[Glass fibre HEPA filters. II. Communication: Microbiological and physico-chemical researchs on used and unusued, hydrophilic and hydrophobic filter materials in an air conditioning plant (author's transl)].
Hydrophobic and hydrophilic, used and unused HEPA filters from various manufacturers, inoculated with vegetative bacteria, bacterial and fungal spores, were exposed to clean outside air for up to 17 weeks in an air conditioning plant. With relative humidities up to 60%, an increase in germ count could not be found. The rate of killing the micro-organisms inoculated were different and were generally higher on used filters. The low water content of the filter material was apparently not sufficient for microbial growth. In addition, the increase in electric conductivity and reduction of pH value resulting from deposition of substances from the outside air with an acid reaction ascertained in the aqueous filter extracts had a negative effect on the living conditions of the microorganisms.


3D virtual reality and selective vascular control for laparoscopic left hepatic lobectomy.
Careful control of haemostasis is particularly important in laparoscopic hepatic surgery, since a bloodless operative field results in safer and smoother procedures. A selective vascular control for a left lateral segmentectomy may be facilitated by the use of three-dimensional (3D) virtual reality. A 67-year-old male patient presenting with a 3.5-cm hepatocellular carcinoma (HCC) located between segment II and III of the liver was referred for hepatic resection. Transplant was contraindicated due to previous head and neck cancer surgery. Preoperative 3D reconstruction was used for preoperative planning and allowed a virtual resection to be done as well as peroperative simulation. Five ports were used. The first step was primary control of the hepatic pedicle. 3D virtual-reality reconstruction demonstrated the position of the tumor in the segment and regarding the vessels. The left hepatic artery and the portal vein were successively dissected and controlled. The real anatomy was compared to the virtual-reality reconstruction. Both demonstrated the same anatomy. Vascular section was completed and this resulted in a typical color change of the left lateral segment as well as a small decrease in size. The bisegmentectomy was performed using harmonic dissectors (Autosonix(R), Tyco Healthcare), bipolar cautery, clips, and application of Endo GIA vascular staples (Tyco Healthcare) on the portal pedicles. The procedure was completed following isolation and control of the left hepatic vein. After section, the specimen was placed in a bag and extracted following enlargement of the camera port. Follow-up was uneventful and there was no elevation of hepatic enzymes or postoperative ascites. The patient left the hospital on the fifth postoperative day. 3D reconstruction allowed the procedure to be simulated preoperatively. This facilitated the intraoperative identification of the vascular anatomy and the control of the left lateral segment arteries and veins, thus preventing intraoperative bleeding. The use of this approach in preoperative planning is recommended.


Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer.
TGF-β1, β2 and β3 bind a common receptor to exert vastly diverse effects in cancer, supporting either tumor progression by favoring metastases and inhibiting anti-tumor immunity, or tumor suppression by inhibiting malignant cell proliferation. Global TGF-β inhibition thus bears the risk of undesired tumor-promoting effects. We show that selective blockade of TGF-β1 production by Tregs with antibodies against GARP:TGF-β1 complexes induces regressions of mouse tumors otherwise resistant to anti-PD-1 immunotherapy. Effects of combined GARP:TGF-β1/PD-1 blockade are immune-mediated, do not require FcγR-dependent functions and increase effector functions of anti-tumor CD8+ T cells without augmenting immune cell infiltration or depleting Tregs within tumors. We find GARP-expressing Tregs and evidence that they produce TGF-β1 in one third of human melanoma metastases. Our results suggest that anti-GARP:TGF-β1 mAbs, by selectively blocking a single TGF-β isoform emanating from a restricted cellular source exerting tumor-promoting activity, may overcome resistance to PD-1/PD-L1 blockade in patients with cancer.


