immunofluorescence and immunoprecipitation of transferase activity, and absence of reactivity with blood group ABH carbohydrate determinants. Three MAbs, thus selected, were found most likely to react with the protein epitopes unrelated to carbohydrate epitopes of purified A transferase. The MAbs reacted with cells having high A transferase activity and immunoprecipitated the A transferase activity as well as the 40,000 MW iodinated transferase protein. The antibodies were shown, however, to immunoprecipitate and partially inhibit not only A1 and A2 but also B transferase activity from plasma and A transferase from human lung, and to react with B cells expressing B transferase, thus indicating a cross-reactivity with B transferase. In contrast, they showed no reactivity with various cells having the O phenotype and did not immunoprecipitate the A transferase from porcine submaxillary glands or the alpha 1----2fucosyltransferase from Colo205 cells. The purified A glycosyltransferase was found to carry blood group A carbohydrate determinants by immunochemical detection with a panel of anti-carbohydrate MAbs. These determinants are believed to be N-linked, since treatment of the purified A transferase with N-glycanase removed activity. Immunohistological studies of three epithelial tissues showed that the antibodies stained the Golgi area of cells in epithelia from A and B, but not O, individuals.


Mechanism of pulsus bisferiens in thoracoabdominal thoracic aneurysms: Insights from wave intensity analysis.
Aortic pulsatile hemodynamics are important in various clinical conditions. Whereas the importance of wave reflections of the closed type in pulsatile hemodynamics has been extensively studied, less is known about the impact of reflections of the open type, in which reflected waves changes both direction and type (compression vs suction) compared to the incident wave. In this report, we present careful pulsatile hemodynamic analyses of a case in which prominent reflections of the open type occur in a patient with a thoracoabdominal aortic aneurysm, causing a highly abnormal proximal aortic and peripheral arterial hemodynamic pattern, known as pulsus bisferiens. Wave intensity analysis of central pressure-flow data demonstrated an early systolic forward-traveling compression wave followed by a prominent late systolic forward-traveling expansion wave, along with an abnormal prominent late systolic/early diastolic backward-traveling compression wave which produced a sharp rise in diastolic pressure, and was responsible for the pulsus bisferiens pattern.


High-performance liquid chromatography of azobenzene derivatives with spectrophotometric and electrochemical detection.
The chromatographic behaviour of azobenzene and fourteen of its derivatives was studied by reversed-phase high-performance liquid chromatography with a C18 stationary phase. The optimal composition of the mobile phase is 9:1 methanol-0.01 M aqueous sodium dihydrogen phosphate which is 0.0002 M in ethylenediaminetetraacetic acid, with a pH of 4.5. The solutes can be detected spectrophotometrically, voltammetrically or polarographically. Spectrophotometric measurement in the visible range is more sensitive than in the UV range (detection limits of 0.04-0.1 ng at 410 nm compared with 0.3-0.5 ng at 265 nm). Voltammetric detection is highly sensitive for hydroxy and amino derivatives [detection limits 0.02-0.09 ng at +0.8 V (Ag-AgCl)], whereas for other substances the detection limits are a few nanograms. Polarographic detection is the least sensitive [detection limits 4-8 ng at -0.6 V (Ag-AgCl)]. All the calibration graphs exhibit good linearity, but spectrophotometric detection yields a wider linear dynamic range. Voltammetric detection is more precise at low solute concentrations (relative standard deviations of the peak heights 0.5-1.0% and 1.0-1.5% for voltammetric and spectrophotometric detection, respectively, with amounts of solute from 1 to 10 ng).


[Physiopathology of ischemic transitory attacks in the vertebro-basilar region. II. Physiopathological and clinical aspects].
Hemodynamic and metabolic factors of regional cerebral blood flow regulation are analyzed, and pathophysiology and clinical aspects of transient ischemic attacks of vertebro-basilar system are discussed.


Effects of a group activity-based motivational enhancement therapy program on social media addictive behaviors among junior high school students in Thailand: a cluster randomized trial.
This study aimed to assess the effects of a group activity-based motivational enhancement therapy (GA-MET) program on social media addictive behaviors among junior high school students. This cluster randomized trial was performed in 245 junior high school students who used social media in the lower part of northeast Thailand. The GA-MET program group and the control group sessions lasted 8 weeks and were followed up 4 weeks later. The addictive social media behaviors, average duration of social media usage during weekdays and weekends (hours/day), child behaviors, self-esteem, and depression were investigated using a self-reported questionnaire. Multivariable linear regression was used to compare the mean and 95% CIs between two groups. The GA-MET program significantly decreased the average duration of social media usage during weekdays and weekends (hours/day) (-1.27, 95% CI: -2.18,-0.37 and -1.25, 95% CI: -2.22, -0.29, respectively), emotional behavior (-0.69, 95% CI: -1.18, -0.19), and depression (-4.03, 95% CI: -6.07, -1.99) in the treated group compared to the control group. The GA-MET program could reduce the risk of social media addictive behaviors in junior high school students in Thailand by decreasing time spent on social media, emotional behaviors, and depression.


Alcohol consumption and suicide rate: A cross-sectional analysis in 183 countries.
The age-standardized suicide rate and per capita alcohol consumption from 183 countries were acquired, and its relationship with per capita alcohol consumption was examined by the regression analysis. The positive associations between per capita alcohol consumption and the suicide rate were found among males and females in all income groups of countries. Compared with other environmental factors, controlling alcohol consumption has a distinct target and can be feasible and effective for reducing suicides. Health policy makers should keep in mind that alcohol consumption is costing lives not just by long-term physical ailments but also by making people vulnerable to suicide.


Towards a cross-level understanding of Bayesian inference in the brain.
Perception emerges from unconscious probabilistic inference, which guides behaviour in our ubiquitously uncertain environment. Bayesian decision theory is a prominent computational model that describes how people make rational decisions using noisy and ambiguous sensory observations. However, critical questions have been raised about the validity of the Bayesian framework in explaining the mental process of inference. Firstly, some natural behaviours deviate from Bayesian optimum. Secondly, the neural mechanisms that support Bayesian computations in the brain are yet to be understood. Taking Marr's cross level approach, we review the recent progress made in addressing these challenges. We first review studies that combined behavioural paradigms and modelling approaches to explain both optimal and suboptimal behaviours. Next, we evaluate the theoretical advances and the current evidence for ecologically feasible algorithms and neural implementations in the brain, which may enable probabilistic inference. We argue that this cross-level approach is necessary for the worthwhile pursuit to uncover mechanistic accounts of human behaviour.


Menopausal hormone therapy and sleep-disordered breathing: evidence for a healthy user bias.
Observational studies suggest that menopausal hormone therapy protects against sleep-disordered breathing, but such findings may be biased by a "healthy user effect." When the Women's Health Initiative Study reported in 2002 that estrogen-progestin therapy increases heart disease risk, many women discontinued hormone therapy. We investigate healthy user bias in the association of hormone therapy with sleep-disordered breathing in the Sleep in Midlife Women Study. A total of 228 women aged 38 to 62 years were recruited from the Wisconsin Sleep Cohort Study. They underwent polysomnography to measure apnea-hypopnea index, at home semiannually from 1997 to 2006, and in the sleep laboratory every four years (n = 1828 studies). Hormone therapy was recorded monthly. Linear models with empirical standard errors regressed logarithm of apnea-hypopnea index on hormone use with a pre- or post-July 2002 interaction, adjusting for menopause and age. The association of hormone therapy and sleep-disordered breathing was heterogeneous (P < .01); apnea-hypopnea index among users was 15% lower in the early period (95% confidence interval, -27% to -1%), but similar to nonusers in the late. Hormone therapy was negatively associated with sleep-disordered breathing only until the Women's Health Initiative results were publicized. Hormone therapy may have been a marker for healthfulness in the early period, creating a spurious association with sleep-disordered breathing.


[Monoclonal antibody preparation and identification of vascular endothelial growth factor 165 expressed in vitro].
To prepare a monoclonal antibody against human vascular endothelial growth factor (VEGF165), for further study the VEGF165 in the tumorigenesis, tumor cell migration and the tumor cells escape from the immune response. VEGF165 gene was cloned from the human umbilical vein endothelial cells (HUVEC) by RT-PCR, and then cloned into the pGEX-6P1, constructed the prokaryotic expression of pGEX-6P1-VEGF165. The fusion -protein of VEGF165 was expressed in E.coli (BL21) induced by the 1.0 mmol/L IPTG at 37DegreesCelsius after 4 h. The fusion-protein was purified by the MicroSpin GST purification kit for immunized the BALB/c mouse. The monoclonal antibodies (mAbs) against the VEGF165 were prepared by hybridoma technique, and ELISA and Western blot identified their immunoglobulin subclass and specificity. And we used the inhibition the embryo angiogenesis assay, inhibition the HUVEC migration assay and inhibition the HUVEC tubule information assay to study the bioactivity of the mAbs of VEGF165. The sequence of the VEGF165 is agreed to the GenBank, and we obtained five species VEGF165 mAbs, and the titer of the antibody is high, and we named, they are 5A6, 3F5, 6H3, 7D10 and 7A10. Our study showed that the 5A6, 3F5, 6H3, 7D10 were classified to IgG2a, 7A10 was classified to IgG2b, and the light chain is k.Meanwhile the purified mAbs inhibited formation of chicken embryo blood vessels, and inhibited tubule formation of the HUVEC and inhibited migration of the HUVEC. mAbs against human VEGF165 have the effective bioactivity, which would play a significant role for further study the mechanism of VEGF165.


