[The influence of electroacupuncture with different frequencies on the discharges of neurons in rostral ventromedial medulla on rats].
The experiments were carried out on rats, anesthetized with urethan and paralyed with tubocuraine. Stainless steel needles were inserted into bilateral "Zusanli" points. The unit discharges of RVM neurons were recorded extracellalarly by microelectrode. The searching of nociceptive neurons and processing of data were operated automatically by a real time control system. The results were as follow: 1. The pain response of excitatory neurons could be inhibited by 2 Hz EA (n = 15/22, P < 0.01), the mean inhibition rate was 32.40%. 2. The inhibitory effects of 2 Hz were completely blocked by naloxone pretreated (n = 5/5, P < 0.01). 3. The pain response of excitatory neurons could be inhibited by 10 Hz EA(n = 10/13, P < 0.01), the mean inhibition rate was 49.06%. 4. The inhibitory effects of 10 Hz EA were partially blocked by naloxone pretreated (n = 5/5, P < 0.01). 5. Both 2 Hz and 10 Hz EA could enhance the spontaneous discharges of excitatory neurons in RVM, and the percentage of change in the frequency was 62.45% and 112.02% respectively. 6. Neither 2 Hz nor 10 Hz EA could obviously influence the spontaneous activity of inhibitory neurons in RVM. The results suggest that both 2 Hz and 10 Hz EA could activate excitatory neurons in RVM, which may suppress nociceptive transmission via opioid mechanism.


Comparison of the structure and stability of new α-diimine complexes of copper(I) and silver(I): density functional theory versus experimental.
New compounds of the general formulas [M(Ar-BIAN)(2)]BF(4) and [M(Ar-BIAN)(NCMe)(2)]BF(4), where M = Cu(I) or Ag(I) and Ar-BIAN = bis(aryl)acenaphthenequinonediimine, were synthesized by the direct reaction of [Cu(NCMe)(4)]BF(4) or [Ag(NCMe)(4)]BF(4) with the corresponding Ar-BIAN ligand in dried CH(2)Cl(2). The synthesized compounds are [M(o,o',p-Me(3)C(6)H(2)-BIAN)(2)]BF(4) where M = Cu(I) (1) and Ag(I) (2), [M(o,o'-iPr(2)C(6)H(3)-BIAN)(NCMe)(2)]BF(4) where M = Cu(I) (3) and Ag(I) (4), and [Ag(o,o'-iPr(2)C(6)H(3)-BIAN)(2)]BF(4) (5). The crystal structures of compounds 1-3 and 5 were solved by single-crystal X-ray diffraction. In all cases copper(I) or silver(I) are in a distorted tetrahedron that is constructed from the four nitrogen atoms of the two α-diimine ligands or, in 3, from one α-diimine ligand and two acetonitrile molecules. All compounds were characterized by elemental analyses, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, and IR, UV-vis, and (1)H NMR spectroscopy. The analysis of the molecular geometry and the energetic changes for the formation reactions of the complexes, in a CH(2)Cl(2) solution, were evaluated by density functional theory calculations and compared with the experimental results.


Cutaneous B-cell lymphoma with signet ring-cell morphology: a clinicopathologic and immunohistochemical study of three cases.
Three cases of primary cutaneous B-cell lymphoma with prominent signet ring-cell features are presented. The patients were three men between the ages of 37 years and 74 years (average, 55.5 years). Clinically, the three patients presented with multiple skin nodules. In one patient, the nodules had been present for approximately 5 weeks, although in the two other patients, the nodules were of unknown duration. The lesions were located in the upper extremities (forearm) and measured from 2 cm to 3 cm in diameter. No evidence of lymphadenopathy was observed in any of the patients. Surgical excision of the nodules was performed. Histologically, in two cases, the superficial and deep dermis was replaced by a diffuse cellular proliferation, and in one patient, the tumor cell population adopted a nodular pattern of growth involving adnexal structures and infiltrating the subcutaneous fat. In all cases, the tumors were composed of cells showing signet ring-cell features, with striking indentation of the nuclei toward the periphery of the cell. Immunohistochemical studies using antibodies for B-cell and T-cell markers (L-26 and UCHL) as well as antibodies for leukocyte common antigen, keratin, and kappa and lambda light chains were performed in all cases. The tumor cells showed a positive reaction for leukocyte common antigen, L-26, and lambda light chain restriction. Follow-up information was only available in one patient, who has remained alive and well 2 years after diagnosis without evidence of progression of the disease. The present cases highlight the importance of recognizing this unusual morphologic type of lymphoma so as to arrive at a correct diagnosis.


[The effect of electro-acupuncture on the adrenal gland of endotoxic shocked rats].
The quantitative histochemical changes of glycogen SDH in the adrenal gland of endotoxic-shocked rat induced by electro-acupuncture were observed in this paper. The result indicates that electro-acupuncture at "Ren Zhong" or "Zusali" of endotoxic shocked animal might improve the function of adrenal cortex and achieve recovery in certain extent.


The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.
The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T-cell activation. It contains a sterile-alpha motif (SAM) domain, 3 phosphotyrosine motifs, a proline-rich region, and a Src homology 2 domain. Whereas the other domains have been extensively studied, the role of the SAM domain in SLP-76 function is not known. To understand the function of this domain, we generated SLP-76 knockin mice with the SAM domain deleted. Analysis of these mice showed that thymocyte development was partially blocked at the double-positive to single-positive transition. Positive and negative thymic selection was also impaired. In addition, we analyzed T-cell receptor (TCR)-mediated signaling in T cells from these mutant mice. TCR-mediated inositol 1,4,5-triphosphate production, calcium flux, and extracellular signal-regulated kinase activation were decreased, leading to defective interleukin-2 production and proliferation. Moreover, despite normal association between Gads and SLP-76, TCR-mediated formation of SLP-76 microclusters was impaired by the deletion of the SAM domain. Altogether, our data demonstrated that the SAM domain is indispensable for optimal SLP-76 signaling.


The influence of previous low birth weight on birth weight, gestational age, and anthropometric measurements in the current pregnancy.
The effect of a previous low birth weight birth (less than 2750 g) was examined using a series of regression analyses. Effects on birth weight were partitioned into those associated with preterm delivery (128 g) and term delivery (178 g). Among term births, a mean difference of 107 g was associated with a previous birth of less than 2750 g, even after controlling for other risk factors including smoking, drug and alcohol use, maternal race, size, and hypertension. The pattern of measurements seen after a previous birth of less than 2750 g included significantly smaller head, chest, abdomen, arm, and thigh circumferences, but an insignificant impact on skinfold thicknesses and no significant effect on length measurements.


A hard act to swallow: modern management of eosinophilic oesophagitis.
Eosinophilic oesophagitis (EO) is now established as an important cause of oesophageal symptoms. It is presumed to result from eosinophilic activation to dietary antigens, which is limited to the oesophagus. Inflammatory strictures and secondary dysmotility are common and contribute to symptomatology. Current management involves food exclusion diets and swallowed topical steroid. Strictures may require endoscopic dilatation. Relapse is common but strategies for maintaining remission are not well described. Here we describe a patient with severe stricturing EO, whose symptoms were significantly exacerbated by secondary oesophageal spasm. His symptoms were refractory to dietary, endoscopic and medical therapy including parenteral corticosteroid but responded dramatically to diltiazem. Remission was eventually achieved and maintained with azathioprine, and he was able to discontinue the other therapies and relax his dietary restrictions. We discuss the evidence for dietetic, endoscopic and pharmacological interventions for this disease.


Ghrelin and functional dyspepsia.
The majority of patients with dyspepsia have no identifiable cause of their disease, leading to a diagnosis of functional dyspepsia (FD). While a number of different factors affect gut activity, components of the nervous and endocrine systems are essential for normal gut function. Communication between the brain and gut occurs via direct neural connections or endocrine signaling events. Ghrelin, a peptide produced by the stomach, affects gastric motility/emptying and secretion, suggesting it may play a pathophysiological role in FD. It is also possible that the functional abnormalities in FD may affect ghrelin production in the stomach. Plasma ghrelin levels are reported to be altered in FD, correlating with FD symptom score. Furthermore, some patients with FD suffer from anorexia with body-weight loss. As ghrelin increases gastric emptying and promotes feeding, ghrelin therapy may be a new approach to the treatment of FD.


Nephrogenic diabetes insipidus induced by two amphotericin B liposomal formulations.
Immunocompromised patients are at risk for invasive molds and resistant fungal infections for which amphotericin B may be the only feasible treatment. Nephrogenic diabetes insipidus (DI) and renal tubular acidosis are known adverse effects of conventional amphotericin B; however, nephrogenic DI has been uncommonly associated with liposomal amphotericin B formulations. We describe an 18-year-old woman with aplastic anemia who developed invasive aspergillosis. She began treatment with high-dose (10 mg/kg/day) liposomal amphotericin B at home; however, her condition worsened, and she was hospitalized. Therapy with liposomal amphotericin B was continued until the patient began having symptoms consistent with nephrogenic DI. These symptoms resolved after discontinuation of liposomal amphotericin B; however, after rechallenge with lipid complex amphotericin B (5 mg/kg/day), the symptoms returned. The patient's nephrogenic DI was successfully treated with diuretics. Use of the Naranjo adverse drug reaction probability scale score indicated a probable relationship between liposomal amphotericin B and the development of nephrogenic DI. To our knowledge, this is the third report of nephrogenic DI induced by liposomal amphotericin B. This adverse effect is one of many severe adverse effects caused by all formulations of amphotericin B. A clear understanding of these adverse effects is vital for the clinician to successfully weigh the risks and benefits of antifungal therapy.