Spurious hypercalcitoninemia and heterophilic antibodies in patients with thyroid nodules.
The purpose of our study was to examine the prevalence of significant heterophilic antibody (HAb) interferences in serum calcitonin measurement in a large cohort of patients with thyroid nodules. Enrolled in the study were 378 patients with thyroid nodules shown not to have medullary thyroid carcinoma (MTC) after extensive diagnostic workup. Serum calcitonin measurement was performed before and after incubating each serum sample in heterophilic-blocking tubes (HBTs) and the differences were calculated. Samples showing an absolute percentage difference greater than 3 SD from the mean percentage difference were considered as affected by heterophilic antibody interference. Five of 378 patients (1.3%) with HAb interferences were identified, 4 with clinically relevant false-positive calcitonin results. A false-positive calcitonin result due to HAb interference occurs more frequently than MTC (1.3% vs 0%) in our patient series. A serum pretreatment in HBTs should be considered when increased serum calcitonin levels are found in a patient with a thyroid nodule to prevent unwarranted investigations or therapies.


Comparison between two methods of bioelectrical impedance analyses for accuracy in measuring abdominal visceral fat area.
To compare the accuracy of abdominal visceral fat area (VFA) measurements between abdominal dual bioelectrical impedance analysis (BIA) and whole-body BIA referenced to computed tomography (CT) measures. Abdominal VFAs were measured in 102 individuals: 59 men and 43 women with a mean age of 44.2 ± 16.3 years (range 21 - 76), body mass index 23.9 ± 7.8 kg/m(2) (range 18 - 35) using a DUALSCAN HDS-2000 machine (dual abdominal BIA) and an InBody720 machine (whole-body BIA). The VFA values from each machine were compared with those from CT under various conditions. Mean abdominal VFAs were 116 ± 69 cm(2) by CT, 89 ± 47 cm(2) by dual abdominal BIA, and 84 ± 33 cm(2) by whole-body BIA. The former measure showed a higher correlation with the CT measure than the latter (r=0.89 vs. r=0.64, P<0.001). Both BIA methods tended to underestimate abdominal VFAs compared with CT scans when CT VFA was not small. The dual abdominal BIA had less bias than the whole-body BIA in the assessment of VFAs. The whole-body BIA was affected by subcutaneous fat area. Dual BIA was more accurate in assessing abdominal VFA than whole-body BIA.


Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners.
Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.


CRISPR-PIN: Modifying gene position in the nucleus via dCas9-mediated tethering.
Spatial organization of DNA within the nucleus is important for controlling DNA replication and repair, genetic recombination, and gene expression. Here, we present CRISPR-PIN, a CRISPR/dCas9-based tool that allows control of gene Position in the Nucleus for the yeast Saccharomyces cerevisiae. This approach utilizes a cohesin-dockerin interaction between dCas9 and a perinuclear protein. In doing so, we demonstrate that a single gRNA can enable programmable interaction of nuclear DNA with the nuclear periphery. We demonstrate the utility of this approach for two applications: the controlled segregation of an acentric plasmid and the re-localization of five endogenous loci. In both cases, we obtain results on par with prior reports using traditional, more cumbersome genetic systems. Thus, CRISPR-PIN offers the opportunity for future studies of chromosome biology and gene localization.


Euchromatin megabase cleavages and conjoint apoptotic-autophagic death expression with nucleolar ball-and-socket joint dislocations in human Chang liver cells arrested in S-phase by etoposide.
Etoposide induced a megabase (Mb) fragmentation pattern identical with that from genomic digestion by NotI restriction endonuclease which specifically cleaves CpG islands in euchromatin domains. Redigestion by NotI produced no change, suggesting cleavage in the same or closely related sites in euchromatin domains. Preferential euchromatin cleavage was further suggested by harvested metaphase chromosomes showing self-inflicted resolution of light G-bandings (R-bandings), the euchromatin domains. Autodegeneration following Mb euchromatin fragmentations was shown by their degradation into 200 bp ladders, and expressions of apoptotic and "non-apoptotic" active death morphologies that were also seen conjointly in the same cell. The endstage further showed heterochromatin masses anchored to the nucleolus by novel ball-and-socket joints where dislocations occurred with nuclear leakage.


Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission.
Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission. Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts. We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant. Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.


Cytochemical demonstration of estrogen binding sites in breast cancer by estradiol covalently linked to horseradish peroxidase.
17 beta-Estradiol-6-carboxymethyloxime was covalently linked to horseradish peroxidase for the cytochemical demonstration of estrogen binding sites in breast cancer tissue. The affinity of the 17 beta-estradiol-horseradish peroxidase (E2-HRP) conjugate for the estrogen receptor in a human myometrial cytosol preparation was reduced by a factor of about 16 relative to that of 17 beta-estradiol. The estradiol concentration of the E2-HRP conjugate used in the incubations was in the range 2 X 10(-9) -1 X 10(-7) mol/l which, when the reduced affinity of the conjugate is taken into account, corresponds to 1 X 10(-10) -7 X 10(-9) mol/l unbound estradiol. The cytochemical reaction was carried out on cytofuge preparations of cell suspensions of breast cancer tissue. The intensity of the cytochemical reaction was microscopically evaluated by scoring. The results were analyzed in a plot allowing the calculation of an apparent score-max and an apparent Kd value. The reaction intensity was reduced to 20-25% of the control level by a 20-fold excess of 17 beta-estradiol. The cytochemical results correlated positively with the content of estrogen receptors in the cytosol as measured by a validated radioligand method.


Measurement of dark adaptometry during ISCEV standard flash electroretinography.
Dark adaptometry (DA) is a sensitive test for diagnosis of retinal disease. Patients requiring flash electroretinograms (ERGs) benefit from DA for proper diagnosis. Our purpose was to develop a DA test to be administered during the 20-min dark adaptation period of the flash ERG ( www.iscev.org ) using alternating red and blue stimuli to bias responses in favor of cones (red) and rods (blue). An ERG Ganzfeld was used to measure DA in 21 normal subjects and 21 patients with retinal disease. Subjects underwent 75 s of preadaptation followed by 20 min of DA using an adaptive staircase to detect alternating flashes of red and blue light. Normative red and blue DA was compared to patients at the 10-min midpoint and 20-min final threshold. At 15 min, normals and patients showed asymptotic plateaus; hence, final thresholds were achieved within 15 min for parameters of this study. In RP and allied conditions (n = 11), 100% showed significantly elevated blue DA thresholds (> 2SD above normal) at 10 and 20 min. In cone diseases, 80% showed abnormal red DA at 10 min and 30% at 20 min, indicating that delayed adaptation is more typical of cone disease. Two-color DA is expediently measured during the DA phase of ERGs providing clinical data which separate rod and cone dysfunction critical for accurate diagnosis of various retinal diseases. It provides an additional benchmark for monitoring function over time and invaluable guidance for patients functioning in dimly lit settings.


Differential diagnosis between amyotrophic lateral sclerosis and spinal muscular atrophy by skin involvement.
Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) might be clinical variants caused by the same etiology, or different diseases altogether. We studied the skin in 12 patients with ALS and 7 patients with SMA. The "delayed return phenomenon" (DRP) was observed only in ALS patients. On light microscopy, collagen bundles in ALS dermis were seen to be less numerous, thinner and more loosely woven than in SMA. Electron microscopy revealed that in ALS (1) collagen fibers became thinner as the disease lasted longer, and (2) collagen bundles were separated by much more amorphous material. These findings were not observed in SMA. Our observations show that ALS may be distinguished from SMA by the presence of abnormal dermal collagen. Therefore, we suggest that comparable clinical and pathological skin analysis is the most important diagnostic tool in differentiating between ALS and SMA.