Acupuncture protected cerebral multi-infarction rats from memory impairment by regulating the expression of apoptosis related genes Bcl-2 and Bax in hippocampus.
Vascular dementia (VaD) is the second most common cause of dementia in the world today. In this paper, we observed the effect of acupuncture on memory impairment, apoptosis and expression of Bcl-2 and Bax in hippocampus of cerebral multi-infarction rats. The results indicated that acupuncture significantly improved memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time in the target quadrant. Meanwhile, based on the observation in hippocampal CA1 region through methods of the terminal deoxynucleotidyl transferase nick end labeling (TUNEL), immunohistochemistry and in situ hybridization, acupuncture decreased the number of apoptotic cells and expression of the proapoptotic Bax gene, on the contrary, it increased expression of the antiapoptotic gene Bcl-2. The result of the research suggested that acupuncture can exert antiapoptotic effect through counter-regulating Bcl-2 and Bax gene expression.


Reversal of multidrug resistance by stimuli-responsive drug delivery systems for therapy of tumor.
Multidrug resistance (MDR) is a major obstacle to successful cancer therapy, especially for chemotherapy. The new drug delivery system (DDS) provides promising approaches to reverse MDR, for which the poor cellular uptake and insufficient intracellular drug release remain rate-limiting steps for reaching the drug concentration level within the therapeutic window. Stimulus-coupled drug delivery can control the drug-releasing pattern temporally and spatially, and improve the accumulation of chemotherapeutic agents at targeting sites. In this review, the applications of DDS which is responsive to different types of stimuli in MDR cancer therapy is introduced, and the design, construction, stimuli-sensitivity and the effect to reverse MDR of the stimuli-responsive DDS are discussed.


shibire, a neurogenic mutant of Drosophila.
Embryos of the temperature-sensitive mutant shibirets 1 were given short exposures to the restrictive temperature during the stage when neuroblasts segregate from the presumptive epidermis. The resulting lethal phenotype, expansion of the nervous system at the expense of the epidermis, is characteristic of a group of mutants called neurogenic mutants. Exposures as short as 20 min were sufficient to promote the neurogenic phenotype. Cell masses from heat-pulsed embryos could be cultured in vivo as tumorous masses which retained some characteristics of neural tissue. An examination of the neurogenic region from heat-pulsed embryos revealed numerous packets of extracellular vesicles and coated pits blocked in endocytosis.


Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis.
Fast food consumption is associated with biomarkers of ortho-phthalates exposures. However, the chemical content of fast food is unknown; certain ortho-phthalates (i.e., di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP)) have been phased out and replaced with other plasticizers (e.g., dioctyl terephthalate (DEHT)). We conducted a preliminary study to examine ortho-phthalate and replacement plasticizer concentrations in foods and food handling gloves from U.S. fast food restaurants. We obtained hamburgers, fries, chicken nuggets, chicken burritos, cheese pizza (n = 64 food samples) and gloves (n = 3) from restaurants and analyzed them for 11 chemicals using gas chromatography mass spectrometry. We found DEHT at the highest concentrations in both foods (n = 19; median = 2510 µg/kg; max = 12,400 µg/kg) and gloves (n = 3; range: 28-37% by weight). We detected DnBP and DEHP in 81% and 70% of food samples, respectively. Median DEHT concentrations were significantly higher in burritos than hamburgers (6000 µg/kg vs. 2200 µg/kg; p < 0.0001); DEHT was not detected in fries. Cheese pizza had the lowest levels of most chemicals. To our knowledge, these are the first measurements of DEHT in food. Our preliminary findings suggest that ortho-phthalates remain ubiquitous and replacement plasticizers may be abundant in fast food meals. A selection of popular fast food items sampled in this study contain detectable levels of replacement plasticizers and concerning ortho-phthalates. In addition, food handling gloves contain replacement plasticizers, which may be a source of food contamination. These results, if confirmed, may inform individual and regulatory exposure reduction strategies.


Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell.
Methanol extract from cultured Scutellaria baicalensis cells inhibited the proliferation of human monocytic leukemia cell line THP-1 and human osteogenic sarcoma cell line HOS. The inhibitory effects of baicalin, baicalein and wogonin, the three major flavonoids contained in the extract, were studied. It should be noted that wogonin did not show the inhibitory effect on human fetal lung normal diploid cell line TIG-1, as compared to the inhibition observed in cancer cells. Physiological analyses in THP-1 cells showed that wogonin induced cell cycle arrest at G(2)/M phase and apoptosis. This is the first report discovering a cancer-specific apoptosis-inducing activity of wogonin.


Intravenous vitamin injections: where is the evidence?
The body needs small daily quantities of vitamins and minerals, which are usually obtained from the diet. Intravenous vitamins are used for a few serious medical conditions (eg, malabsorption syndromes with severe vitamin depletion, Wernicke's encephalopathy or critical illness). Intravenous drips containing high doses of various vitamins and minerals (eg, the so-called 'Myers' cocktail') have been promoted in popular culture to 'reduce stress', 'increase energy' or 'boost immunity', with claims that the intravenous route allows faster absorption of vitamins into the bloodstream than if they are taken orally. There is a lack of high-quality evidence to suggest that high-dose vitamin infusions are necessary or offer any health benefit in the absence of a specific vitamin deficiency or medical condition. There may be harms from taking high (non-physiological) quantities of some vitamins and minerals. Licensed forms of injectable vitamins that are prescription-only medicines should not be advertised to the public and should only be supplied and administered by appropriately qualified healthcare professionals.


[Longitudinal Wirsung gastrostomy in the surgical management of chronic pancreatitis].
The longitudinal pancreatico-jejunostomy is a commonly used procedure in the management of the chronic pancreatitis with dilated pancreatic duct (Wirsung), however the drainage of the dilated pancreatic duct is realizable with longitudinal Wirsungo-gastrostomy to. We present one clinical case of chronic pancreatitis with dilated pancreatic duct, where the pancreatic drainage was realized with an anastomosis between the dilated Wirsung duct and the posterior wall of the stomach (longitudinal Wirsungo-gastrostomy). One year after Wirsungo-gastrostomy (postoperative reevaluation of the patient) a general well condition without subjective accuses, ponderal increase and stabile glucidic metabolism was found. The Wirsungo-gastrostomy could represent an alternative procedure in the management of the chronic pancreatitis with dilated pancreatic duct.


Association Between Relative Anemia and Early Functional Recovery After Severe Traumatic Brain Injury (TBI).
Severe traumatic brain injury is associated with a multi-systemic response and changes in metabolic demand. Patients requiring intracranial pressure monitoring or cerebrospinal fluid diversion, often signifies a greater severity of injury. For this group, the association between RBC transfusion, transfusion thresholds, and clinical recovery is unknown. In this study, we studied the association between transfusion and clinical recovery for severe traumatic brain injury patients requiring external ventricular drain or intracranial pressure monitor placement. Eighty-nine patients with a primary diagnosis of traumatic brain injury requiring implantation of either an intracranial pressure monitor or external ventricular drainage device were identified. All patients were managed in a Level 1 Trauma facility by board-certified neuro-intensive care practitioners for the course of their intensive care unit duration. The correlation between transfusion and clinical recovery, defined by change in Glasgow Coma Scale was assessed. Thirty-four patients required surgical decompression, and 56.18 % of the cumulative cohort were transfused during admission. Overall, transfusion was not associated with significant clinical recovery (change in GCS > 3) for Hgb threshold of 7 mg/dL (<3, 29.03 vs. ≥3, 37.93 %; p = 0.49), nor for higher stratifications (8 mg/dL, p = 0.63; 9 mg/dL, p = 0.79, 10 mg/dL, p = 1). For patients who required transfusions at thresholds ≥8 mg/dL, there was a positive association with decreased length of hospitalization, [p = 0.01; <8 mg/dL: 22 (12-33), ≥8 mg/dL: 14 (7.75-20)] [median (IQR)]. Similarly, length of ICU stay was shorter for patients transfused at thresholds ≥9 mg/dL, (p = 0.02). From our studies, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. In patients admitted for primary severe traumatic brain injury, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a noticeable decrease in length of hospitalization for patients with transfusion thresholds of Hgb ≥ 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population.