The use of Markov chain Monte Carlo uncertainty analysis to support a Public Health Goal for perchloroethylene.
The current Public Health Goal (PHG) for perchloroethylene (PCE) was derived using upper-bound estimates of fractional PCE metabolism in humans. These estimates were in part obtained from a published evaluation of the uncertainty and variability in human PCE metabolism conducted using a physiologically-based pharmacokinetic (PBPK) model in a Markov chain Monte Carlo (MCMC) analysis; however, the data used in that analysis were limited to post-exposure PCE blood and exhaled air concentrations from a single study. A more recent study [Volkel, W., Friedewald, M., Lederer, E., Pahler, A., Parker, J., Dekant, W., 1998. Biotransformation of perchloroethene: dose-dependent excretion of trichloroacetic acid, dichloroacetic acid, and N-acetyl-S-(trichlorovinyl)-l-cysteine in rats and humans after inhalation. Toxicol. Appl. Pharmacol. 153(1), 20-27.] provides data on blood concentrations of PCE and its major metabolite, trichloroacetic acid (TCA), and urinary excretion of TCA following exposure of human subjects to lower concentrations of PCE (10-40ppm) than in previous studies. In the present effort, a new MCMC analysis was performed that focused on data from this study along with two others [Fernandez, J., Guberan, E., Caperos, J., 1976. Experimental human exposures to tetrachloroethylene vapor and elimination in breath after inhalation. Am. Ind. Hyg. Assoc. J. 37, 143-150; Monster, A., Boersma, G., Steenweg, H., 1979. Kinetics of tetrachloroethylene in volunteers; influence of exposure concentration and work load. Int. Arch. Occup. Environ. Health 42, 303-309.] providing data on PCE blood concentrations and urinary excretion of TCA. To provide an accurate prediction of TCA kinetics, the PBPK model used here includes a description of the metabolism of PCE to TCA in both the liver and kidney. The resulting upper 95th percentile estimates of fraction of PCE metabolized by inhalation and oral routes were 2.1 and 5.2%, respectively, compared to 58 and 79% used in the derivation of the PHG.


Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in vitro cyst growth of human ADPKD cyst epithelial cells.
In autosomal dominant polycystic kidney disease (ADPKD), aberrant proliferation of the renal epithelial cells is responsible for the formation of numerable fluid-filled cysts, massively enlarged kidneys, and progressive loss of renal function. cAMP agonists, including arginine vasopressin, accelerate cyst epithelial cell proliferation through protein kinase A activation of the B-Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway. The mitogenic effect of cAMP is equally potent and additive to growth factor stimulation. Here, we determined whether Sorafenib (BAY 43-9006), a small molecule Raf inhibitor, inhibits proliferation of cells derived from the cysts of human ADPKD kidneys. We found that nanomolar concentrations of Sorafenib reduced the basal activity of ERK, inhibited cAMP-dependent activation of B-Raf and MEK/ERK signaling, and caused a concentration-dependent inhibition of cell proliferation induced by cAMP, epidermal growth factor, or the combination of the two agonists. Sorafenib completely blocked in vitro cyst growth of human ADPKD cystic cells cultured within a three-dimensional collagen gel. These data demonstrate that cAMP-dependent proliferation of human ADPKD cyst epithelial cells is blocked by Sorafenib and suggest that small molecule B-Raf inhibitors may be a therapeutic option to reduce the mitogenic effects of cAMP on cyst expansion.


Clinicopathological features of severe and fulminant forms of autoimmune hepatitis.
Diagnosis of the acute presentation of autoimmune hepatitis (AIH) is difficult because patients do not always show typical clinicopathological features of AIH. Although some of them progress to fulminant hepatitis, the survival rate of which is <20% without liver transplantation, their clinicopathological features have remained uncertain. We examined them for a better understanding and improvement of the prognosis of "life-threatening" severe and fulminant AIH. Clinical, biochemical and pathological features of 28 patients with severe or fulminant AIH and treatment responses were examined retrospectively. At the time of admission, mean immunoglobulin G was 2479 ± 1170 mg/dl, with 7 (25%) patients showing normal levels. Anti-nuclear antibody was ≤ 1:40 in 8 (29%). Liver histology showed severe activity in 95% and acute hepatitis in 86% of the patients. Centrilobular necrosis including submassive and massive necrosis was characteristic. Of the 25 patients treated with corticosteroids, 17 responded and 8 did not. Responders to corticosteroids showed younger age and higher prothrombin time (PT) activity than non-responders at the time of corticosteroid administration. The improvement of PT activity during 2 weeks and 4 weeks and total bilirubin level during 4 weeks was statistically significant in responders, but not in non-responders. We should diagnose and treat acute onset AIH patients before they develop into severe and fulminant disease. Performing liver biopsy at the early stage of acute onset AIH, evaluating the biopsy specimens precisely and initiating corticosteroid therapy may be essential for improving the prognosis without liver transplantation.


Reaction to frustration in high and low feather pecking laying hens.
Reaction to frustration of high (HFP) and low feather pecking (LFP) laying hens was investigated. From a HFP- and a LFP-line five birds with a HFP- and five birds with a LFP-phenotype were selected. Birds from the HFP-line were expected to show more key pecking and covered feeder pecking during frustration than birds from the LFP-line. When a bunch of feathers was presented, birds with a HFP-phenotype were expected to redirect their pecks at the bunch. Birds were trained to peck a key for a food reward in an automated Skinnerbox and subjected to two sessions: a control session, where food was available, and a frustration session, where the feeder was covered with Perspex. These two sessions were repeated in the presence of a bunch of feathers. Unexpectedly, birds from the LFP-line had a stronger reaction to frustration than birds from the HFP-line, expressed in pecking behaviour. When a bunch of feathers was offered, birds with a HFP-phenotype did not show more bunch pecking during frustration than birds with a LFP-phenotype.


[Incidence of HPV and CIN in HIV positive women].
Cervical intraepithelial lesions associated with genital human papilloma virus (HPV) infection occur with increased frequency and severity among women with immunodeficiency. In this study, we considered 24 HIV-seropositive and 12 HIV-seronegative women. Each woman was interviewed and underwent a cytologic and colposcopic evaluation. Then colposcopic and cytologic findings were correlated with histologic and differences between HIV-seropositives and seronegatives were analyzed. Ten (41%) of 24 HIV-seropositive and one (9%) of 12 HIV-seronegative women had human papilloma virus infection. Among seropositives, eight (34%) had cervical intraepithelial (CIN): of those eight, 5 had CIN I, 2 CIN II and 1 CIN III. There (24%) of the 12 HIV-seronegative had CIN: two had CIN I and one CIN II. Six of the HIV-seropositive women were found to have multicentric disease (two or more sites). The objective of this study is to determine the relationship between human immunodeficiency virus (HIV) and human papilloma virus infection, sexual habits, reproducive history, and risk of cervical intraepithelial neoplasia (CIN). The results of this study suggest that cervical intraepithelial neoplasia is a common finding in HIV-infected women. Papanicolaou tests should be effective for detecting cervical disease in this population.


[Emergency treatment of large amputated ear defect with auricular cartilage replantation].
To investigate the emergency treatment for large amputated ear defect. From Feb. 2010 to Oct. 2013, 5 cases with large unilateral amputated ear defects were treated. The amputated auricular cartilage was replanted subcutaneously in mastoid area at the first stage. Cranioauricular sulcus was reconstructed and skin grafting was performed at the second stage. All cases were followed up for 3-6 months with satisfactory result. The reconstructed helix, scapha and cavity of auricular concha had similar color and elasticity as the ear at healthy side. Scar at donor sites, such as inguinal region and armpit, was inconspicuous. The method of auricular cartilage replantation is an effective way for emergency treatment of large amputated auricular defect with less morbidity at donor site.


Abscisic Acid Negatively Regulates Expression of Chlorophyll a/b Binding Protein Genes during Soybean Embryogeny.
The levels of abscisic acid (ABA) during embryogenesis in the soybean (Glycine max) cultivar Dare were quantitated. An increase in the quantity of ABA per cotyledon was correlated with a decrease in the chlorophyll a/b binding (Cab) protein gene mRNA population. Soybean cotyledons were cultured in vitro in the presence or absence of ABA. Quantitation of cotyledonary ABA levels and Cab mRNA levels indicated that the application of 5 x 10(-5) molar and 5 x 10(-6) molar exogenous ABA decreased Cab mRNA prevalences. S1 nuclease protection experiments demonstrated that exogenous ABA modulated the level of Cab3 mRNA. These data strongly suggest that one of the developmental regulators of Cab gene expression during soybean embryogeny is the plant hormone, ABA; ABA negatively regulates Cab mRNA accumulation.


Dy3+ and Mn2+ emission in fluoride- and chloride-based Na3 (SO4)X (X = F or Cl) phosphors.
In the present study, Na3 (SO4)X (X = F or Cl) halosulphate phosphors have been synthesized by the solid-state diffusion method. The phase formation of the compounds Na3 (SO4)F and Na3 (SO4)Cl were confirmed by X-ray powder diffraction (XRD) measurement. Photoluminescence (PL) excitation spectrum measurement of Na3 (SO4)F:Ce3+ and Na3 (SO4)Cl:Ce3+ shows this phosphor can be efficiently excited by near-ultraviolet (UV) light and presents a dominant luminescence band centred at 341 nm for Ce3+, which is responsible for energy transfer to Dy3+ and Mn2+ ions. The efficient Ce3+ → Dy3+ energy transfer in Na3 (SO4)F and Na3 (SO4)Cl under UV wavelength was observed due to 4 F(9/2) to 6H(15/2) and 6H(13/2) level, while Ce3+ → Mn2+ was observed due to (4) T1 state to (6) A1 . The purpose of the present study is to develop and understanding the photoluminescence properties of Ce3+ -, Dy3+ - and Mn2+ -doped fluoride and chloride Na3 (SO4)X (X = F or Cl) luminescent material, which can be the efficient phosphors in many applications, such as scintillation applications, TL dosimetry and the lamp industry, etc.


[Mediastinal parathyroid cyst].
A 66-year-old woman, having no complaint, admitted our clinic, because of a mass in the right superior mediastinum detected three years ago on chest X-ray. The operation was performed through the right thoracotomy in December of 1989. The thin-walled cyst located adjacent to the trachea between superior vena cava and back bones, occupied from beneath the innominate artery to the right main bronchus. The tumor (7 x 5 x 5 cm) weighing 80 grams had a smooth surface and contained watery fluid. Histological examination showed a cyst lined a monolayer of cuboidal epithelium. The cyst wall consisted of parathyroid tissue. Mediastinal parathyroid cyst is very rare. Since the first report of DeQuervain, 15 cases have been reported. These reports are reviewed.