De Winter electrocardiogram pattern due to type A aortic dissection: a case report.
De Winter electrocardiograph (ECG) pattern is an atypical presentation of acute myocardial infarction (AMI) due to severe stenosis of the left anterior descending (LAD). Complications of acute aortic dissection (AD) in the setting of acute myocardial infarction (AMI) with de Winter sign are relatively rare and physicians may easily miss the diagnosis of AD. We report a case of patient with acute chest pain and de Winter ECG pattern due to AD involving the left main coronary artery (LM), LAD and left circumflex artery (LCX). A 57-year-old male patient was initially diagnosed with AMI and then the diagnosis of acute AD was supported by transthoracic echocardiograph (TTE). After two stents were implanted respectively into the proximal LM-LAD and LM-LCX, he recovered from cardiogenic shock. Two months later, the patient underwent the surgery of ascending aorta replacement. After the surgery, there was no obvious chest discomfort during follow-up. When an ECG shows a "de Winter pattern", we should also consider the possibility of AD which result in LAD occlusion. TTE is a useful tool in screening for AD. Further research is needed to prove that percutaneous coronary intervention (PCI) may be a useful treatment strategy in the case of AD leading to severe LAD occlusion and unstable hemodynamics when there's no condition to perform aortic replacement surgery immediately.


M2 muscarinic receptors mediate pressor responses to cholinergic agonists in the ventrolateral medullary pressor area.
Microinjections of cholinergic agonists into the ventrolateral medullary pressor area (VLPA) evoke increase in blood pressure (BP) and heart rate (HR). Recently two major subtypes of muscarinic receptors (M1 and M2) have been identified. This investigation was designed to study the role of these muscarinic receptor subtypes in pressor responses of cholinergic agonists in the VLPA. Male Wistar rats were anesthetized with pentobarbital or decerebrated at mid-collicular level. The rats were artificially ventilated and BP and HR were recorded. Ventral medulla was exposed and the VLPA identified bilaterally by microinjections of L-glutamate. Microinjections of cis-methyldioxolane (CD, a specific agonist of M2 receptors) in the doses of 0.004-4 nanomol (nmol)/site into the VLPA evoked an increase in BP (13-56 mm Hg) and HR (7-24 bpm) which lasted for 10-50 min. Intravenous injections of the same doses of this agent failed to evoke a response. AFDX-116 (a specific M2 muscarinic receptor antagonist) microinjected into the VLPA (0.2-1.6 nmol-/site) evoked depressor responses (6-20 mm Hg). Microinjections of this agent into the VLPA prevented the pressor responses to subsequent microinjections of CD at the same sites, indicating that AFDX-116 blocked M2 receptors. AFDX-116 rendered neurons in the VLPA unresponsive to L-glutamate but this effect lasted for 30-40 min while the hypotensive and M2 receptor blocking effect lasted for 60-150 min. McN-A343 (a specific agonist for M1 receptors) or pirenzepine (PZ, a specific antagonist of M1 receptors) injected into the VLPA (0.4-4 nmol/site) failed to evoke any response.(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship between nonalcoholic fatty liver disease and hyperandrogenemia in adolescents with polycystic ovary syndrome.
Nonalcoholic fatty liver disease (NAFLD) is common in adults with polycystic ovary syndrome (PCOS), and several studies on adults have investigated its influencing factors. However, factors associated with NAFLD in adolescents with PCOS remain unknown. This study aimed to investigate the presence of NAFLD in adolescents with PCOS using the noninvasive methods of vibration-controlled transient elastography (VCTE) and ultrasonography (USG), along with assessing NAFLD-related metabolic and hormonal risk factors. This study included patients aged 12-18 years who were diagnosed with PCOS according to the Rotterdam criteria. The control group included young women with similar age and body mass index (BMI) z scores, who had menstruated regularly for more than 2 years. Patients with PCOS were divided into hyperandrogenemia and nonhyperandrogenemia groups based on serum androgen level. USG was performed on all patients to evaluate the presence of hepatic steatosis. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed using VCTE (Fibroscan). Clinical, laboratory, and radiological data were compared between groups. This study included 124 adolescent girls aged 12-18 years (61 with PCOS, 63 controls). BMI z scores were similar between groups. Waist circumference and total cholesterol, triglyceride, and alanine aminotransferase levels were higher in the PCOS versus the control group. The presence of hepatic steatosis on USG was similar between groups. However, the rate of hepatic steatosis on USG was higher in patients with hyperandrogenic PCOS (P=0.01). LSM and CAP measurements were similar between groups. No increase in prevalence of NAFLD was observed among adolescents with PCOS. However, hyperandrogenemia is a risk factor for NAFLD. Therefore, adolescents with PCOS and elevated androgen level should be screened for NAFLD.