Cytochalasin B binding to rabbit proximal tubular basolateral membranes.
Cytochalasin B binds to the Na+-independent D-glucose transporter in non-renal tissues. We have shown previously that the Na+-independent D-glucose transporter of the rabbit renal proximal tubular cell is localized exclusively in the basolateral membrane. To determine whether cytochalasin B binds to this renal transporter we measured binding of [3H]cytochalasin B to proximal tubular basolateral membranes isolated from rabbit kidneys. A steady state of binding is reached by 15 minutes at 20 degrees C over a concentration range of 0.01 to 50 microM. Non-linear regression analysis of cytochalasin B binding from 0.01 to 20 microM plotted according to Scatchard reveals two classes of binding sites with Kd 5.88 x 10(-8) M, Bmax 16.1 pmol/mg protein; and Kd 5.62 x 10(-5) M, Bmax 2816 pmol/mg protein. [3H]cytochalasin B (0.1 microM) binding to basolateral membranes is a reversible process; it is displacable by excess unlabeled cytochalasin B with a time course similar to binding of [3H]cytochalasin B. Binding of [3H]cytochalasin B is inhibited by 500 mM D-glucose (21%), 2-deoxy-D-glucose (57%) and 3-O-methyl-D-glucose (64%), but not by L-glucose. [3H]cytochalasin B binding is reduced 71% by 0.1 mM phloretin, but only 26% by 0.1 mM phlorizin. Such substrate specificity and inhibitor sensitivity are similar to those previously demonstrated in non-renal tissues by others as well as in rabbit renal proximal tubular basolateral membranes by us. Our data suggest that cytochalasin B binds to the Na+-independent D-glucose transporter or a component of the transporter in the renal proximal tubular basolateral membrane.


Comparison of the specificity of antibodies to VAR2CSA in Cameroonian multigravidae with and without placental malaria: a retrospective case-control study.
Antibodies (Ab) to VAR2CSA prevent Plasmodium falciparum-infected erythrocytes from sequestrating in the placenta, i.e., prevent placental malaria (PM). The specificity of Ab to VAR2CSA associated with absence of PM is unknown. Accordingly, differences in the specificity of Ab to VAR2CSA were compared between multigravidae with and without PM who had Ab to VAR2CSA. In a retrospective case-control study, plasma collected from Cameroonian multigravidae with (n = 96) and without (n = 324) PM were screened in 21 assays that measured antibody levels to full length VAR2CSA (FV2), individual VAR2CSA DBL domains, VAR2CSA domains from different genetic backgrounds (variants), as well as proportion of high avidity Ab to FV2. Multigravidae with and without PM had similar levels of Ab to FV2, the six VAR2CSA DBL domains and different variants, while the proportion of high avidity Ab to FV2 was significantly higher in women without PM at delivery (p = 0.0030) compared to women with PM. In a logistic regression model adjusted for gravidity and age, the percentage of high avidity Ab to FV2 was associated with reduced likelihood of PM in multigravidae. A 5 % increase in proportion of high avidity Ab to FV2 was associated with a nearly 15 % lower likelihood of PM. Ab avidity to FV2 may be an important indicator of immunity to PM.


Imbalance between T helper 17 and regulatory T cell subsets plays a significant role in the pathogenesis of systemic sclerosis.
Systemic sclerosis (SSc) is a rare autoimmune disease that is characterized by fibrosis, inflammation, and vasculopathy of the skin and internal organs. The etiopathogenesis of SSc remains unclear. However, the pivotal role of T lymphocytes with an aberrant immune response in SSc is well established. Among T cells, IL-17-producing helper T (Th17) cell and regulatory T (Treg) cell subsets have recently been found to play crucial roles in SSc pathogenesis. Generally speaking, Th17 cell subsets up-regulate inflammation, fibrosis, and autoimmunity, which are present in SSc, while Treg cell subsets have an immunosuppressive function and resist the immunological performance of Th17 cells. Up-to-date evidence has pointed out that the imbalance and abnormal functions of Th17/Treg cells may contribute to SSc. Therefore, this review aims to summarize the current understanding of the vital cytokines and signaling pathways that are involved in Th17/Treg differentiation and functions, and their roles in the pathogenesis of SSc, thus providing novel insights about targeting the Th17/Treg balance as a potential therapy for SSc treatment in the near future.


Quantitative Proteomic Analysis Reveals Molecular Adaptations in the Hippocampal Synaptic Active Zone of Chronic Mild Stress-Unsusceptible Rats.
While stressful events are recognized as an important cause of major depressive disorder, some individuals exposed to life stressors maintain normal psychological functioning. The molecular mechanism(s) underlying this phenomenon remain unclear. Abnormal transmission and plasticity of hippocampal synapses have been implied to play a key role in the pathoetiology of major depressive disorder. A chronic mild stress protocol was applied to separate susceptible and unsusceptible rat subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation coupled with tandem mass spectrometry was performed to identify differential proteins in enriched hippocampal synaptic junction preparations. A total of 4318 proteins were quantified, and 89 membrane proteins were present in differential amounts. Of these, SynaptomeDB identified 81 (91%) having a synapse-specific localization. The unbiased profiles identified several candidate proteins within the synaptic junction that may be associated with stress vulnerability or insusceptibility. Subsequent functional categorization revealed that protein systems particularly involved in membrane trafficking at the synaptic active zone exhibited a positive strain as potential molecular adaptations in the unsusceptible rats. Moreover, through STRING and immunoblotting analysis, membrane-associated GTP-bound Rab3a and Munc18-1 appear to coregulate syntaxin-1/SNAP25/VAMP2 assembly at the hippocampal presynaptic active zone of unsusceptible rats, facilitating SNARE-mediated membrane fusion and neurotransmitter release, and may be part of a stress-protection mechanism in actively maintaining an emotional homeostasis. The present results support the concept that there is a range of potential protein adaptations in the hippocampal synaptic active zone of unsusceptible rats, revealing new investigative targets that may contribute to a better understanding of stress insusceptibility.


Acute and subchronic toxicity of the antitumor agent rhodium (II) citrate in Balb/c mice after intraperitoneal administration.
This study aimed to investigate potential acute and subchronic toxicity of rhodium (II) citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg) was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%), 53.8 (50%), 26.9 (25%) or 13.8 mg/kg (12.5%). Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50) could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg) were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg) and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.


Efficacy of focal applications of a mycoinsecticide to control Aedes aegypti in Central Brazil.
Entomopathogenic fungi can achieve important innovative outcomes for integrated mosquito control especially of Aedes aegypti, the key vector of arboviruses to humans in the tropics and subtropics. This study sought to design and to develop a simple dissemination device to attract and to infect gravid A. aegypti adults with a granular formulation of the ascomycete Metarhizium humberi IP 46, and to validate this device in the laboratory as well as in semi-field and field conditions. Hydrogel (polyacrylamide potassium polyacrylate) was confirmed to be a suitable substitute for water used in the device that attracted gravid females under field conditions. Females laid eggs on black polyethylene terephthalate carpet fixed in the device that also proved to be a suitable substrate for a granular formulation of fungal microsclerotia and/or conidia. The plastic device (29.5 cm high) was divided into a lower closed compartment with a water reservoir and an upper, laterally open but covered compartment with continuously hydrated gel and the fungal formulation attached to the carpet. The uppermost compartment permitted free circulation of mosquito adults. The device attracted both male and female A. aegypti. The fungal formulations of IP 46 propagules tested in the device were effective against adults in laboratory, semi-field, and field settings. Findings in the laboratory, semi-field, and especially in field conditions strengthen the value and utility of this innovative device for focal applications of a mycoinsecticide against this important mosquito vector.Key points• Low-cost and simple disseminating device for focal control of Aedes aegypti.• Granulized Metarhizium humberi IP 46 and hydrogel yield extended control.• Findings in field tests strengthen benefit of the device for focal application.


Perventricular device closure of patent ductus arteriosus: a secondary chance.
Transcatheter closure is the mainstay of treatment for patent ductus arteriosus (PDA) in the pediatric patient but it is technically challenging and does not always succeed, especially in a younger age child with a large PDA. We present a technique of using a transesophageal echocardiogram-guided minimally invasive perventricular closure for the pediatric patient with a large PDA who failed transcatheter closure.


Synthesis of 8-azidooctyl glycoside derivatives of the O-chain repeating unit of Escherichia coli O9a lipopolysaccharide and a methylated analog.
Described is the synthesis of 8-azidooctyl glycoside derivatives of the Escherichia coli serotype O9a O-chain tetrasaccharide repeating unit and the terminal tetrasaccharide motif in this polysaccharide, which contains a methyl group on O-3 of the distal mannopyranose residue. The assembly of these compounds involved the sequential addition of monosaccharide residues from the reducing to the nonreducing end of the molecule using glycosyl trichloroacetimidate donors. Both compounds were initially prepared as p-methoxyphenyl glycosides, which were converted to the corresponding 8-azidooctyl derivatives at a late stage in the synthesis.


[The ergo-ophthalmological problems raised by work at video terminals].
The paper reports a study on the involvement of the visual system during work at video terminal. The results of the investigations on a group of operators in a computation centre were used for describing an optimum anatomicofunctional visual type for work at video terminal and the hygiene rules to be observed during work at the computer screen.