Diagnostic dilemma of degenerative joint disease, chronic avascular necrosis or metastasis in planar Tc-99m-methylene diphosphonate planar skeletal scintigraphy excluded by single positron emission computed tomography/computed tomography.
We present a 71-year-old male patient subjected to skeletal scintigraphy for metastasis work up of prostate cancer. Whole body planar images revealed a solitary focal tracer uptake in left femoral head mimicking as solitary metastatic focus. Single positron emission computed tomography/computed tomography images localized this increased tracer uptake to the subchondral cysts with minimal sclerosis in left femur head with no decrease in size of femur head and was reported as (degenerative joint disease).


Stochastic instability of quasi-isolated systems.
The stability of solutions to evolution equations with respect to small stochastic perturbations is considered. The stability of a stochastic dynamical system is characterized by the local stability index. The limit of this index with respect to infinite time describes the asymptotic stability of a stochastic dynamical system. Another limit of the stability index is given by the vanishing intensity of stochastic perturbations. A dynamical system is stochastically unstable when these two limits do not commute with each other. Several examples illustrate the thesis that there always exist such stochastic perturbations that render a given dynamical system stochastically unstable. The stochastic instability of quasi-isolated systems is responsible for the irreversibility of time arrow.


Beyond the Born-Oppenheimer approximation: a treatment of electronic flux density in electronically adiabatic molecular processes.
Intuition suggests that a molecular system in the electronic ground state Φ0 should exhibit an electronic flux density (EFD) in response to the motion of its nuclei. If that state is described by the Born-Oppenheimer approximation (BOA), however, a straightforward calculation of the EFD yields zero, since the electrons are in a stationary state, regardless of the state of the nuclear motion. Here an alternative pathway to a nonzero EFD from a knowledge of only the BOA ground-state wave function is proposed. Via perturbation theory a complete set of approximate vibronic eigenfunctions of the whole Hamiltonian is generated. If the complete non-BOA wave function is expressed in the basis of these vibronic eigenfunctions, the ground-state contribution to the EFD is found to involve a summation over excited states. Evaluation of this sum through the so-called "average excitation energy approximation" produces a nonzero EFD. An explicit formula for the EFD for the prototypical system, namely, oriented H2+ vibrating in the electronic ground state, is derived.


Cu-mediated syntheses of N-fused and ring-modified trithiahexaphyrins.
The reaction of the antiaromatic [28]trithiahexaphyrin (TTHP) with Cu(I) in DMF gives a novel fused-ring trithiahexaphyrin with the elimination of a chloride on a dichlorophenyl ring and bond formation to the outward oriented pyrrolic nitrogen to form a 5,5,6-tricyclic internal ring system. The NMR spectra, which display characteristics of an antiaromatic compound, agree with the proposed structure. Meanwhile, reactions of TTHP with amines in the presence of Cu(I) give amino-group-inserted hexaphyrins with the amino nitrogen joined to a beta-thiophenic carbon and the alpha-carbon of the alkylamine cyclized to the inward pyrrolic nitrogen to form a 5,7,5-tricyclic rings. The crystal structure of the fused-ring product indicates a rectangular geometry with a tilted tricyclic ring system, while the ring-modified TTHP-DMA complex gives a triangular trithiahexaphyrin core. This report demonstrates methods to incorporate functionalized heterocyclic rings into expanded porphyrins.


[Effect of sedation on resting energy expenditure in patients with extremely severe burns and the choice of energy estimation formula].
Objective: To investigate the effect of sedation on resting energy expenditure (REE) in patients with extremely severe burns and the choice of REE estimation formula during the treatment. Methods: A retrospective non-randomized controlled clinical study was conducted. From April 2020 to April 2022, 21 patients with extremely severe burns who met the inclusion criteria and underwent mechanical ventilation treatment were admitted to the Department of Burn and Wound Repair of Second Affiliated Hospital of Zhejiang University School of Medicine, including 16 males and 5 females, aged 60 (50, 69) years. Early anti-shock therapy, debridement, skin transplantation, nutritional support, and other conventional treatments were applied to all patients. Patients were sedated when they had obvious agitation or a tendency to extubate, which might lead to aggravation of the disease. REE measurement was performed on patients using indirect calorimetry on post-injury day 3, 5, 7, 9, 11, 14 and every 7 days thereafter until the patient died or being successfully weaned from ventilator. Totally 99 times of measurements were carried out, of which 58 times were measured in the sedated state of patients, and 41 times were measured in the non-sedated state of patients. The age, weight, body surface area, residual wound area, post-injury days of patients were recorded on the day when REE was measured (hereinafter briefly referred to as the measurement day). The REE on the measurement day was calculated with intensive care unit conventional REE estimation formula Thumb formula and special REE estimation formulas for burns including the Third Military Medical University formula, the Peng Xi team's linear formula, Hangang formula. The differences between the sedated state and the non-sedated state in the clinical materials, measured and formula calculated values of REE of patients on the measurement day were compared by Mann-Whitney U test and independent sample t test. The differences between the REE formula calculated values and the REE measured value (reflecting the overall consistency) in the sedated state were compared by Wilcoxon signed rank-sum test. The Bland-Altman method was used to assess the individual consistency between the REE formula calculated value and the REE measured value in the sedated state, and to calculate the proportion of the REE formula calculated value within the range of ±10% of the REE measured value (hereinafter referred to as the accuracy rate). Root mean square error (RMSE) was used to evaluate the accuracy of the REE formula calculated value relative to the REE measured value. Results: Compared with those in the non-sedated state, there was no statistically significant change in patient's age or post-injury days on the measurement day in the sedated state (P>0.05), but the weight was heavier (Z=-3.58, P<0.01), and both the body surface area and the residual wound area were larger (with Z values of -2.99 and -4.52, respectively, P<0.01). Between the sedated state and the non-sedated state, the REE measured values of patients were similar (P>0.05). Compared with those in the non-sedated state, the REE values of patients calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula on the measurement day in the sedated state were significantly increased (with Z values of -3.58 and -5.70, t values of -3.58 and -2.74, respectively, P<0.01). In the sedated state, compared with the REE measured value, there were statistically significant changes in REE values of patients calculated by Thumb formula, the Third Military Medical University formula, and Hangang formula on the measurement day (with Z values of -2.13, -5.67, and -3.09, respectively, P<0.05 or P<0.01), while the REE value of patients calculated by the Peng Xi team's linear formula on the measurement day did not change significantly(P>0.05). The analysis of the Bland-Altman method showed that in the sedated state, compared with the REE measured value, the individual consistency of the calculated value of each formula was good; Thumb formula and Hangang formula significantly underestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of -1 463 and -1 717 kJ/d, the 95% confidence interval of -2 491 to -434 and -2 744 to -687 kJ/d, respectively), but the individual differences were small; the Third Military Medical University formula significantly overestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 3 530 kJ/d, the 95% confidence interval of 2 521 to 4 539 kJ/d), but the individual difference was small; the Peng Xi team's linear formula did not significantly overestimate the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 294 kJ/d, the 95% confidence interval of -907 to 1 496 kJ/d), while the difference standard deviation was 4 568 kJ/d, which showed a large individual difference. In the sedated state, relative to the REE measured value, the accuracy rates of REE values calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula were 25.9% (15/58), 15.5% (9/58), 10.3% (6/58), and 15.5% (9/58), respectively, and RMSE values were 4 143.6, 5 189.1, 4 538.6, and 4 239.8 kJ/d, respectively. Conclusions: Sedative therapy leads to a significant decrease in REE in patients with extremely severe burns undergoing mechanical ventilation treatment. When REE cannot be regularly monitored by indirect calorimetry to determine nutritional support regimens, patients with extremely severe burns undergoing sedation may be prioritized to estimate REE using Thumb formula.


Immunomodulatory Layered Double Hydroxide Nanoparticles Enable Neurogenesis by Targeting Transforming Growth Factor-β Receptor 2.
Immune microenvironment amelioration and reconstruction by functional biomaterials has become a promising strategy for spinal cord injury (SCI) recovery. In this study, we evaluated the neural regeneration and immunoregulation functions of Mg/Al layered double hydroxide (Mg/Al-LDH) nanoparticles in completely transected and excised mice and revealed the immune-related mechanisms. LDH achieved significant performance in accelerating neural stem cells (NSCs) migration, neural differentiation, L-Ca2+ channel activation, and inducible action potential generation. In vivo, the behavioral and electrophysiological performance of SCI mice was significantly improved by LDH implantation, with BrdU+ endogenous NSCs and neurons clearly observed in the lesion sites. According to RNA-seq and ingenuity pathway analysis, transforming growth factor-β receptor 2 (TGFBR2) is the key gene through which LDH inhibits inflammatory responses and accelerates neural regeneration. Significant colocalization of TGFBR2 and LDH was found on the cell membranes of NSCs both in vitro and in vivo, and LDH increased the expression of TGF-β2 in NSCs and activated the proliferation of precursor neural cells. LDH decreased the expression of M1 markers and increased the expression of M2 markers in both microglia and bone marrow-derived macrophages, and these effects were reversed by a TGFBR2 inhibitor. In addition, as a carrier, LDH loaded with NT3 exhibited better recovery effects with regard to the basso mouse scale score, motor evoked potential performance, and regenerated neural cell numbers than LDH itself. Thus, we have developed Mg/Al-LDH that can be used to construct a suitable immune microenvironment for SCI recovery and have revealed the targeted receptor.


Triptolide Shows High Sensitivity and Low Toxicity Against Acute Myeloid Leukemia Cell Lines Through Inhibiting WSTF-RNAPII Complex.
Triptolide exhibits superior and broad-spectrum antitumor activity. However, the narrow safety window caused by the toxicity of triptolide limits its clinical applications. Although several characterized targets for triptolide are reported, the association between triptolide and its targets in cancer therapy is not fully understood. Here, we show that acute myeloid leukemia (AML) cell lines are sensitive to triptolide by constructing an in vitro cell and in vivo xenograft models. Meanwhile, the triptolide-induced hepatotoxicity increases with increasing dosages within the xenograft models. Additionally, the expression levels of WSTF-RPB1 are strongly associated with the sensitivity to triptolide in hematological cancer cells and can be downregulated in a dose and time-dependent manner. Finally, we show that optimizing dosing regimens can achieve the same pharmaceutical effect and reduce toxicity. In summary, this study aims to search for triptolide-sensitive cell lines as well as the underlying molecular mechanisms in order to broaden the safety window of triptolide; thus, increasing its clinical utility.