Hystological analysis of ovarian development of the characiform Oligosarcus hepsetus (Cuvier, 1829) in a Brazilian reservoir.
A histological analysis was performed of the ovarian development of Oligosarcus hepsetus (Cuvier, 1829), a medium-sized carnivorous Characiform species in the Lajes reservoir, Brazil. A total of 125 fishes, collected monthly between April 2001 and June 2002 were examined by routine macroscopic and histological techniques. Eight phases of the oocyte development were described, and 4 stages and 4 substages of gonadal development were proposed. Spawning in reservoirs, similarly to that in rivers, is in batches, which favors juvenile survival and suggests that the impoundment of this area did not influence the reproductive strategy of this very successful species in a dammed environment.


Abnormalities of emotional awareness and perception in patients with obsessive-compulsive disorder.
Emotional awareness deficit may play a critical role in the production and maintenance of obsessive-compulsive symptoms and social dysfunction in patients with obsessive-compulsive disorder (OCD). The aim of this study was to investigate characteristics of emotional awareness such as empathy and alexithymia in OCD patients. In addition, we examined whether impaired emotional awareness measured by self-assessment questionnaires was associated with emotional facial recognition ability in OCD patients. Study participants included 107 patients with OCD and 130 healthy age- and sex-matched volunteers. The Interpersonal Reactivity Index (IRI) and Toronto Alexithymia Scale-20 were applied as measures of empathy and alexithymia. A subset of 56 patients with OCD additionally performed the emotional perception task of face expression. Patients with OCD scored significantly lower for perspective taking, and significantly higher for personal distress of IRI, and significantly higher for alexithymia compared to normal controls. Impaired emotional awareness such as lower perspective taking and fantasy seeking had a perception bias towards disgust in response to ambiguous facial expressions in OCD patients. The OCD group consisted of patients in different stages of the illness and with different degrees of severity. OCD involves the impairment of emotional awareness and perception and it may relate to social dysfunction and to impairments in the ability to shift naturally from obsessive thoughts to other thoughts in response to social situations in patients with OCD.


Ultra-fast separation of infectious disease-related small DNA molecules by single- and multi-channel microchip electrophoresis.
An ultra-fast and precise microchip electrophoresis (ME) method was developed for the separation of infectious disease-related small DNA molecules. As a model of infectious disease-related small DNA molecules, the spike glycoprotein (S) gene of the Feline infectious peritonitis (FIP) virus was amplified using reverse transcript polymerase chain reaction. The amplified product of the FIP virus (223-bp) was analyzed within 10s by single-channel ME under a sieving gel of 0.3% poly(ethylene oxide) (Mr=8,000,000) in 1x TBE buffer (pH 8.33) and a short effective channel length of 1.3 cm with a programmed step electric field strength (PSEFS) condition as follows: 470.6 V/cm for 9 s, 294.1 V/cm 1.5 s, and 470.6 V/cm for 9.5 s. The single-channel ME/PSEFS method was 50 times faster than that obtained with conventional slab gel electrophoresis. When the single-channel ME method was applied to a multi-channel ME for high-throughput screening, the precision of migration time and peak area showed standard deviations of less than 1.0% without any loss of resolving power. The ME assay technique provides a simple, precise and accurate method for ultra-fast analysis of infectious disease-related DNA under 400-bp.