Radiation exposure and the orthopedic surgeon's hand: Measurement of the equivalent dose over 13 months.
Exposure to ionizing radiation in the operating room is governed by practical prevention and protection measures on the international, national and local levels. We evaluated the equivalent dose to the hand of an orthopedic surgeon over 13 months. An orthopedic surgeon wore a ring dosimeter on the ring finger of his right hand for all surgical procedures requiring intraoperative fluoroscopy between March 2014 and April 2015. Monthly doses were evaluated by the IRSN over the study period. The number and type of procedures were compiled as well as the type of fluoroscopy unit used. Four hundred procedures were performed during this period, including 182 with fluoroscopy. The equivalent cumulative dose at the hand was 4,75 mSv. No correlation was found with the type of procedure or type of fluoroscopy unit (conventional or mini C-arm). Equivalent doses were below the annual regulatory limit in France of 500 mSv. These results are consistent with those reported in the literature. However, recent studies have noted that both younger surgeons in training and more experienced surgeons must remember to use radiation protection measures.


Pituitary intracisternal granule formation during the estrus cycle of the rat.
An ultrastructural study of the anterior pituitaries of cycling rats reveals changes in the ultrastructure of the gonadotrophs during the afternoon of proestrus when the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is high. The rough endoplasmic reticulum cisternae become greatly dilated, forming extensive channels which are continuous with the perivascular space and provide an increased surface for the release of hormones. Granules and cytoplasmic islands of granules are seen in these spaces. Such changes are not observed during diestrus and early proestrus when the release of FSH/LH is low. The data indicate that intracisternal granule formation is an important mechanism by which anterior pituitary cells respond to increased hormonal requirements.


Current behavioral health and cognitive screening practices in pediatric epilepsy.
Initiatives such as the Epilepsy Learning Healthcare System continue to advocate for standardized care and shared outcome data. Therefore, the current project aim was to gather information from epilepsy healthcare professionals, behavioral health professionals in particular, regarding their behavioral health and cognitive screening practices in pediatric patients with epilepsy. Information obtained will be used to assist in the development of new educational programs and platforms in the American Epilepsy Society (AES) and to inform the development of guidelines for behavioral healthcare of patients with pediatric epilepsy. Twenty-five AES members representing 25 unique epilepsy programs across the United States participated in the survey. Findings are described in terms of three focus areas: (1) Systems, (2) Assessment, and (3) Intervention. Over 80% of respondents surveyed reported that they do conduct formal screenings, most commonly to determine if further evaluation is indicated (81%), inform treatment decisions (57.1%), and for developmental surveillance (33.3%). Assessment methods were fairly evenly split between nonstandardized informal questions (50%) and evidence-based broadband measures, with the Behavior Assessment System for Children (BASC), 2nd or 3rd Editions (40%) most commonly used. If behavioral health concerns are identified, referrals are often made for psychotherapy (48% in-house; 80% community-based), psychiatry (68% in-house; 48% community-based), and cognitive testing (88% neuropsychological testing; 36% for psychoeducational testing). Thirty-two percent refer for psychotropic medication management. According to this survey, a number of epilepsy centers and clinics incorporate behavioral health screening; however, there is significant variability in assessments/measures used, who is administering them, and their purpose in the trajectory of treatment. These findings emphasize the need for standardization across centers in order to most effectively provide comprehensive care for youth with epilepsy.


[Experiences of older multimorbid persons during the COVID-19 pandemic: a qualitative study].
The COVID-19 pandemic and the accompanying preventive measures have shaped social life in unexpected ways. Because older persons with multiple chronic conditions have a high risk of a severe medical outcome, it has been strongly recommended that social contacts be curtailed in order to minimize risks of infection. While this appears to be alarming from a psychosocial point of view, it has been shown that older persons exhibit a high degree of equanimity and a good ability to cope with the crisis. The aim of the study was to describe the attitudes of multimorbid older people to the pandemic, their social contacts and their experiences with medical care. This cross-sectional qualitative survey was based on 21 semi-structured short interviews of older patients with multiple chronic conditions during inpatient health care, at 4 different points in time: July 2020, September 2020, November 2020 and January 2021. The data were analyzed by qualitative content analysis. The statements of 21 participants (aged 58-88 years) were assessed. Over the course of the COVID-19 pandemic it became apparent that participants experienced the pandemic differently, both from an individual perspective and over time. While high infection rates were accompanied by serious concerns about health, periods of moderate infection risk were dominated by worry about social changes. In older persons there was a great sense of acceptance of the preventive measures. Our study exemplarily illustrates the attitudes and concerns of older persons who suffer from multiple chronic conditions over the course of the pandemic. Our data show that older persons reacted with equanimity to the novel medical and social circumstances.


The Sturgeon Vas Cautery: the first 600 cases.
The Sturgeon Vas Cautery, an inexpensive, reusable battery-powered modular unit, has been used in 600 consecutive successful vasectomies with a minimum of complications and without equipment breakdown.


Gardenia extract protects against intrahepatic cholestasis by regulating bile acid enterohepatic circulation.
Cholestasis is the main manifestation of cholestatic liver disease, which has a risk of progression to end-stage liver disease. Gardeniae Fructus is the dried fruit of Gardeniae jasminoides Ellis, a plant of the Rubiaceae family. Gardeniae Fructus has shown therapeutic potential in cholestasis-related liver diseases and it is generally believed that Gardeniae Fructus ameliorates cholestasis, which could be related to its influence on bile acids (BAs) metabolism. However, the specific targets of Gardeniae Fructus and its impact on enterohepatic circulation of BAs have not yet been fully elucidated. To systematically elucidate the mechanism by which Gardenia extract (GE, total iridoids in Gardeniae Fructus, which contains the predominant and characteristic phytoconstituents of Gardeniae Fructus) ameliorates alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Sprague-Dawley rats were orally administered water, obeticholic acid (OCA, 2 mg/kg), or GE (21 and 42 mg/kg) once daily for five days. On the third day, the model was established by administration of a single dose of ANIT (40 mg/kg) by oral gavage. Biochemical and pathological analyses, BA metabolomics, transcriptomics, and qRT-PCR were performed. The profile of BAs in serum and liver confirmed that GE attenuated ANIT-induced acute cholestasis by affecting BA metabolism in a dose-dependent manner. Liver transcriptomic analysis indicated that GE mainly influenced the primary bile acid (PBA) biosynthesis and bile secretion pathways. GE mainly affected PBA biosynthesis in liver by upregulating Cyp8b1 gene expression, thereby significantly reducing the level of total bile acids (TBA). GE mainly promoted PBA excretion from liver into duodenum by upregulating Fxr and Oatp1 gene expression, thereby increasing the excretion of PBA in feces, and inhibiting PBA in liver entering the blood by alternative routes to reduce TBA levels in serum and urine and improve the enterohepatic circulation of BAs. GE attenuated ANIT-induced hepatotoxicity and cholestasis in rats by upregulating Cyp8b1 expression to inhibit BA synthesis in the liver, while also promoting BA excretion via the intestinal-fecal route, and improving enterohepatic circulation of BAs.


Physico-chemical characteristics and correlation, and regression study on ground water of Coimbatore north zone.
Ground water samples were collected from 18 wards of Coimbatore City north zone, among which 2 samples were collected from 2 different locations from each ward, total 36 samples: Water quality assessment was carried out for the parameters like temperature, odour, taste, colour, turbidity, pH, electrical conductivity, total dissolved solids, chlorides, hardness, alkalinity, calcium, sodium and potassium. Correlation coefficients were determined to identify the highly correlated and interrelated water quality parameters. Regression equations relating these identified correlated parameters were formulated. Comparison of observed and estimated values of the different parameters reveals that the regression equations developed in the study can be very well used for making water quality monitoring by observing the above said parameters alone. This provides an easy and rapid method of monitoring of water quality.


Early life microbial exposures shape the Crassostrea gigas immune system for lifelong and intergenerational disease protection.
The interaction of organisms with their surrounding microbial communities influences many biological processes, a notable example of which is the shaping of the immune system in early life. In the Pacific oyster, Crassostrea gigas, the role of the environmental microbial community on immune system maturation - and, importantly, protection from infectious disease - is still an open question. Here, we demonstrate that early life microbial exposure durably improves oyster survival when challenged with the pathogen causing Pacific oyster mortality syndrome (POMS), both in the exposed generation and in the subsequent one. Combining microbiota, transcriptomic, genetic, and epigenetic analyses, we show that the microbial exposure induced changes in epigenetic marks and a reprogramming of immune gene expression leading to long-term and intergenerational immune protection against POMS. We anticipate that this protection likely extends to additional pathogens and may prove to be an important new strategy for safeguarding oyster aquaculture efforts from infectious disease. tag the videobyte/videoabstract in this section Video Abstract.


Recycling sludge-derived hydrochar to facilitate advanced denitrification of secondary effluent: Role of extracellular electron transfer.
Sludge-derived hydrochar (SDHC) was recycled to enhance the denitrification of secondary effluent. Under different carbon to nitrogen (C/N) ratios, the nitrogen removal efficiency (NRE) and carbon source efficiency (CSE) of denitrification coupled with SDHC (DN-SDHC) were distinctly higher than that of denitrification alone (DN). Moreover, at the C/N ratios of 3.0-3.2 and 5.8-5.9, the nitrogen removal rate (NRR) of DN-SDHC was 3.6- and 1.5-fold that of DN, respectively. The characterization of SDHC before and after used in denitrification indicated that the metal ions and functional groups did not participate in denitrification. Although SDHC has no redox capacity to donate electron for denitrification, its higher conductivity enabled the acceleration of extracellular electron transfer from carbon source to denitrifiers. The abundance of denitrifying community and functional genes was synchronously promoted by SDHC. Especially, the significant increase of nosZ gene encoding nitrous oxide reductase was conducive to mitigating the emission of N2O greenhouse gas.