Comparison of Duration of Analgesic Comparison of Duration of Analgesic Effect of Nalbuphine and Morphine as an Adjuvant to Bupivacaine in the Supraclavicular Block under Ultrasound Guidance.
Although many studies are available in the literature that has analyzed the effects of morphine, nalbuphine, and other opioids, no study had compared the effects of nalbuphine versus morphine as an adjuvant to bupivacaine in the supraclavicular block under the guidance of ultrasound. A randomized, double-blinded, prospective study was carried out on 60 patients of the American Society of Anesthesiologists Class I and II who were undergoing upper limb surgeries under the supraclavicular block. Patients were randomly allocated into two groups (n = 30). Group N received 20 ml of 0.5% bupivacaine with 50 μg.kg-1 of nalbuphine, while Group M received 20 ml of 0.5% bupivacaine with 50 μg.kg-1 of morphine. The characteristics of sensory and motor blocks, hemodynamic changes, duration of analgesia, adverse effects, and analgesic requirements were studied at different time intervals. In Group N, there was a statistically significant reduction in the time of onset of sensory block (9.9 ± 3.0 vs. 12.2 ± 2.6 min, P = 0.002) and motor block (14.4 ± 3.6 vs. 19.4 ± 3.6 min, P = 0.0005). The duration of sensory and motor blockade and duration of analgesia were comparable. There was no statistically significant difference regarding block characteristics and hemodynamic parameters. Nalbuphine when added to bupivacaine as an adjuvant had significantly shortened the time of onset of sensory and motor blockade than morphine. However, the duration of analgesia, sensory and motor blockade of nalbuphine versus morphine were comparable.


Community Perspectives in Medicine: Elective for First-Year Medical Students.
Recently, stories depicting social injustices and inequities have gripped the US, leading to protests and other demonstrations of student activism. In response to current events, students at Weill Cornell Medical College identified the need for more diversity inclusion components in the newly developed medical school curriculum. Thus, we developed a student-initiated, student-run elective, Community Perspectives in Medicine, which provides a forum for first-year medical students to interact, and have open discussions, with members of communities most impacted by social and health inequities. During five weekly 2-hour sessions, representatives of different community-based organizations (CBOs) speak with 15 first-year medical students. Invited CBOs represent diverse populations, including LGBT, chronic illness, disabilities, religion, and immigrant health. For each session's first hour, a second-year student facilitates a semistructured interview of the CBO guests focusing on health disparities within their community, challenges experienced with the medical system, and what they wish doctors did differently. Students are encouraged to ask questions, often resulting in a rich dialogue. The session's second part is a debriefing by the student facilitator over a relaxed dinner (without CBO guests). Fourteen of the16 enrolled students attended all five sessions and completed the course evaluation. Satisfaction with the course was high, as 93% of students enrolled rated the course as excellent. The course format, content, and diversity of speakers were rated as excellent by 79%, 86%, and 93%, respectively. Similarly, 71% of students believed there to be excellent applicability to medical practice, and 100% of students thought the timing during first year was excellent. We emphasize the importance of a partnership between CBOs and medical students, thus increasing students' cultural awareness as well as formally involving traditionally disenfranchised communities in medical education. Our project's unique format of safe-space discussion forums and session debriefings enhances critical thinking. Though used with multiple CBOs as an elective, our model can be easily adapted for one session on a specific health disparity.


[Serum-free culture of umbilical cord mesenchymal stem cells].
This study was purposed to observe the culture of umbilical cord mesenchymal stem cells (UC-MSC) with serum-free medium, and compared it with the medium containing 10% fetal bovine serum (FBS). The normal umbilical cords were acquired during cesarean section, and then were cultured with MesenCult-XF serum-free medium or medium containing 10% fetal bovine serum (FBS). The morphology, immunophenotype, cell cycle, proliferation and differentiation potential of mesenchymal stem cells and the inhibition of mixed lymphocyte reaction were observed through different medium culture method. The results showed that the MSC cultured with serum-free MesenCult(-)XF medium could transfer and multiply for average of 6.57 ± 0.7 times, and the serum medium-cultured MSC could transfer and multiply for average of 4.59 ± 0.45 times (P < 0.05). Two kinds of medium cultured MSC all expressed CD44, CD90, CD73, CD105 antigen, but did not expressed CD31, CD45, HLA-DR and CD34 antigen, and their expression levels were not significantly different. The serum-free medium-cultured MSC (65 ± 5.2%) were all at Go/G1 phase, and the serum-contained medium-cultured MSC (62+3.1%) were at Go/G1 phase(P > 0.05); the 2 kinds of media-cultured MSC all could differentiate into fat and ossification; when serum-free medium cultured umbilical cord MSC were inoculated at the the density of 10(3), 5×10(3), 10(4), and 2×10(4) cells/well, then co-cultured with the reactant and stimulating cells, the CPM were (6.43 ± 0.47)×10(4), (4.30 ± 0.38)×10(4), (1.97 ± 0.13)×10(4) and (0.24 ± 0.03)×10(4), respectively, and the serum-containing medium-cultured MSC were incubated with different density of mixed lymphocyte, displaying CPM that were (7.85 ± 0.07)×10(4), (5.64 ± 0.12)×10(4), (3.09 ± 0.18)×10(4) and (1.73 ± 0.05)×10(4). It is concluded that the serum-free medium has been confirmed to culture MSC, which have potential of transfer and differentiation with count for clinical application, and can avoid foreign protein sensitization.


Theoretical comparison of illumination and collection mode images of magneto-optical dots.
We compare theoretical images of the same sample obtained with two different scanning near-field optical microscopes. The sample is a two-dimensional periodic array of magnetic sub-micrometric dots. The magnetization is perpendicular to the sample plane (polar magnetization). The first configuration is a scanning tunnelling optical near-field microscope (STOM) where the tip is used in the detection mode and the sample is illuminated by total internal reflection. The second configuration is an inverted STOM: the tip is used in the emission mode and the diffracted field is far-field detected in one direction. We present the models used to describe the two configurations and then explain the main lines of the formalism used to calculate the diffracted fields by a magneto-optical sample.


alpha-1-antichymotrypsin interaction with A beta (1-40) inhibits fibril formation but does not affect the peptide toxicity.
Recent studies have shown that senile plaque-associated or glial-derived proteins can prevent fibril formation of beta-amyloid peptide (A beta), while increasing the neurotoxicity of the latter (in the case of glutamine synthetase, apolipoprotein J or thrombin). alpha-1-Antichymotrypsin (ACT) is a glial-derived protein associated with senile plaques in the Alzheimer's brain. In this report we show that ACT, a minor protein component of beta-amyloid deposits, is able to inhibit A beta (1-40) aggregation into fibrils, but unable to modulate the toxicity of A beta (1-40) in primary rat hippocampal cell cultures. These results are discussed in terms of the potential role of glial-derived proteins on A beta aggregation and neurotoxicity.


Diabetes, kidney disease and cardiovascular disease patients. Assessing care of complex patients using outpatient testing and visits: additional metrics by which to evaluate health care system functioning.
The triad of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetes mellitus (DM) share many fundamental disease pathways. Patients with these conditions contribute excessively to health care costs. Opportunities for system redesign require metrics by which to evaluate the impact. Using a provincial comprehensive set of administrative billing databases (outpatient visits, laboratory tests, pharmacy and hospital inpatient services), we itemized the prevalence of each and combination of conditions, resource utilization associated with each condition and combinations, using ICD 9-10 billing codes and standard definitions. Three consecutive years (2003-2005) were used to establish stability of findings. CKD, CVD and DM diagnoses are found in 422 124 persons within a province of 4.3 million individuals (10%); 1.7% had all three conditions. The median age of each cohort varied significantly between those with multiple conditions (67-79 years) versus those with single condition (56-72 years). The median number of physician visits was 26 per patient year. Duplicate testing accounted for expenditures of $3 million/annum; 7.55% of patients accounted for 34.4% of duplicate tests. Those with DM or CKD had similar use of medications, physician visits and hospital days. Those with all conditions (CVD-CKD-DM) had a median of 6 in-hospital days/year. A significant proportion were not on ACE/ARB or statin medications (30 and 45%, respectively). Patients with chronic, complex conditions consume a large number of outpatient and inpatient resources. Documenting these allows identification of a set of metrics by which to design and measure health care system redesign initiatives. Potential targets to benchmark in designing more effective systems have been identified.


Exogenous serotonin and gastric mucosal blood flow in conscious dogs.
The effects of serotonin on pentagastrin- and bethanechol-stimulated gastric mucosal blood flow (GMBF) and acid secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method to estimate the mucosal blood flow. Serotonin inhibited the acid secretion, with a counteracting effect of propranolol and methysergide. Serotonin inhibited the pentagastrin- and bethanechol-stimulated GMBF after 15 min of infusion. The ratio between GMBF and acid secretion was increased during serotonin infusion, which suggests primary and independent changes in both variables. Propranolol and methysergide counteracted the serotonin inhibition of the GMBF. It may be concluded from this study that the acid-inhibitory effect of serotonin is not mediated by changes in the GMBF. The actions of serotonin on acid secretion and GMBF are mediated by specific receptors.


Investigation of the binding of AuNPs-6-mercaptopurine and the sensitive detection of 6-mercaptopurine using resonance Rayleigh light scattering.
A highly sensitive method for the detection of 6-mercaptopurine (MP) by resonance Rayleigh light scattering (RLS) method was developed. Gold nanoparticles (AuNPs) were synthesized by a modified seed method and characterized using transmission electron microscopy (TEM). AuNPs were bound to MP via covalent bonding to form the MP-AuNPs complex, which increased the RLS intensity of MP at 347 nm (increased by 65.7%). Under optimum conditions, the magnitude of the enhanced RLS intensity for MP-AuNPs was proportional to MP concentration in the range 0.0681-1.702 μg mL-1 . The linear regression equation was represented as follows: ΔIRLS = 9.31 + 82.42c (r = 0.9948). The limit of detection (LOD, 3σ) was 3.32 ng mL-1 . The system was applied successfully to detect MP in pharmaceuticals. MP recoveries were 99.9-101.7% with a relative standard deviation (RSD) (n = 5) of 0.59-0.77% for three synthetic samples, and 97.5-110.0% with an RSD of 0.98-2.10% (n = 5) for tablet samples.


Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke.
Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation, histone methylation, etc. Changes in DNA methylation after ischemia can have both neuroprotective and neurotoxic effects depending on the degree of ischemia damage, the time elapsed after injury, and the site of methylation. In this study, we investigated the changes in the expression and intracellular localization of DNA methyltransferase DNMT1, histone methyltransferases SUV39H1, and G9a in penumbra neurons and astrocytes at 4 and 24 h after stroke in the rat cerebral cortex using photothrombotic stroke (PTS) model. Methods of immunofluorescence microscopy analysis, apoptosis analysis, and immunoblotting were used. Additionally, we have studied the effect of DNMT1 and G9a inhibitors on the volume of PTS-induced infarction and apoptosis of penumbra cells in the cortex of mice after PTS. This study has shown that the level of DNMT1 increased in the nuclear and cytoplasmic fractions of the penumbra tissue at 24 h after PTS. Inhibition of DNMT1 by 5-aza-2'-deoxycytidine protected cells of PTS-induced penumbra from apoptosis. An increase in the level of SUV39H1 in the penumbra was found at 24 h after PTS and G9a was overexpressed at 4 and 24 h after PTS. G9a inhibitors A-366 and BIX01294 protected penumbra cells from apoptosis and reduced the volume of PTS-induced cerebral infarction. Thus, the data obtained show that DNA methyltransferase DNMT1 and histone methyltransferase G9a can be potential protein targets in ischemic penumbra cells, and their inhibitors are potential neuroprotective agents capable of protecting penumbra cells from postischemic damage to the cerebral cortex.


Regioselective aerobic oxidative Heck reactions with electronically unbiased alkenes: efficient access to α-alkyl vinylarenes.
Branched-selective oxidative Heck coupling reactions have been developed between arylboronic acids and electronically unbiased terminal alkenes. The reactions exhibit high catalyst-controlled regioselectivity favoring the less common branched isomer. The reactions employ a catalyst composed of Pd(TFA)2/dmphen (TFA = trifluoroacetate, dmphen = 2,9-dimethyl-1,10-phenanthroline) and proceed efficiently at 45-60 °C under 1 atm of O2 without requiring other additives. A broad array of functional groups, including aryl halide, allyl silane and carboxylic acids are tolerated.


[Program for helping the smoker in primary care. Preliminary evaluation].
The program of help to the smoker (PHS) consists of a systematic intervention upon the whole of the demanding population, identifying the smokers and acting on them with a short, concise advise in all visits. The results after 2 months of operation of the PHS in a primary care center are reported. Among 483 persons 104 smokers were detected (23.65%). 27% showed a favorable disposition towards quitting smoking within a short term; only 17% declared to be against quitting. The best response (36.8% of favorable responses) was obtained in the group smoking 20 cigarettes per day or more. The reported data suggest that the PHS could be useful both in heavy and in minimal or moderate smokers. We consider these data as a preliminary evaluation; assessment with data of long term cessation from smoking is required.


Exploration and comparison of bacterial communities present in bovine faeces, milk and blood using 16S rRNA metagenomic sequencing.
Cattle by-products like faeces, milk and blood have many uses among rural communities; aiding to facilitate everyday household activities and occasional rituals. Ecologically, the body sites from which they are derived consist of distinct microbial communities forming a complex ecosystem of niches. We aimed to explore and compare the faecal, milk and blood microbiota of cows through 16S rRNA sequencing. All downstream analyses were performed using applications in R Studio (v3.6.1). Alpha-diversity metrics showed significant differences between faeces and blood; faeces and milk; but non-significant between blood and milk using Kruskal-Wallis test, P < 0,05. The beta-diversity metrics on Principal Coordinate Analysis and Non-Metric Dimensional Scaling significantly clustered samples by type (PERMANOVA test, P < 0,05). The overall analysis revealed a total of 30 phyla, 74 classes, 156 orders, 243 families and 408 genera. Firmicutes, Bacteroidota and Proteobacteria were the most abundant phyla overall. A total of 58 genus-level taxa occurred concurrently between the body sites. The important taxa could be categorized into four potentially pathogenic clusters i.e. arthropod-borne; food-borne and zoonotic; mastitogenic; and metritic and abortigenic. A number of taxa were significantly differentially abundant (DA) between sites based on the Wald test implemented in DESeq2 package. Majority of the DA taxa (i.e. Romboutsia, Paeniclostridium, Monoglobus, Akkermansia, Turicibacter, Bacteroides, Candidatus_Saccharimonas, UCG-005 and Prevotellaceae_UCG-004) were significantly enriched in faeces in comparison to milk and blood, except for Anaplasma which was greatly enriched in blood and was in turn the largest microbial genus in the entire analysis. This study provides insights into the microbial community composition of the sampled body sites and its extent of overlapping. It further highlights the potential risk of disease occurrence and transmission between the animals and the community of Waaihoek in KwaZulu-Natal, Republic of South Africa pertaining to their unsanitary practices associated with the use of cattle by-products.


Assessment of a rapid HIV test strategy during labor: a pilot study from Rio de Janeiro, Brazil.
To use two rapid human immunodeficiency virus (HIV) tests at labor, measure test acceptance and performance, and measure HIV prevalence in these women. Between February and October 2000, two rapid tests (Determine; Abbott, Chicago, IL, U.S.A. and Double Check; Orgenics, Yavne, Israel) were used in three public maternities in Rio de Janeiro, Brazil. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis confirmed positive and discordant results. Of the 858 patients who were enrolled, the mean gestational age was 36 weeks (median = 39, mode = 40) and 17 (2%) refused testing. Of the 841 patients tested, 13 were positive by both tests, which represents a 1.5% prevalence (95% confidence interval: 0.7%-2.3%); all were confirmed by ELISA and WB analysis. Seven samples gave discordant results by the rapid tests; of these, six were ELISA-negative/WB-negative and one was ELISA-negative/WB-indeterminate. The positive predictive value for samples that were positive by both rapid tests simultaneously was 100%. Two rapid HIV tests used at labor were well accepted (98%). When the combined results of the two rapid tests (but not a single rapid test) were analyzed, this strategy was as efficient as the standard ELISA and WB HIV strategy for correctly classifying individuals.


Bilateral renal cortical necrosis in meningococcal meningitis.
Bacterial meningitis is a relatively common infection of the cerebrospinal fluid (CSF) and leptomeninges. The clinical picture evolves rapidly and, if treatment is delayed, can result in a variety of long-term sequelae, including death. Acute kidney injury in the setting of bacterial meningitis usually results from hypotension and volume depletion and resolves with appropriate treatment. Meningococcaemia with profound hypotension, and/or disseminated intravascular coagulopathy (DIC) may very rarely lead to bilateral renal cortical necrosis. In this context, renal recovery is extremely unlikely. We present two cases of meningococcaemia complicated by bilateral renal cortical necrosis and, ultimately, end stage kidney disease. We also present a review of the literature on the subject. The cases outline the importance of early aggressive intervention by a multidisciplinary team.


Recent performance of the SNS H(-) ion source and low-energy beam transport system.
Recent measurements of the H(-) beam current show that SNS is injecting about 55 mA into the RFQ compared to ∼45 mA in 2010. Since 2010, the H(-) beam exiting the RFQ dropped from ∼40 mA to ∼34 mA, which is sufficient for 1 MW of beam power. To minimize the impact of the RFQ degradation, the service cycle of the best performing source was extended to 6 weeks. The only degradation is fluctuations in the electron dump voltage towards the end of some service cycles, a problem that is being investigated. Very recently, the RFQ was retuned, which partly restored its transmission. In addition, the electrostatic low-energy beam transport system was reengineered to double its heat sinking and equipped with a thermocouple that monitors the temperature of the ground electrode between the two Einzel lenses. The recorded data show that emissions from the source at high voltage dominate the heat load. Emissions from the partly Cs-covered first lens cause the temperature to peak several hours after starting up. On rare occasions, the temperature can also peak due to corona discharges between the center ground electrode and one of the lenses.


Safety of the posterior approach in adrenal surgery: experience in 105 cases.
At the advent of laparoscopic adrenalectomy when it was timely to reappreciate the results of time-honored procedures, we reviewed the cases of 105 patients who underwent adrenalectomy through the posterior approach. Between 1970 and 1992 among 331 patients, 105 underwent adrenalectomy through the posterior approach (0 of 111 pheochromocytomas, 48 of 64 Conn's disease, 37 of 57 Cushing's disease, 2 of 20 virilizing-feminizing tumors, 13 of 61 nonsecreting adrenalomas, 3 of 12 metastases, 2 of 6 cysts). Adrenalectomy was bilateral in 20 cases. Among 86 tumors, 28 (32.6%) were larger than 5 cm in diameter, none exceeding 10 cm. Posterior approach, initially performed in the prone position, was used in the lateral position for the last 40 patients with tumors. A hockey-stick incision was made on the twelfth or eleventh rib, which was resected. During operation no patient died; one minimal caval tear and 13 pleural tears occurred and were sutured, with two pleural drainages; six patients received blood transfusion. Average operative time was 132 minutes (range, 45 to 290 minutes). After operation one patient died of iatrogenic sepsis, average time to ambulation was 1.5 days, and average in-hospital stay was 7.6 days (range, 1 to 21), which after the fourth day was mostly justified for nonsurgical reasons. From 1990 through 1992, 37 of 38 patients were walking the day after operation and average postoperative stay dropped to 4.5 days (range, 1 to 7 days). Adrenalectomy through the posterior approach is safe and allows early postoperative discharge.