Conformations of dehydrophenylalanine containing peptides: nmr studies of an acyclic hexapeptide with two delta Z-Phe residues.
The conformation of an acyclic dehydrophenylalanine (delta Z-Phe) containing hexapeptide, Boc-Phe-delta Z-Phe-Val-Phe-delta Z-Phe-Val-OMe, has been investigated in CDCl3 and (CD3)2SO by 270-MHz 1H-nmr. Studies of NH group solvent accessibility and observation of interresidue nuclear Overhauser effects (NOEs) suggest a significant solvent-dependent conformational variability. In CDCl3, a population of folded helical conformations is supported by the inaccessibility to solvent of the NH groups of residues 3-6 and the detection of several NiH----Ni + 1H NOEs. Evidence is also obtained for conformational heterogeneity from the detection of some Ci alpha H----Ni + 1H NOEs characteristic of extended strands. In (CD3)2SO, the peptide largely favors an extended conformation, characterized by five solvent-exposed NH groups and successive Ci alpha H----Ni + 1H NOEs for the L-residues and Ci beta H----Ni + 1H NOEs for the delta Z-Phe residues. The results suggest that delta Z-Phe residues do not provide compelling conformational constraints.


Generating MHC Class II+/Ii- phenotype after adenoviral delivery of both an expressible gene for MHC Class II inducer and an antisense Ii-RNA construct in tumor cells.
Tumor cells engineered by gene transduction to be MHC Class II+/Ii- are novel APCs capable of presenting endogenous tumor antigen epitopes to activate T helper cells. The MHC Class II+/Ii- tumor cell phenotype is created by transfecting genes for either CIITA or IFN-gamma, and inhibiting induced Ii mRNA by an Ii reverse gene construct (Ii-RGC). Adenoviral vectors are preferred for the delivery of such genes because of high infection efficiency and ubiquity of the adenoviral receptor on many cell types and tumors. Here we show that at 5 MOI (multiplicity of infection), recombinant adenoviruses with CIITA or IFN-gamma genes converted virtually all MC-38 colon adenocarcinoma cells and Renca renal carcinoma cells in culture to MHC Class II+/Ii+ cells. A single recombinant adenovirus with both genes for IFN-gamma and Ii-RGC (rAV/IFN-gamma/Ii-RGC) efficiently induced the MHC Class II+/Ii- phenotype. Injection of tumor nodules with rAV/Ii-RGC and rAV/CIITA/IFN-gamma combined with a suboptimal dose of rAV/IL-2 induced a potent antitumor immune response. The methods are adaptable for producing enhanced genetic vaccines, attenuated virus vaccines (eg, vaccinia), and ex vivo cell-based vaccines (dendritic and tumor cells).


Tyrosine kinase activity of a Ca2+/calmodulin-dependent protein kinase II catalytic fragment.
A 30-kDa fragment of Ca(2+)/calmodulin-dependent protein kinase II (30K-CaMKII) is a constitutively active protein Ser/Thr kinase devoid of autophosphorylation activity. We have produced a chimeric enzyme of 30K-CaMKII (designated CX(40)-30K-CaMKII), in which the N-terminal 40 amino acids of Xenopus Ca(2+)/calmodulin-dependent protein kinase I (CX(40)) were fused to the N-terminal end of 30K-CaMKII. Although CX(40)-30K-CaMKII exhibited essentially the same substrate specificity as 30K-CaMKII, it underwent significant autophosphorylation. Surprisingly, its autophosphorylation site was found to be Tyr-18 within the N-terminal CX(40) region of the fusion protein, although it did not show any Tyr kinase activity toward exogenous substrates. Several lines of evidence suggested that the autophosphorylation occurred via an intramolecular mechanism. These data suggest that even typical Ser/Thr kinases such as 30K-CaMKII can phosphorylate Tyr residues under certain conditions. The possible mechanism of the Tyr residue autophosphorylation is discussed.