[Mutation and expression of nm23-H1 and CD44 gene in prostate cancers].
To study the role of nm23-H1 and CD44 gene in carcinogenesis and metastasis of prostate cancers. Expression of nm23-H1/NDPK and CD44 protein were analyzed in 32 cases of prostate cancers (Pca) and 12 control of benign prostate hyperplasia (BPH) paraffin embedded tissue by immunohistochemistry. Mutation and expression of their genes were detected by silver SSCP method, semiquantitative RT-PCR, and southern blot hybridization analysis respectively in 25 cases of fresh Pca and 15 control BPH tissue. nm23-H1 gene point mutation was detected in 13.3% (2/15) of Pca. Compared with the control tissue, the expression of nm23-H1 gene was increased significantly on both mRNA and protein levels in the carcinoma tissue (P < 0.05). The expression of nm23-H1 protein was also increased significantly in Pca with metastasis. The expression of CD44 standard form (CD44s) protein was significantly reduced in most Pca compared with BPH tissue. CD44s mRNA was detected in all Pca and BPH tissue, whereas CD44 variant (CD44v) without CD44v6 was mainly detected in carcinoma tissue. The altered expression of CD44s and CD44v may co-regulate in the carcinogenesis and progression, whereas nm23-H1 gene may play a different role from CD44 in the progression of prostate cancer. CD44v6 may be a useful but not significant tool for detection of colon or bladder cancers.


Nuclear trafficking and export of single, native mRNPs in Chironomus tentans salivary gland cells.
Real-time observation of single molecules or biological nanoparticles with high spatial resolution in living cells provides detailed insights into the dynamics of cellular processes. The salivary gland cells of Chironomus tentans are a well-established model system to study the processing of RNA and the formation and fate of messenger ribonucleoprotein particles (mRNPs). For a long time, challenging imaging conditions limited the access to this system for in vivo fluorescence microscopy. Recent technical and methodical advantages now allow observing even single molecules in these cells. We describe here the experimental approach and the optical techniques required to analyze intranuclear trafficking and export of single native mRNPs across the nuclear envelope.


Bartonellosis in Dogs and Cats, an Update.
The unique virulence factors of Bartonella spp make them stealth pathogens that evade the immune system and cause persistent infections that are often difficult to diagnose and treat. Understanding these pathogenic mechanisms allows clinicians to recognize when to pursue diagnostics, how to optimize diagnostic testing and treatment, and ultimately can lead to improved outcomes.


Conservation of folding pathways in evolutionarily distant globin sequences.
To test the hypothesis that the folding pathways of evolutionarily related proteins with similar three-dimensional structures but widely different sequences should be similar, the folding pathway of apoleghemoglobin has been characterized using stopped-flow circular dichroism, heteronuclear NMR pulse labeling techniques and mass spectrometry. The pathway of folding was found to differ significantly from that of a protein of the same family, apomyoglobin, although both proteins appear to fold through helical burst phase intermediates. For leghemoglobin, the burst phase intermediate exhibits stable helical structure in the G and H helices, together with a small region in the center of the E helix. The A and B helices are not stabilized until later stages of the folding process. The structure of the burst phase folding intermediate thus differs from that of apomyoglobin, in which stable helical structure is formed in the A, B, G and H helix regions.


Nutritional support for the shock patient.
In the past, patients were indescriminately fed until they began to gain weight; however, this should not be the philosophy today. With the specialized solutions and laboratory tests available today, precise tailoring of a patient's nutritional needs can be achieved. Nutritional support has been devised to maintain the energy, vitamins, and minerals necessary to supply amino acids for protein synthesis and to reduce the loss of amino acids from the periphery. Providing patients with early nutritional supplementation either by the parenteral or enteral route decreases the incidence of septic complications by improving overall nutritional status and maintaining immune competence and wound healing. Careful determination of the patient's nutritional needs and close monitoring during therapy are important nursing interventions. As the patient recovers from the shock state, the catabolic phase gradually gives way to an anabolic phase. There is a decrease in urinary nitrogen excretion that reflects a decrease in protein catabolism. The stress hormones of catabolism change to the growth hormones of anabolism. The state of convalescence can continue for weeks to months depending on the body protein and fat lost during the stressed state. As the nurse prepares to administer enteral or parenteral nutrition, a thorough assessment is obtained, including history of current illness, recent weight changes, and food allergies or intolerances. Solutions are administered according to institutional policies. Patients are evaluated to ensure that nutritional support is effective. Visceral protein status and fluid and electrolyte balances should improve. Nutritional support is not static, but requires ongoing assessment and reevaluation. The route, composition, and quantity of the formula are adjusted to meet the changing requirements of the patient.


The Impact of Radiation Therapy, Lymph Node Dissection, and Hormonal Therapy on Outcomes of Tissue Expander-Implant Exchange in Prosthetic Breast Reconstruction.
Total skin-sparing mastectomy, with preservation of the nipple-areola complex, must account for adjuvant medical and surgical treatments for cancer. The authors assessed risk factors for complications after second-stage tissue expander-implant exchange. The authors reviewed all institutional total skin-sparing mastectomy cases that had completed tissue expander-implant exchange with at least 3 months of follow-up. They developed multivariate generalized estimating equation models to obtain adjusted relative risks of radiation therapy, type of lymph node dissection, and hormonal therapy in relation to postoperative complications. The authors performed 776 cases in 489 patients, with a median follow-up of 26 months (interquartile range, 10 to 48 months). Radiation therapy was associated with increased wound breakdown risk [relative risk (RR), 3.3; 95 percent CI, 2.0 to 5.7]; infections requiring oral antibiotics (RR, 2.2; 95 percent CI, 1.31 to 3.6), intravenous antibiotics (RR, 6.4; 95 percent CI, 3.9 to 10.7), or procedures (RR, 8.9; 95 percent CI, 4.5 to 17.5); implant exposure (RR, 3.9; 95 percent CI, 1.86 to 8.3); and implant loss (RR, 4.2; 95 percent CI, 2.4 to 7.4). Axillary lymph node dissection was associated with an increased risk of implant loss (RR, 2.0; 95 percent CI, 1.11 to 3.7) relative to sentinel lymph node biopsy. Axillary lymph node dissection increases the risk of implant loss compared with sentinel lymph node biopsy, independent of radiation therapy. Patients who require axillary lymph node dissection may be encouraged to undergo breast conservation or autologous reconstruction when possible. Therapeutic, III.


Using recombinant camel chymosin to make white soft cheese from camel milk.
Bovine derived chymosin in rennet cannot coagulate camel milk (CAM). The study aimed at producing cheese curd from CAM using a recombinant camel chymosin. Pasteurized CAM was prepared for curdling using a recombinant camel chymosin (50 IMCU/ kg). CAM (pH 6.65) contained 2.83% Fat, 3.34% proteins and 9.11% non-fat solids. Physicochemical properties of soft cheese from cultured CAM were 51.89%, 15.62%, 20.21% and 2.47% for moisture, protein, fat and ash, respectively. Cultured CAM afforded higher cheese yield (8.75%) than non-cultured CAM (3.34%). CAM cheese whey had 48.94% and 76.80% of the fat and proteins, respectively, of their corresponding concentrations in CAM. The study is the first report on soft cheeses from CAM (cultured and non-cultured) using a recombinant camel chymosin, with reference to whey constituents. CAM cheese and whey could be added-value products.


Temperature problems in the postoperative period.
Postoperative patients have difficulty maintaining thermal balance for several reasons. Normal thermoregulation is suppressed by anesthesia, neuromuscular blocking agents, and other drugs, and cool environmental conditions and exposure contribute to heat loss. Specific patient groups at high risk for hypothermia include infants, the elderly, and the neurologically impaired. Temperature drift, afterfall, shivering, malignant hyperthermia, and fever are among the temperature-related conditions requiring vigilant assessment and nursing action during the postoperative period.


Oxygenation of mitochondrial membranes by the erythroid lipoxygenase. Consequences for membrane properties.
The reticulocyte lipoxygenase is able to oxygenate mitochondrial membranes. The main products formed during this reaction are 15S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE) and 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13-HODE). The oxygenation of mitochondrial membranes is accompanied by an inactivation of enzymes localized in the outer and inner mitochondrial membranes, by a drastic change of the passive electric properties and by a destruction of the iron-sulfur clusters of the outer mitochondrial membrane. The possible mechanism of the processes leading to these functional changes is discussed.