User Perspectives of a Web-Based Data-Sharing Platform (Open Humans) on Ethical Oversight in Participant-Led Research: Protocol for a Quantitative Study.
Advances in medicine rely to a great extent on people's willingness to share their data with researchers. With increasingly widespread use of digital technologies, several Web-based communities have emerged aiming to enable their users to share large amounts of data, some of which can possibly be employed for research purposes by scientists, or to conduct participant-led research (PLR). Scholarship has recently addressed the necessity of interrogating how existing ethical standards can and should be applied and adapted in view of the specificities of such Web-based activities. So far, no study has explored participants' beliefs about and attitudes toward ethical oversight when it comes to platforms that involve medical data sharing. This paper presents the protocol for a survey study aimed at understanding users' beliefs about Web-based data-sharing platforms regarding how research ethics principles should be applied in such a setting. Furthermore, the study aims at quantitatively assessing the relationship between participants' perspectives on ethical oversight and other variables such as previous participation in research, beliefs about data sharing, and attitudes toward self-experimentation. We are conducting a Web-based survey with users of a popular Web-based data-sharing platform, Open Humans. The survey has been sent to approximately 4640 users registered for the Open Humans newsletter. To fill out the survey, participants need to have an account on Open Humans. We expect a 5%-10% response rate (between 200 and 400 completed surveys out of approximately 4000 survey invitations sent). Independent variables include past data-sharing behavior and intention, beliefs about data sharing, past participation in research, attitudes toward self-experimentation, perceived knowledge of the platform's guidelines and terms, perceived importance of having transparent guidelines, and governance-related beliefs. The main dependent variable is participants' expectations regarding who should ensure that ethical requirements are met within research projects conducted on open data-sharing platforms, based on Emanuel et al's ethical framework. We will use chi-square tests to assess the relationship between participants' expectations regarding ethical oversight and their past behavior, future intentions, beliefs, attitudes, and knowledge. Data collection started on June 13, 2018. A reminder to fill out the survey was sent to participants in mid-July. We expect to gain insights on users' perspectives on the ethical oversight of Web-based data-sharing platforms and on the associated experiences, beliefs, and sociodemographic characteristics. When digital tools allow people to engage in PLR including medical data, understanding how people interpret and envision the ethical oversight of their data-sharing practices is crucial. This will be the first study to explore users' perspectives on ethical oversight of Web-based data-sharing platforms. The results will help inform the development of a framework that can be employed for platforms hosting various kinds of research projects to accommodate participants' ethical oversight needs. RR1-10.2196/10939.


Primary surgical management of anterior pelvic organ prolapse: a systematic review, network meta-analysis and cost-effectiveness analysis.
Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available. To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP. We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective. We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values. Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty. New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse.


[Spinal reflexes in the determination of brain death].
The authors present the results of spinal cord function evaluation in organ donors by examination of reflexes. The knee reflex and ankle jerk, as well as abdominal reflex and foot withdrawal reaction were tested in 31 donors. At least one of the above was seen in 25 individuals. It is suggested on the basis of data obtained not to hamper the transplant procedure in cases of tested reflex persistency when brain death is revealed on relevant examination.


Hydrogen Bond-Enhanced Nanoaggregation and Antisolvatochromic Fluorescence for Protein-Recognition by Si-Coumarins.
Silicon-substituted coumarin (SiC) was established as a substantial family of both intramolecular and intermolecular hydrogen bond (H-bond) enhanced fluorescent probes for sensitively tracking proteins in vivo through the assemble and disassemble of its nanoaggregates. The intramolecular H-bond in SiC has led to significant aggregation, antisolvatochromism, and strong fluorescence with bathochromically shifted spectra into far-red or near-infrared (NIR) regions in polar, protic environments. Without further furnishing with organic linkers, the compact skeleton of SiC bearing H-bond has ensured sensitively and selectively sensing the targeting proteins with the protic reaction pockets through efficient disassemble of the aggregates. In the existence of strong intermolecular H-bonds with the target protein pocket, SiC resolved as high as >250-fold fluorescence enhancement. Selectively tracking proteins, including human serum albumin, human carbonic anhydrase (hCAII), avidin, SNAP-tag protein, and translocator protein, has confirmed SiC a versatile skeleton for sensitively monitoring proteins in complicated biological systems.


Understanding the influence of Mg doping for the stabilization of capacity and higher discharge voltage of Li- and Mn-rich cathodes for Li-ion batteries.
Although Li- and Mn-rich layered cathodes exhibit high specific capacity, the cathode materials of the general formula Li1+x[NiyMnzCow]O2 (x + y + z + w = 1) suffer from capacity fading and discharge-voltage decay during prolonged cycling, due to the layered-to-spinel transformation upon cycling to potentials higher than 4.5 V vs. Li. In this paper, we study the effect of Mg doping (by partial replacement of Mn ions) on the electrochemical performance of Li- and Mn-rich cathodes in terms of specific capacity, capacity retention and discharge voltage upon cycling. Mg-doped Li- and Mn-rich Li1.2Ni0.16Mn0.54Mg0.02Co0.08O2 and Li1.2Ni0.16Mn0.51Mg0.05Co0.08O2 cathode materials were synthesized by a self-combustion reaction (SCR), and their electrochemical performance in Li-ion batteries was tested. The replacement of a small amount of Mn ions by Mg ions in these materials results in a decrease in their specific capacity. The doping of a small amount of Mg (x = 0.02) resulted only in the stabilization of the capacity, whereas a greater amount (x = 0.05) resulted in improved capacity retention and discharge voltage upon cycling. Li1.2Ni0.16Mn0.51Mg0.05Co0.08O2 exhibits a low specific capacity of about 160 mA h g-1, which increases and then stabilizes at about 230 mA h g-1, and finally decreases to 210 mA h g-1 during 100 cycles. The substitution of Mg for Mn (x = 0.05) results in a higher discharge voltage than the other two cathode materials examined in this study. Structural analysis of the cycled electrodes suggests that Mg suppresses the activation of Li2MnO3 during the initial cycling, and hence, partially prevents layered-to-spinel transformation, resulting in a better electrochemical performance of the Mg-doped cathode material as compared to the undoped material.


Developing interactive and simple electromyogram PONG game for foot dorsiflexion and plantarflexion rehabilitation exercise.
Gaming systems have been proven to be able to improve physical and cognitive skills. Several studies have integrated games to be part of rehabilitation program to improve functional ability of human limbs in performing activities of daily living. This paper presents the development of an interactive electromyogram (EMG) based PONG game for foot dorsifexion and plantarflexion exercise. PONG game is selected because it is a classical game that can be easily comprehended and can be played by young and old people. Two surface EMG sensors were used in this work to acquire muscle activity of tibialis anterior muscle and gastrocnemius muscle. An experimental study was carried out to examine the viability of this sensor as input to play the game. The results were satisfactory. This study further strengthens the viability of using muscle activity as an input for gaming system and as a mean to monitor patient rehabilitation progress.


BIACORE data processing: an evaluation of the global fitting procedure.
Data from real-time molecular interaction analysis using BIACORE are currently evaluated by numerical integration. We have investigated the ability of two software packages (BIAevaluation 3.0 and CLAMP99) to analyze complex interactions. Three experimental data sets of high quality obtained with BIACORE upgraded and 2000 instruments, representative of simple bimolecular, heterogeneous ligand, and mass-transport-limited interactions, were processed by the global fitting procedure. The two software, which differ mainly in the statistical assessment of the output values, were able to discriminate correctly between various interacting models and provided very close output parameters with satisfactory statistical tests.


Pre-treatment Serum HE4 Level as a Novel Independent Prognostic Biomarker for Uterine Cervical Carcinoma Patients.
In spite of the effective implementation of screening programs, uterine cervical carcinoma (UCC) remains one of the major causes of cancer death among women around the world. The aim of this study was to investigate the prognostic value of serum human epididymis protein 4 (HE4) in UCC. Pre-treatment serum samples from 109 UCC patients and 99 healthy women were analyzed for HE4 levels by a quantitative chemiluminescent microparticle immunoassay on the automated ARCHITECT instrument. HE4 serum (sHE4) levels were significantly higher in UCC patients, regardless of tumor stage, compared with healthy controls. Elevated sHE4 levels were significantly associated with advanced FIGO stage and absence of disease-free interval after treatment. In univariable analysis, higher sHE4 levels were significantly correlated with shorter overall survival and progression-free survival. In multivariable analysis, sHE4 retained its significance as independent adverse prognostic factor for both survival endpoints. This study indicates that sHE4 is associated with a more aggressive tumor phenotype and a worse patient's prognosis. These results suggest the potential role of sHE4 as a novel prognostic marker and as an indicator of high-risk UCC patients for a tailored surgical and adjuvant therapy.


Prevalence and mechanisms of linezolid resistance among staphylococcal clinical isolates from Egypt.
The emergence of methicillin-resistant staphylococci necessitated the search for alternative agents as linezolid, introduced to treat infections due to multidrug-resistant bacteria. Linezolid resistance has since emerged, yet its global prevalence remains low. In Egypt, little is known about the situation. We investigated the prevalence and mechanisms of resistance among Egyptian staphylococcal clinical isolates. Linezolid resistance among 232 staphylococcal isolates obtained from Alexandria Main Hospitals between 2011 and 2016 was assessed using disc diffusion and minimum inhibitory concentration. Resistant isolates were checked for cfr presence using polymerase chain reaction. The V domain of different alleles of 23S rRNA gene was investigated for mutations. Selection for linezolid-resistant mutants was performed in vitro through serial passages in linezolid sub-inhibitory concentrations. Combinations of linezolid with imipenem or anti-inflammatory agents were investigated using time-kill and modified checkerboard assays. Three Staphylococcus haemolyticus isolates (1.3%) from 2015 to 2016 were linezolid-resistant. One isolate carried cfr which was plasmid-borne, and together with another isolate which had a G2603T point mutation in the V domain of 23S rRNA gene. Successive exposure to linezolid sub-inhibitory concentrations was selected for three resistant Staphylococcus aureus mutants out of ten susceptible isolates. These mutants were more resistant towards different antibiotic classes than their susceptible parents. Linezolid combinations with imipenem, ibuprofen, or aspirin were synergistic against the isolates and mutants. Despite unregulated use of linezolid, resistance remains fairly low among the Egyptian isolates. Strict antimicrobial stewardship guidelines are needed in hospitals and the community to guard against further evolution of resistant mutants.


Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity.
In cultured renal epithelial cells, exposure to oxalate, a constituent of many kidney stones, elicits a cascade of responses that often leads to cell death. Oxalate toxicity is mediated via generation of reactive oxygen species (ROS) in a process that depends at least in part upon lipid signaling molecules that are generated through membrane events that culminate in phospholipase A2 (PLA2) activation. The present studies asked whether mitochondria, a major site of ROS production, were targets of oxalate toxicity, and if so, whether mitochondrial responses to oxalate were mediated by PLA2 activation. Effects of oxalate and various lipids on mitochondrial membrane potential (DeltaPsim) were measured in Madin-Darby canine kidney (MDCK) cell monolayers using 5,5',6,6'-tetrachloro 1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), a DeltaPsim-sensitive dye. Other studies assayed caspases, serine proteases activated during apoptosis, in response to oxalate or lipid signaling molecules. Additional studies asked whether oxalate or lipids produced by PLA2 activation promoted ROS formation in isolated renal mitochondria. Oxalate exposure decreased MDCK cell DeltaPsim within 30 minutes, a response attenuated by arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2 (cPLA2). Exposure to arachidonic acid or to lysophosphatidylcholine (lyso-PC), lipid products of PLA2 activation, or to ceramide, another lipid signal generated in MDCK cells following oxalate exposure, also depolarized MDCK cell DeltaPsim and increased the number of caspase-positive cells. Isolated renal mitochondria responded to oxalate, arachidonic acid, lyso-PC, and ceramide by increasing their accumulation of ROS, lipid peroxides, and oxidized thiol proteins. These studies suggest that lipid signaling molecules released after oxalate-induced PLA2 activation trigger marked, rapid changes in mitochondrial function that may mediate toxicity in renal epithelial cells.


Role of diffusion-weighted magnetic resonance imaging in the differential diagnosis of focal hepatic lesions.
To evaluate the utility of diffusion-weighted imaging (DWI) in screening and differential diagnosis of benign and malignant focal hepatic lesions. Magnetic resonance imaging (MRI) examinations were performed using the Signa Excite Xl Twin Speed 1.5T system (GE Healthcare, Milwaukee, WI, USA). Seventy patients who had undergone MRI of the liver [29 hepatocellular carcinomas (HCC), four cholangiocarcinomas, 34 metastatic liver cancers, 10 hemangiomas, and eight cysts] between April 2004 and August 2008 were retrospectively evaluated. Visualization of lesions, relative contrast ratio (RCR), and apparent diffusion coefficient (ADC) were compared between benign and malignant lesions on DWI. Superparamagnetic iron oxide (SPIO) was administered to 59 patients, and RCR was compared pre- and post-administration. DWI showed higher contrast between malignant lesions (especially in multiple small metastatic cancers) and surrounding liver parenchyma than did contrast-enhanced computed tomography. ADCs (mean +/- SD x 10(-3) mm(2)/s) were significantly lower (P < 0.05) in malignant lesions (HCC: 1.31 +/- 0.28 and liver metastasis: 1.11 +/- 0.22) and were significantly higher in benign lesions (hemangioma: 1.84 +/- 0.37 and cyst: 2.61 +/- 0.45) than in the surrounding hepatic tissues. RCR between malignant lesions and surrounding hepatic tissues significantly improved after SPIO administration, but RCRs in benign lesions were not improved. DWI is a simple and sensitive method for screening focal hepatic lesions and is useful for differential diagnosis.


Clinical Importance of Incidental Homogeneous Renal Masses That Measure 10-40 mm and 21-39 HU at Portal Venous Phase CT: A 12-Institution Retrospective Cohort Study.
BACKGROUND. Incidental homogeneous renal masses are frequently encountered at portal venous phase CT. The American College of Radiology Incidental Findings Committee's white paper on renal masses recommends additional imaging for incidental homogeneous renal masses greater than 20 HU, but single-center data and the Bosniak classification version 2019 suggest the optimal attenuation threshold for detecting solid masses should be higher. OBJECTIVE. The purpose of this article is to determine the clinical importance of small (10-40 mm) incidentally detected homogeneous renal masses measuring 21-39 HU at portal venous phase CT. METHODS. We performed a 12-institution retrospective cohort study of adult patients who underwent portal venous phase CT for a nonrenal indication. The date of the first CT at each institution ranged from January 1, 2008, to January 1, 2014. Consecutive reports from 12,167 portal venous phase CT examinations were evaluated. Images were reviewed for 4529 CT examinations whose report described a focal renal mass. Eligible masses were 10-40 mm, well-defined, subjectively homogeneous, and 21-39 HU. Of these, masses that were shown to be solid without macroscopic fat; classified as Bosniak IIF, III, or IV; or confirmed to be malignant were considered clinically important. The reference standard was renal mass protocol CT or MRI, ultrasound of definitively benign cysts or solid masses, single-phase contrast-enhanced CT or unenhanced MRI showing no growth or morphologic change for 5 years or more, or clinical follow-up 5 years or greater. A reference standard was available for 346 masses in 300 patients. The 95% CIs were calculated using the binomial exact method. RESULTS. Eligible masses were identified in 4.2% of patients (514/12,167; 95% CI, 3.9-4.6%). Of 346 masses with a reference standard, none were clinically important (0%; 95% CI, 0-0.9%). Mean mass size was 17 mm; 72% (248/346) measured 21-30 HU, and 28% (98/346) measured 31-39 HU. CONCLUSION. Incidental small homogeneous renal masses measuring 21-39 HU at portal venous phase CT are common and highly likely benign. CLINICAL IMPACT. The change in attenuation threshold signifying the need for additional imaging from greater than 20 HU to greater than 30 HU proposed by the Bosniak classification version 2019 is supported.


Social function of persons with schizophrenia.
1. The social function needs of persons with schizophrenia are similar to those of all individuals and include typical social roles, integration and contacts, and intimacy and sexual function. 2. Social function is essential to QOL, and aspects of social function are determinants of mental health and mental health outcomes. 3. Although intimacy and sexual function is found to be an important aspect of social function and QOL, health care workers neglect to discuss these issues with patients with schizophrenia. 4. Education, support, counseling, adequate transportation, safe environments, and treatment plans that include appropriate activities are important treatment interventions.


Visualising trends in dentition to lip mouth morphology using geometric morphometrics.
Linear measurements taken from bony landmarks are often utilised in facial approximation (FA) to estimate and plan the placement of overlying soft tissue features. This process similarly guides craniofacial superimposition (CFS) practices. Knowledge of how hard and soft tissue features spatially relate around the mouth region is, however, limited. Geometric morphometric techniques have thus been used to investigate size and shape variation in dentition-to-lip mouth morphology in a South African population. Twenty landmarks (twelve dentition, eight lips) were digitised, using cone-beam CT images of the anterior craniofacial complex in a Frankfurt/Frankfort position, for 147 individuals aged between 20 and 75 years. Principal Component Analysis and Canonical Variate Analysis established that much shape variation exists. A two-way ANOVA identified significant (p < 0.0001) population and sex variation with mouth shape. Black individuals presented with thicker lips, with the oral fissure aligning closely to the dental occlusion. Oral fissure position for white individuals corresponded to the inferior one-quarter (females) or one-sixth (males) of the maxillary central incisor crowns. Males presented larger dimensions than females, but females had a greater lip-to-teeth height ratio than their male counterparts. A pooled within-group regression analysis assessed the effect of age on the dentition and lips and found that it had a significant (p < 0.0001) impact on mouth shape. Ageing was associated with a reduced lip and teeth height, increased mouth width, and a lowered oral fissure and cheilion placement. The generated mean shape data, with metric guides, offer a visual and numerical guide that builds on existing FA and CFS standards, enhancing our understanding of hard and soft tissue relationships.


Is the front passenger seat always the "death seat"? An application of a hierarchical ordered probit model for occupant injury severity.
Although many studies have investigated the correlations between injury severities and seat positions, few researchers explored the correlates of injury severities (e.g., seat positions) within a crash that results in multiple occupant injuries. Therefore, we examine the injury correlates within and between crashes, and study the correlations between seat positions and occupant injury severity by constructing a hierarchical ordered probit model. A total of 20,327 occupant injuries in 16,405 motor vehicle crashes in South Australia (2012 - 2016) are used. The results of this study indicate that the rear left passenger seat is associated with a 7.66% higher chance of getting injured (including moderate and severe injury), and the front left passenger seat is associated with a 2.94% higher chance of getting injured compared with the driver seat. Besides, the higher injury chances for other passenger seats including the rear right and rear middle seats are 4.97% and 4.74%, respectively, compared with the driver seat. Thus, this study offers passengers insightful suggestions about how to protect themselves by choosing the right passenger seat in a vehicle.


Effects of C-reactive protein on K(+) channel interaction protein 2 in cardiomyocytes.
Several studies have found that C-reactive protein (CRP) was associated with QTc interval prolongation and ventricular arrhythmia. However, little is known about the mechanisms involved. K(+) channel interaction protein 2 (KChIP2) is a necessary subunit for the formation of transient outward potassium current (Ito.f) which plays a critical role in early repolarization and QTc interval of heart. In this study, we aimed to evaluate the effects of CRP on KChIP2 and Ito.f in cardiomyocytes and to explore the potential mechanism. The neonatal mice ventricular cardiomyocytes were cultured and treated with CRP at different concentrations. The expression of KChIP2 was detected by real time quantitative PCR and Western blot. In addition, Ito.f current density was evaluated by whole cell patch clamp techniques. Our results showed that CRP significantly decreased the mRNA and protein expression of KChIP2 in time and doses dependent manners (P < 0.05), and also reduced the current density of Ito.f (P < 0.05). In addition, CRP increased the expression of NF-κB and decreased IκBα expression without significant influence on the expression of ERK1/2 and JNK. Meanwhile, the NF-κB inhibitor PDTC significantly attenuated the effects of CRP on KChIP2 and Ito.f current density. In conclusion, CRP could significantly down-regulate KChIP2 expression and reduce current density of Ito.f partly through NF-κB pathway, suggesting that CRP may directly or indirectly influence QTc interval and arrhythmia via influencing KChIP2 expression and Ito.f current density of cardiomyocytes.


Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease.
Hypertrophic pachymeningitis (HP) is a rare disorder that causes thickening of the dura mater. Inflammatory lesions may be located in the cerebral or spinal dura mater or, less frequently, in both locations simultaneously. Numerous clinico-pathological entities cause thickening of the pachymeninges. Indeed, HP is a potential manifestation of many different diseases, but the diagnosis often remains uncertain. Cases in which the pachymeningitis has no known aetiology are termed "idiopathic" HP (IHP). Recently, it has been suggested that IgG4-related disease represents a subset of cases previously diagnosed as idiopathic hypertrophic pachymeningitis. Little is known regarding the pathogenic events of IHP. In a general theory, the inflammatory infiltrate, mainly consisting of B and T lymphocytes, activates fibroblasts and induces collagen deposition, leading to tissue hypertrophy and increased dural thickness. Clinical manifestations of IHP depend upon the location of the inflammatory lesions and compression of the adjacent nervous structures. Three central pathological features are lymphoplasmacytic infiltration, obliterative phlebitis, and storiform fibrosis. MRI is the examination of choice for the preliminary diagnosis of IHP. Histopathological examination of a biopsy specimen of the dura mater would finally confirm the diagnosis. The differential diagnosis for HP is broad and includes infections, autoimmune disorders, and neoplasia. Currently, there is no consensus about treatment for patients with IHP. There is a preference for glucocorticoid treatment on diagnosis followed by the addition of other immunosuppressive agents in the event of a recurrence. Rituximab is used in patients who did not respond to glucocorticoids or to conventional steroid-sparing agents.


Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.
Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.


Correlates of suicide among home health care utilizers who died by suicide and community controls.
Home health care patients often have several late-life risk factors for suicide and constitute a high risk group for suicidal behaviors. In this study, we examined the characteristics of 14 older adult home health care utilizers who died by suicide and four community controls who used similar services. Both groups of home health care utilizers had multiple health problems and, with one exception, all were functionally impaired. Descriptive comparison suggests that suicide decedents were more likely than their counterparts to suffer from depressed mood, suicidal ideation, prior suicide attempt(s), alcohol dependence, chronic pain, strained family relationships, lack of social support, and financial difficulties. Identifying suicide risk factors that place older adult home health care utilizers at particularly high risk for suicidal behaviors within this population will further help target suicide preventive interventions by home care providers.


Evaluation of decision-making in the treatment of acetabular fractures.
Treatment of acetabular fractures is challenging and risky, especially when surgery is performed. Yet, stability and congruity of the hip joint need to be achieved to ensure early mobilization, painlessness, and good function. Therefore, coming up with an accurate decision, whether surgical treatment is indicated or not, is the key to successful therapy. Data from the German pelvic Trauma Registry (n = 4213) was evaluated retrospectively, especially regarding predictors for surgery. Furthermore, a logistic regression model with surgical treatment as the dependent variable was established. In total, 25.8% of all registered patients suffered from an acetabular fracture and 61.9% of them underwent surgery. The fracture classification is important for the indication of surgical therapy. Anterior wall fractures were treated surgically in 10.2%, and posterior column plus posterior wall fractures were operated on in 90.2%. Also, larger fracture gaps were treated surgically more often than fractures with smaller gaps (>3 mm 84.4%, <1 mm 20%). In total, 51.4% of women and 66.0% of men underwent surgery. Apart from the injury severity score (ISS), factors that characterize the overall picture of the injury were of no importance for the indication of a surgical therapy (isolated pelvic fracture: 62.0%, polytrauma: 58.8%). The most frequent reason for non-operative treatment was 'minimal displacement' in 42.2%. Besides fracture classification and fracture characteristics, no factors characterizing the overall injury, except for the ISS, and unexpectedly gender, are important for making a treatment decision. Further studies are needed to determine the relevance of these factors, and whether they should be used for the decision-making process, in particular surgeons with less experience in pelvic surgery, can orient themselves to.


A processing approach to the working memory/long-term memory distinction: evidence from the levels-of-processing span task.
Recent theories suggest that performance on working memory (WM) tasks involves retrieval from long-term memory (LTM). To examine whether WM and LTM tests have common principles, Craik and Tulving's (1975) levels-of-processing paradigm, which is known to affect LTM, was administered as a WM task: Participants made uppercase, rhyme, or category-membership judgments about words, and immediate recall of the words was required after every 3 or 8 processing judgments. In Experiment 1, immediate recall did not demonstrate a levels-of-processing effect, but a subsequent LTM test (delayed recognition) of the same words did show a benefit of deeper processing. Experiment 2 showed that surprise immediate recall of 8-item lists did demonstrate a levels-of-processing effect, however. A processing account of the conditions in which levels-of-processing effects are and are not found in WM tasks was advanced, suggesting that the extent to which levels-of-processing effects are similar between WM and LTM tests largely depends on the amount of disruption to active maintenance processes.


Doxycycline alters the expression of inflammatory and immune-related cytokines and chemokines in human endometrial cells: implication in irregular uterine bleeding.
Increased production of pro-inflammatory mediators is considered central in the manifestation of events leading to irregular uterine bleeding in progestin-only contraceptive users. Evidence suggests that in addition to its antimicrobial property, doxycycline (Dox) acts as an anti-inflammatory agent mainly through the suppression of pro-inflammatory mediators. We tested this hypothesis in the endometrial environment using an in vitro model consisting of isolated human endometrial glandular epithelial and stromal cells and a human endometrial surface (HES) epithelial cell line cultured under defined conditions. We found that Dox at doses ranging from 1 to 100 microg/ml had a limited growth-inhibitory effect on these cells, whereas Dox in a dose-dependent manner inhibited the production of tumour necrosis factor-alpha (TNF-alpha). Using multiplex cytokine/chemokine protein analysis to test a broader range of Dox activity, we found that Dox at 25 microg/ml either alone or in the presence of 17beta-estradiol (E2), medroxyprogesterone acetate (MPA) and E2+MPA (10(-8) M) as well as TNF-alpha (25 ng/ml), representing the endometrial environment exposed to contraceptives as well as inflammatory conditions, respectively, altered the production of multiple cytokines and chemokines as compared with untreated controls. These actions of Dox occurred in cell-, ovarian steroid- and cytokine/chemokine-dependent manners. Although Dox reduced the regulatory action of steroids on the production of these cytokines/chemokines, it was less effective on TNF-alpha-treated cells. The results support the hypothesis that Dox, by modulating the endometrial expression of multiple inflammatory-related cytokines/chemokines in a cell- and cytokine/chemokine-dependent manner, may have a therapeutic potential in patients experiencing irregular uterine bleeding, in particular in progestin-dominant contraceptive users.


[3H]Flunitrazepam binding to recombinant alpha1beta2gamma2S GABAA receptors stably expressed in HEK 293 cells.
The interaction of selected compounds with the binding of the benzodiazepine [3H]flunitrazepam to membranes isolated from human embryonic kidney (HEK) 293 cells, stably transfected with the aI( 2 2S subtype of GABAA receptors, was studied. This subtype of GABAA receptors is the most common type of GABAA receptor found in the brain, and benzodiazepines are drugs known to enhance the effects of the inhibitory neurotransmitter gamma-amino butyric acid (GABA) by binding to the benzodiazepine binding sites which are part of the GABAA receptor complex. Scatchard analysis of binding data revealed the existence of a single type of binding site for [3H]flunitrazepam. GABA and thiopental enhanced, while the antagonist of central benzodiazepine binding sites--flumazenil, benzodiazepines such as clonazepam, flunitrazepam and diazepam, and the triazolopyridazine CI 218,872--displaced with nanomolar potency the binding of [3H]flunitrazepam. A partial displacement was obtained with the antagonist of the peripheral benzodiazepine binding sites--PK 11195--and with the neurosteroid dehydroepiandrosterone sulfate. The potency of drugs to enhance or inhibit [3H]flunitrazepam binding mainly corresponded to that observed for the modulation of the binding of [3H]flunitrazepam to the native type 1 benzodiazepine binding sites. This, as well as a high density of expressed binding sites, makes the cell line under study a very reliable and economical model for the testing of effects of different compounds at the GABAA receptor.


The relationship between adherence and liver metastatic ability in murine mastocytoma cell line.
P815 murine mastocytoma cells were separated to plastic-adherent and -nonadherent cell populations by repetitive in vitro selections. Their abilities of experimental and spontaneous metastases were investigated in the syngeneic DBA/2 mice. While the plastic-adherent populations were found to be liver-metastatic, the plastic-nonadherent populations were liver-nonmetastatic. The inability of plastic-nonadherent P815 cells to metastasize to the liver did not mean that these cells were not tumorigeneic because they could metastasize to tissues and/or organs other than the liver. Hence it could be looked as inability for liver specific metastasis resulted from, or related to, the loss of plastic adhesiveness. By limiting dilution of plastic-adherent and -nonadherent P815 cells, two series of well comparable P815 clones were established: (1) plastic-adherent, liver-metastatic clone and (2) plastic-nonadherent, liver-nonmetastatic one. Since these two series of P815 clone are originated from a common parent line, they might be valuable in the study of the molecular mechanisms of liver specific metastasis and of the relations between liver metastasis and cell adhesiveness.


Field efficacy assessment of a vaccine against Rhipicephalus (Boophilus) australis in New-Caledonia.
Pure European bovine breeding is compromised in South Pacific (i.e. Australia, New Caledonia) due to the impact of acaricide-resistant Rhipicephalus (Boophilus) australis ticks. Farmers need new solutions to sustainably maintain their activity. An integrated tick control program has been applied for 2 years in herds of European breeds (i.e. Charolais and Limousine cattle breeds) in New Caledonia. A field trial including the use of a vaccine based on a local Bm86 antigen, agropastoral measures and a chemical control of the tick was conducted to assess the possibility to reduce the number of acaricidal treatments. Nine farms including 1400 animals were monitored from July 2017 to June 2020. The year mid2017-mid2018 was the year of initial monitoring in order to get control data related to tick infestation during the seasons and to the number of treatments per herd. Vaccinations began between September and December 2018. Results obtained from mid2019 to mid2020 were then compared to the initial period (mid2017-mid2018) to assess the benefits of the vaccine. The average annual number of acaricide treatments decreased significantly from 7.44 before vaccination to 4.45 during mid2019-mid2020 (p = 0.026). Infestation scores, assessed by tick counts when farmers grouped the cattle to apply acaricides, showed a constant and low infestation level. Nevertheless, farmers were willing to tolerate slightly higher tick loads on vaccinated cattle with less acaricidal treatments compared to unvaccinated and frequently treated cattle. Local cutaneous reactions were recorded at the injection site with 46.6% of all injections evolving into nodules and 1% of injections giving depilation or abscesses. At the end of the trial, all the breeders wish to continue the vaccination and consider that it is now possible to serenely maintain their breed.


Making sense of ... the Sengstaken tube.
Oesophageal haemhorrage is a life-threatening condition, but it can be stemmed by the use of the Sengstaken tube. Patricia McCaffrey explains the technique for insertion and the need to monitor the patient.