TFLUX: a general purpose program for the interpretation of radioactive tracer experiments.
TFLUX is a computer program which simulates radioactive tracer experiments using intact cells under steady-state conditions. It is designed for the naive computer user to use, providing English-like input. An example is described in which compartmentation and flux through the citric acid cycle in Dictyostelium discoideum are simulated.


Prevalence of markers of hepatitis viruses in out-patient alcoholics.
The prevalence of HCV, HBV and HAV markers was investigated in unselected patients attending an outpatient alcoholic clinic. Anti-HCV were detected in 35 (24%) of 144 patients studied, and at least one marker of HBV infection was present in 72 (50%). These results are significantly higher than in a matched control population. The presence of anti-HCV was related to previous blood transfusions and familial history of alcoholism. We conclude that alcoholics should be considered a high risk group for both HCV and HBV infection.


The alpha subunit of toluene dioxygenase from Pseudomonas putida F1 can accept electrons from reduced FerredoxinTOL but is catalytically inactive in the absence of the beta subunit.
The oxygenase component of toluene dioxygenase from Pseudomonas putida F1 is an iron-sulfur protein (ISPTOL) consisting of alpha (TodC1) and beta (TodC2) subunits. Purified TodC1 gave absorbance and electron paramagnetic resonance spectra identical to those given by purified ISPTOL. TodC1 was reduced by NADH and catalytic amounts of ReductaseTOL and FerredoxinTOL. Reduced TodC1 did not oxidize toluene, and catalysis was strictly dependent on the presence of purified TodC2.


Polysaccharides and proteins based bionanocomposites as smart packaging materials: From fabrication to food packaging applications a review.
Food industry is the biggest and rapidly growing industries all over the world. This sector consumes around 40 % of the total plastic produced worldwide as packaging material. The conventional packaging material is mainly petrochemical based. However, these petrochemical based materials impose serious concerns towards environment after its disposal as they are nondegradable. Thus, in search of an appropriate replacement for conventional plastics, biopolymers such as polysaccharides (starch, cellulose, chitosan, natural gums, etc.), proteins (gelatin, collagen, soy protein, etc.), and fatty acids find as an option but again limited by its inherent properties. Attention on the initiatives towards the development of more sustainable, useful, and biodegradable packaging materials, leading the way towards a new and revolutionary green era in the food sector. Eco-friendly packaging materials are now growing dramatically, at a pace of about 10-20 % annually. The recombination of biopolymers and nanomaterials through intercalation composite technology at the nanoscale demonstrated some mesmerizing characteristics pertaining to both biopolymer and nanomaterials such as rigidity, thermal stability, sensing and bioactive property inherent to nanomaterials as well as biopolymers properties such as flexibility, processability and biodegradability. The dramatic increase of scientific research in the last one decade in the area of bionanocomposites in food packaging had reflected its potential as a much-required and important alternative to conventional petroleum-based material. This review presents a comprehensive overview on the importance and recent advances in the field of bionanocomposite and its application in food packaging. Different methods for the fabrication of bionanocomposite are also discussed briefly. Finally, a clear perspective and future prospects of bionanocomposites in food packaging were presented.