Cranial anatomy and implications of Dolichocebus, a late Oligocene ceboid primate.
THE very scarce fossil record of Cainozoic New World monkeys(1,2) has contributed little to knowledge of the history of platyrrhine primates, an important element of both the neotropical mammal fauna(3) and the pantropical primates, as a whole. Only the affinities of the Middle Miocene Colombian fossils Neosaimiri, Stirtonia and Cebupithecia seem reasonably well established(4), though not without dissent(5), and these are clearly linked with the modern squirrel, howler and sakiuakari monkeys, respectively. After completion of a survey of the morphology and interrelationships of the platyrrhines, to be detailed elsewhere (A. L. R., in preparation), it is now possible to discuss the evolutionary implications of the terminal Oligocene Dolichocebus gaimanesis of Patagonia, represented by a nearly complete cranium only recently prepared fully, although first described in 1942 (ref. 6). This specimen strongly suggests that Dolichocebus is a member of the Saimiri lineage, which thus becomes the oldest generic lineage known for the primates, dating from about 25 Myr ago(7). Its affinities also imply that the two major monophyletic divisions of Ceboidea were already established by late Oligocene times, as were the marmosets and tamarins.


Impact of experimental obesity on diaphragm structure, function, and bioenergetics.
Obesity is associated with bioenergetic dysfunction of peripheral muscles; however, little is known regarding the impact of obesity on the diaphragm. We hypothesized that obesity would be associated with diaphragm dysfunction attributable to mitochondrial oxygen consumption and structural and ultrastructural changes. Wistar rat litters were culled to 3 pups to induce early postnatal overfeeding and consequent obesity. Control animals were obtained from unculled litters. From postnatal day 150, diaphragm ultrasound, computed tomography, high-resolution respirometry, immunohistochemical, biomolecular, and ultrastructural histological analyses were performed. The diaphragms of obese animals, compared with those of controls, presented changes in morphology as increased thickening fraction, diaphragm excursion, and diaphragm dome height, as well as increased mitochondrial respiratory capacity coupled to ATP synthesis and maximal respiratory capacity. Fatty acid synthase gene expression was also higher in obese animals, suggesting a source of energy for the respiratory chain. Myosin heavy chain-IIA was increased, indicating shift from glycolytic toward oxidative muscle fiber profile. Diaphragm tissue also exhibited ultrastructural changes, such as compact, round, and swollen mitochondria with fainter cristae and more lysosomal bodies. Dynamin-1 expression in the diaphragm was reduced in obese rats, suggesting decreased mitochondrial fission. Furthermore, gene expressions of peroxisome γ proliferator-activated receptor coactivator-1α and superoxide dismutase-2 were lower in obese animals than in controls, which may indicate a predisposition to oxidative injury. In conclusion, in the obesity model used herein, muscle fiber phenotype was altered in a manner likely associated with increased mitochondrial respiratory capability, suggesting respiratory adaptation to increased metabolic demand.NEW & NOTEWORTHY Obesity has been associated with peripheral muscle dysfunction; however, little is known about its impact on the diaphragm. In the current study, we found high oxygen consumption in diaphragm tissue and changes in muscle fiber phenotypes toward a more oxidative profile in experimental obesity.


Menopause in Morocco: symptomatology and medical management.
To assess the frequency of menopausal symptoms and patterns of recourse to medical care in Rabat, Morocco. Face to face interviews with a representative sample of 300 women aged 45-55 years; information was collected on socio-demographic variables, reproductive history, use of health care, symptom checklist, and medical management of menopause. The most frequent complaints are fatigue and hot flashes, each reported by 61% of women, headaches (57%), joint pain (54%), anxiety (44%) and irritability (42%). Hot flashes, but not cardiovascular symptoms, are statistically associated with menopausal status. Only 5% of women in the sample take hormones, and 4% calcium; 13% continue to take contraceptives. The frequency of some symptoms and the use of health care for menopause are influenced by socio-economic factors. Reports of hot flashes and joint pains are relatively high, but the frequency of use of medical services for menopause is low.


[Clinical practice of spherical allogeneic biological membranous implant in the eye socket].
To investigate the effect of implantation of spherical allogeneic biological material implant after eyeball enucleation. A spherical allogeneic biological material implant was implanted in the eye socket after eyeball enucleation in 50 cases including stage I in 48 cases and stage II in 2 cases. After operation, the motility of installed artificial eyes was good in 49 cases, the orbit and eyelids were full in all the cases. In the follow-up of 4 - 24 months (mean, 8 months), the conjunctival wound and muscular tissue were adherent firmly to the biological material, and there were no postoperative infection, no dislocation and shift of the implant. The spherical allogeneic biological membranous implant is an ideal material for the implantation in the eye socket after enucleation.


Quantification of expression and methylation of the Igf2r imprinted gene in segmental trisomic mouse model.
Insulin-like growth factor 2 receptor (Igf2r), a maternally expressed imprinted gene, is triplicated in Ts43H trisomic mice. To verify its expression in a trisomic mode, we examined the allele-specific transcripts and relative levels of Igf2r mRNA in trisomic and control mice. Igf2r was expressed from the maternal allele(s) and silenced on the paternal allele(s) in most tissues of maternally or paternally derived Ts43H mice. The triallelic expression was observed in adult brain and testis and in embryonic head, but the antisense transcript, Air, was strictly paternal, and methylation of region 2 was strictly maternal in all tissues. The Igf2r expression in maternally derived trisomics, with two active copies of the gene, did not exceed the average mRNA levels of euploid controls with monoallelic expression. Thus, an indication is presented for a dosage compensation mechanism of Igf2r in the trisomic context.


Evaluation of a flavonoid library for inhibition of interaction of HIV-1 integrase with human LEDGF/p75 towards a structure-activity relationship.
Background: Proteinśprotein interaction (PPI) between lens epithelium-derived growth factor (LEDGF/p75) and human immunodeficiency virus (HIV) integrase (IN) becomes an attractive target for anti-HIV drug development.Methods: The blockade of this interaction by small molecules could potentially inhibit HIV-1 replication. In this study, a panel of 99 structurally related flavonoids were was tested, concerning their ability to inhibit IN-LEDGF/p75 interaction, using a homogeneous time time-resolved fluorescence (HTRF) assay. Results: From the obtained results, it was possible to observe that the flavonoid with hydroxyl group in C3-, C4-, C5- and C7-position on the A-ring, C4'- and C5'-position of the B-ring, a carbonyl group of the C-ring, was more active against IN-LEDGF/p75 interaction, through competitive inhibition. Moreover, the binding modes of representative compounds, including myricetin, luteolin, dihydrorobinetin, naringenin, epicatechin, genistein and helichrysetin, were analyzedanalysed by molecular docking. Biolayer interferometry assay confirmed that these representative compounds disrupted the PPI by binding to IN with KD values ranging from 1.0 to 3.6 µM.Conclusion: This study presents the first to quantitative comparation of the effect of flavonoids with different structural subclasses on IN-LEDGF/p75 interaction. Our findings provide new insights into the development of inhibitors targeting IN-LEDGF/p75 interaction using flavonoids. Key MessagesHIV-1 integrase (IN)-LEDGF/p75 interaction is an attractive target for antiviral drug development.For the first time, the structure-activity relationship of flavonoids belonging to seven flavonoidic subclasses on IN-LEDGF/p75 interaction was determined.This study comprehends an HTRF-based screening system, biolayer interferometry and an in silico molecular docking analysis.


Smoothness of the knee joint movement during the stance phase in patients with severe knee osteoarthritis.
Patients with knee osteoarthritis can significantly affect the function of the knee joint in terms of joint range and mobility and have a stereotypical pattern of knee stiffness during gait, caused by an increased resistance in the muscles and soft tissues during the stance phase of knee joint movement. Smoothness in movement, such as during walking and running, is assumed to be attained by adulthood; however, disruptions in gait pattern due to injury or performance enhancement can alter the smoothness of the movement, and this is often quantified in terms of "jerk". A higher jerk value is linked with a decrease in smoothness. However few have reported to evaluate the smoothness of the knee joint movement during walking in patients with knee osteoarthritis. The purpose of the present study was to quantify the smoothness of the knee joint movement during walking in people with knee osteoarthritis. Patients were classified as having early or severe knee osteoarthritis. There were eight patients in each group (16 knees; three males, five females). The normalized angular jerk was calculated as an indicator of the walking knee joint smoothness in each of the four periods of the stance phase. Two-way ANOVA was performed to compare the smoothness of knee joint movement between groups and between each period of the stance phase. The angular change in the sagittal plane of those with severe knee osteoarthritis was smaller than that of those with early knee osteoarthritis in all periods of the stance phase. Normalized angular jerk did not significantly differ between groups in all periods. In both groups, the normalized angular jerk in the sagittal plane was significantly larger in the mid-stance and terminal stance periods than in the early stance and pre-swing periods. Only in patients with severe knee osteoarthritis, there was a significantly larger jerk in the frontal plane in the mid-stance period. The present results revealed that the smoothness of joint movement decreases during the single leg supporting phase of the stance phase in the frontal plane with severe knee osteoarthritis, although there is no difference in smoothness of joint movement according to the severity of knee osteoarthritis The instability during single leg support due to increase of the knee joint load and destruction cause the impaired smoothness of the knee joint movement.


Update on advances in upper extremity prosthetics.
Upper extremity amputations are common. Fortunately, most of these involve loss of only a finger or portion thereof. Hand and upper limb surgeons are best suited to lead the team and help these patients following these injuries. Proximal amputations can be devastating for the patient, but recent prosthetic advances have helped many patients lead a better life and, often, return to activities they were involved in before their amputation. The purpose of this article is to review the current prostheses available for upper extremity amputees.


Antibody-dependent cellular cytotoxicity to human colon-tumour cells. I. Lack of tumour specificity in a population study.
The humoral and cellular components of the antibody-dependent cellular cytotoxicity (ADCC) against allogeneic human colonic tumour cell lines were evaluated. The 2 colon cell lines used in this study (HT-29 and ACC-20) were found by immunofluorescence to have carcinoembryonic antigen (CEA) on their surface, and to become sensitive to the lytic effect of unstimulated lymphocytes after coating with heterologous anti-CEA. This reaction was used to evaluate the ADCC activity of mononuclear cells from the peripheral blood of patients with gastrointestinal cancer (mostly local extensive colo-rectal). Remarkable variability was found in the lytic capability (2-50% specific lysis) of both cancer and non-cancer mononuclear cells, with no significant difference between them. Sera from 127 cancer patients and 91 non-cancer patients were tested, using the reaction with heterologous anti-CEA as positive control and as a reference point. In 46 cases (21%) the sera were reactive in this system, and 43 of them were of Blood Group O. However, there was no difference between the cancer patients and the normal controls. The antigenic determinant involved in this reaction is not the Blood Group A specificity but, most probably, a polypeptide common to CEA and A (as shown in the following publication). In addition, trials for the elimination of the non-tumour-specific reaction, by absorption or inhibition, failed to disclose a tumour-specific one. The value of the ADCC assay in monitoring human tumour immunity, and possible ways of eliminating reactivity to normal antigens in this system, are discussed in the light of these findings.


Reduction of excess sludge production in sequencing batch reactor (SBR) by lysis-cryptic growth using homogenization disruption.
A lysis-cryptic growth system, which combined high-pressure-homogenization (HPH) for sludge disruption, was proposed to reduce excess sludge production in SBR. Experimental data was analyzed with the aid of response surface models to determine the optimal HPH disruption pressure, which was 70 MPa. By combining a 5.4 m3/d pilot SBR with HPH disruption, the new system achieved a 42.4% sludge reduction rate over a 75 days operation. Based on measurement of oxygen uptake rate and activity of the dehydrogenase, the lysis-cryptic growth system resulted in negligible change of the sludge activity. However, an increase of 0.04 mg/L of total-phosphorus (TP) and 2.40 mg/L suspended-solids (SS) was observed in the effluent due to the process of lysis-cryptic growth. Except for above listed points, the new system demonstrated improved sludge reduction performance while the direct cost of pilot SBR lysis-cryptic growth was only 0.177US dollar per kilogram (dry sludge) according to estimation.


Engineering Robust Production Microbes for Large-Scale Cultivation.
Systems biology and synthetic biology are increasingly used to examine and modulate complex biological systems. As such, many issues arising during scaling-up microbial production processes can be addressed using these approaches. We review differences between laboratory-scale cultures and larger-scale processes to provide a perspective on those strain characteristics that are especially important during scaling. Systems biology has been used to examine a range of microbial systems for their response in bioreactors to fluctuations in nutrients, dissolved gases, and other stresses. Synthetic biology has been used both to assess and modulate strain response, and to engineer strains to improve production. We discuss these approaches and tools in the context of their use in engineering robust microbes for applications in large-scale production.


A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release.
A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.


Identification and characterization of the gonadotropin-releasing hormone response elements in the mouse gonadotropin-releasing hormone receptor gene.
The response of the pituitary gonadotrope to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of GnRHR gene expression. Several hormones have been implicated in this regulation, most notably GnRH itself. Despite these observations and the central role that GnRH is known to play in reproductive development and function, the molecular mechanism(s) by which GnRH regulates transcription of the GnRHR gene has not been well elucidated. Previous studies in this laboratory have identified and partially characterized the promoter region of the mouse GnRHR gene and demonstrated that the regulatory elements for tissue-specific expression as well as for GnRH regulation are present within the 1.2-kilobase 5'-flanking sequence. By using deletion and mutational analysis as well as functional transfection studies in the murine gonadotrope-derived alphaT3-1 cell line, we have localized GnRH responsiveness of the mouse GnRHR gene to two DNA sequences at -276/-269 (designated Sequence Underlying Responsiveness to GnRH-2 (SURG-2), which contains the consensus sequence for the activating protein-1-binding site) and -292/-285 (a novel element designated SURG-1), and demonstrated that this response is mediated via protein kinase C. By using the electrophoretic mobility shift assay, we further demonstrate that a member(s) of the Fos/Jun heterodimer superfamily is responsible in part for the DNA-protein complexes formed on SURG-2, using alphaT3-1 nuclear extracts. These data define a bipartite GnRH response element in the mouse GnRHR 5'-flanking sequence and suggest that the activating protein-1 complex plays a central role in conferring GnRH responsiveness to the murine GnRHR gene.


Metabolism of [3-3H]oleanolic acid in the isolated Calendula officinalis leaf cells and transport of the synthesized glycosides to the cell wall and the extracellular space.
It has been shown for the first time that [3-3H]oleanolic acid glycosides formed in the cytosol of C. officinalis leaf cells are transported to the extracellular space in the form of pentaglucoside VI (44%), whereas glucuronides derived from [3-3H]oleanolic acid 3-O-monoglucuronide (29%) as well as a part of glucosides (24%) were transported into the cell walls.


Epistasis, complex traits, and mapping genes.
Using a three-locus model wherein two loci regulate a third, candidate locus, I examine physiological epistasis from the 'gene's eye view' of the regulated locus. I show that, depending upon genetic background at the regulatory loci, an allele at the candidate locus can be dominant, additive, recessive, neutral, over-dominant, or under-dominant in its effects on fitness. This kind of variation in allelic effect caused by variation in genetic background from population to population, from time to time in the same population, or sample to sample makes finding and mapping the genes underlying a complex phenotype difficult. The rate of evolution of such genes can also be slowed, especially in genetically subdivided metapopulations with migration. Nevertheless, understanding how variation in genetic background causes variation in allelic effects permits the genetic architecture of such complex traits to be dissected into the interacting component genes. While some backgrounds diminish allelic effects and make finding and mapping genes difficult, other backgrounds enhance allelic effects and facilitate gene mapping.


Patterned enteroscopy balloon design factors influence tissue anchoring.
Balloon-assisted enteroscopy procedures allow visualization and intervention in the small intestine. These balloons anchor an endoscope and/or overtube to the small intestine, allowing endoscopists to plicate the small intestine over the overtube. This procedure can extend examination deeper into the small intestine than the length of the endoscope would allow with direct examination. However, procedures are often prolonged or incomplete due to balloon slippage. Enteroscopy balloons are pressure-limited to ensure patient safety and thus, improving anchoring without increasing pressure is essential. Patterning balloon exteriors with discrete features may enhance anchoring at the tissue-balloon interface. Here, the pattern design space is explored to determine factors that influence tissue anchoring. The anchoring ability of smooth versus balloons with patterned features is investigated by experimentally measuring a peak force required to induce slippage of an inflated balloon inside ex-vivo porcine small intestine. Stiffer materials, low aspect-ratio features, and pattern area/location on the balloons significantly increase peak force compared to smooth silicone balloons. Smooth latex balloons, used for standard enteroscopy, have the lowest peak force. This work demonstrates both a method to pattern curved surfaces and that a balloon with patterned features improves anchoring against a deformable, lubricated tissue interface.


Murine retroviruses re-engineered for lineage tracing and expression of toxic genes in the developing chick embryo.
We describe two replication incompetent retroviral vectors that co-express green fluorescent protein (GFP) and beta-galactosidase. These vectors incorporate either the avian reticuloendotheliosis (spleen necrosis virus; SNV) promoter or the chick beta-actin promoter, into the backbone of the murine leukemia (MLV) viral vector. The additional promoters drive transgene expression in avian tissue. The remainder of the vector is MLV-like, allowing high titer viral particle production by means of transient transfection. The SNV promoter produces high and early expression of introduced genes, enabling detection of the single copy integrated GFP gene in infected cells and their progeny in vivo. Substitution of the LacZ coding DNA with a relevant gene of interest will enable its co-expression with GFP, thus allowing visualization of the effect of specific and stable changes in gene expression throughout development. As the VSV-G pseudotyped viral vector is replication incompetent, changes in gene expression can be controlled temporally, by altering the timing of introduction.


Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma. Treatment of stage II melanoma with viral lysates.
A total of 80 patients with melanoma metastases in regional lymph nodes were treated by i.d. injections with a vaccine prepared from a vaccinia virus-infected allogeneic melanoma cell line; 39 patients have been followed for a 2-year period. Interim results from comparison of the treated group with 151 historical controls treated without the vaccine from September 1978 to December 1981 at the same institution and 56 non-randomized concurrent controls suggest that survival was significantly prolonged in the vaccinated group. At the 2-year period overall survival was 75% in the treated compared to 57% in the historical control group. Subset analysis showed a greater apparent benefit of vaccine therapy among patients who had metastases detected at the time of treatment of the primary melanoma (synchronous metastases), while therapy appeared less effective in patients with metastases detected at some time after treatment of the primary (delayed metastases). In the latter only those with one lymph node appeared to benefit from the treatment whereas in patients with synchronous metastases patients with three or more nodes as well as one node appeared to have improved survival. The survival rates at 2 years for treated patients with synchronous metastases in one, two, three or more lymph nodes was 100%, 83% and 79% respectively compared with that of 82%, 86% and 47% respectively in the equivalent control groups. Survival rates in treated patients with delayed metastases in one, two, three or more lymph nodes was 70%, 70% and 65% compared with 47%, 42% and 35% in the equivalent control groups. Treatment and control groups appeared well matched for a number of known prognostic features, including number and size of involved nodes, sex and thickness of primary tumor. Multivariate analysis indicated the effect of treatment was independent of these factors. Despite the empiricism of this approach the present results suggest that this form of therapy warrants further evaluation in a randomized controlled trial.


Substituent effects on "hyperconjugative" aromaticity and antiaromaticity in planar cyclopolyenes.
Computed aromatic stabilization energies (ASEs) and dissected nucleus independent chemical shifts (NICSπzz) quantify the effect of hyperconjugation on the (anti)aromaticities of the planar conformations of three, five, seven, and nine membered (CnHn)CR2 (R = H, SiH3, F) rings. CH2 and especially C(SiH3)2 groups supply two "pseudo" π electrons hyperconjugatively along with the olefinic π electrons in the ring, whereas a CF2 group acts like a partially vacant p orbital. Following the Hückel rule, compounds with 4n+2 (or 4n) pseudo π electrons are "hyperconjugatively" aromatic (or antiaromatic).


[Effects of different types of newborn infant feeding on intestinal microbiocenosis].
From 70 to 90% of premature infants on breast and additional feeding with a mixture of the "Similak" type showed normal bifidoflora, the main component of biocenosis of infant intestines. No positive shifts in the intestinal microflora composition or recovery of the bifidoflora physiological for children were recorded during feeding premature infants with pasteurized donor milk and additional feeding with kefir, a mixture of "Malyutka" and dry acidophilus mixture "Malyutka". Positive results of using the above food in conjunction with bifidumbacterin point to the perspectiveness of using bifidobacteria in the development of therapeutic additives to the infant diet.


Near Infra-Red Technology to Evaluate Segment IV in Split Liver Transplantation.
Indocyanine green injected intravenously has been employed in many fields of hepatobiliary surgery such as liver and biliary tree mapping, tumor detection, and graft evaluation in liver transplant. This latter application has, in our opinion, particular potentials when a split liver transplantation is performed 1-3. In this study, we used infrared technology to evaluate in real-time the segment 4 region in a recipient of extended right lobe transplantation. Donor data: 50 years old male, brain death, height, 1.70 mt, weight 69 kg; surgical technique employed was in situ standard split liver procurement. Recipient data: 46 years old male, height 1.75 mt; weight 67 k 23 g, affected by cirrhosis secondary HCV infection, with MELD Na 33. Standard orthotopic liver transplantation was performed with indocyanine green intravenous injection at 15 min after arterial reperfusion. Infrared technology, showed in this video, demonstrates progressive improvement of segment IV viability which was confirmed by the post-operative contrast-enhanced CT scan performed before discharge. The transplant procedure was uneventful and the patient discharged to home 10 days after surgery. The case reported in this video is, to the best of our knowledge, the first in the English literature showing how near infrared technology has predictive value on the evaluation of a split graft. Fast diffusion of the colorant allows dynamic early evaluation and may confirm the presence of intra-hepatic venous shunt, which will determine a full recovery of the originally ischemic area. On the contrary, a permanent absence of the staining might be predictive of dysfunction.


Do patients with bipolar disorder drink alcohol for different reasons when depressed, manic or euthymic?
Many studies report high prevalence rates for co-morbid alcohol problems in bipolar disorder (BP). Some hypothesize that individuals use alcohol to self-medicate, but few studies examine the range of possible reasons and none explicitly explores the role of mood state. We examined drinking motives in BP depression, (hypo)mania and euthymia according to Cooper's cognitive motivational model of alcohol use (Cooper, 1994). Twenty-seven participants with BP were interviewed using the Drinking Motives Questionnaire. A calendar-based measure of alcohol use--the FORM90--was used to aid recall of drink-related behaviours and estimate alcohol intake. Each participant reported drinking motives and alcohol consumption for 30 consecutive days of euthymia, plus one past depressive and one past (hypo)manic episode. Estimated alcohol intake was higher when depressed or (hypo)manic compared with euthymia. Drinking motives varied between mood states. Negative internal coping motives were specifically related to depression, whilst positive internal and external motives were more specifically related to (hypo)mania. During euthymia, the patients' motives did not differ from norms. This is the first clinical study utilising a clearly defined cognitive motivational model demonstrating that the reasons to drink alcohol in patients with BP are mood-dependent. Interventions aimed at modifying problematic drinking behaviours in this population must take into account both individual and mood state variations in reasons for alcohol consumption. Self-medication or inadequate coping is not sufficient to generally explain alcohol intake across mood states and individuals.


Immunohistological study for estrogenic activities of nitrophenols in diesel exhaust particles.
We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators and xenoestrogens. The estrogenic activity of PNMC and PNMPP was further examined by using immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in uterine luminal epithelium of ovariectomized 25-d-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 d. Significant increases were observed in uterine luminal epithelium in PCNA positive cells of animals receiving 10 and 100 mg/kg PNMC and 0.1 mg/kg PNMPP compared with controls. These results clearly show the estrogenic activity of PNMC and PNMPP by cell proliferation on the uterine luminal epithelium.


Scaffold devices for rotator cuff repair.
Rotator cuff tears affect 40% or more of those aged older than 60 years, and repair failure rates of 20% to 70% remain a significant clinical challenge. Hence, there is a need for repair strategies that can augment the repair by mechanically reinforcing it, while at the same time biologically enhancing the intrinsic healing potential of the tendon. Tissue engineering strategies to improve rotator cuff repair healing include the use of scaffolds, growth factors, and cell seeding, or a combination of these approaches. Currently, scaffolds derived from mammalian extracellular matrix, synthetic polymers, and a combination thereof, have been cleared by the U.S. Food and Drug Administration and are marketed as medical devices for rotator cuff repair in humans. Despite the growing clinical use of scaffold devices for rotator cuff repair, there are numerous questions related to their indication, surgical application, safety, mechanism of action, and efficacy that remain to be clarified or addressed. This article reviews the current basic science and clinical understanding of commercially available synthetic and extracellular matrix scaffolds for rotator cuff repair. Our review will emphasize the host response and scaffold remodeling, mechanical and suture-retention properties, and preclinical and clinical studies on the use of these scaffolds for rotator cuff repair. We will discuss the implications of these data on the future directions for use of these scaffolds in tendon repair procedures.


A review of opioid prescription in a teaching hospital in Colombia.
Review of opioid prescriptions in a hospital provides valuable information to health care professionals which may contribute to proper pain management; opioid utilization studies may help uncover factors that can be improved for better prescribing. To evaluate the use of opioid analgesics in a university hospital, a review of opioids prescribed in hospitalized patients was developed. Information was obtained from the pharmacy database and medical records. The study period was 1 month. Medical records of 1156 patients admitted in July 2009 were analyzed. The most widely prescribed opioid was tramadol; the preferred administration route was intravenous; the main indication was severe pain; and major prescribers were from surgical departments. Underutilization of potent opioids for acute and chronic pain seems to occur. Most prescribers prefer weak opioids, given intravenously to treat acute and chronic pain, while some patients may benefit from the prescription of more potent opioids.


LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies.
LIMK2, a serine-specific kinase, was discovered as an actin dynamics regulating kinase. Emerging studies have shown its pivotal role in numerous human malignancies and neurodevelopmental disorder. Inducible knockdown of LIMK2 fully reverses tumorigenesis, underscoring its potential as a clinical target. However, the molecular mechanisms leading to its upregulation and its deregulated activity in various diseases largely remain unknown. Similarly, LIMK2's peptide substrate specificity has not been analyzed. This is particularly important for LIMK2, a kinase almost three decades old, as only a handful of its substrates are known to date. As a result, most of LIMK2's physiological and pathological roles have been assigned to its regulation of actin dynamics via cofilin. This review focuses on LIMK2's unique catalytic mechanism, substrate specificity and its upstream regulators at transcriptional, post-transcriptional and post-translational stages. Moreover, emerging studies have unveiled a few tumor suppressors and oncogenes as LIMK2's direct substrates, which in turn have uncovered novel molecular mechanisms by which it plays pleiotropic roles in human physiology and pathologies independent of actin dynamics.