Development of an efficient single-step freeze-drying cycle for protein formulations.
An efficient freeze-drying cycle for recombinant human interleukin-1 receptor antagonist (rhIL-1ra) formulations, which contained glycine and sucrose as excipients, was developed. Development was based on characterizing the frozen formulations by thermal analysis and by examining the effect of various lyophilization process parameters on the sublimation rate of ice. Thermal analysis showed that the metastable glass of glycine in frozen formulation could be devitrified by slowly warming the frozen product to -15 degrees C. During drying, the sublimation rate of ice was increased as a linear function of the difference between the vapor pressure of ice at the product temperature (PO) and the chamber pressure (PC). Therefore, the product temperature (Tp) was maintained as high as possible at temperatures below Tg' of the formulation, in order to maximize the PO without allowing the collapse of cake. Although various combinations of shelf temperatures and chamber pressures could be used to obtain the same Tp, the combination of higher shelf temperature and lower chamber pressure was used to maximize sublimation rate. A single-step drying cycle was developed to take advantage of these observations. The shelf temperature was set for the secondary drying and the product temperature during primary drying was maintained below Tg' by adjusting the chamber pressure. As the sublimation completed, the product temperature increased naturally to the shelf temperature for the secondary drying. This process resulted in successful drying of 1 ml of rhIL-1ra formulation to 0.4% moisture content within 6 hours.


The gluconeogenicity of fatty acids in mammals.
Although excess glucose can be readily converted to fatty acids in mammals, most textbooks state that glucose cannot be formed from fatty acids. Whilst this remains largely true, several pathways have now been discovered in mammals in which fatty acids are potentially gluconeogenic.


Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population.
Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.


Autorhythmicity of spontaneous interictal spike discharge at hippocampal penicillin foci.
Penicillin-induced epileptogenic foci in the cat hippocampus show a marked tendency for brief but periodic seizure discharges known as 'interictal spikes' (IS). Here, each IS is shown to be followed by a marked elevation and subsequent slow fall-off of the focal seizure threshold. The time constant of this process approximates the spontaneous inter-IS interval and these two parameters appear to vary in concert. The timing of the IS train is always reset by interjected ISs but not by stimuli that are subthreshold for the IS. In sum, this modulation of focal excitability does not appear to be imposed by local or projected rhythmic activity other than that initiated by the IS itself. The firing patterns of the majority of observed hippocampal single units in the vicinity of the focus show a prolonged suppression of spontaneous firing for from 2 to 10 sec or more after each IS, independent of whether the IS was spontaneous or elicited. A smaller number of units show delayed, intense activation following each IS. Both of these forms of response appear to originate from large cells in and near the pyramidal cell body layer. Assuming that these single unit data represent a sampling of pyramidal cell discharge, then the prevalence of a prolonged post-IS pause suggests that the rhythmicity of spontaneous penicillin foci derives from an inhibitory phasing of the population based paroxysmal activity. The periodic spontaneous IS discharge can be viewed, therefore, as a locally regulated, autorhythmic process impressed upon the activity of the neuronal population by the development of a functional suppression of unit activity following each IS.


[Possibilities for improving fatigue properties of interlocking screws of solid tibial nails. A mathematical model with practical conclusions].
One major problem using small diameter nails in the treatment of tibial fractures is the high rate of fatigue fractures of the locking screws. The objective of this study was to develop a mathematical model for analysis of the stress concentration factor as well as edge fibre stress. This would allow an analysis of the stress peaks caused by the thread of the screw as well as showing ways to increase the fatigue limits of the screws. The main consideration was the fact that a thread can be calculated like a relief notch used in theory of strength to relieve the strain on building materials. The transformation from one notch to multiple notches obviously reduces the stress concentration factor. To improve the fatigue limit of locking screws one has to modify the stress concentration factor or the edge fibre stress on the implant. Absence of a thread at the location where the screw contacts the nail's aperture (where the main load is transmitted to the screw and where the screw therefore usually tends to break) may double the fatigue strength and fatigue limit by avoiding the negative notch effect of the screw's thread. If this option is not possible one has to consider that the optimal threaded screw should have a minimal edge distance, a high notch radius and a minimal edge depth.


Patterns-of-failure guided biological target volume definition for head and neck cancer patients: FDG-PET and dosimetric analysis of dose escalation candidate subregions.
To identify the radio-resistant subvolumes in pretreatment FDG-PET by mapping the spatial location of the origin of tumor recurrence after IMRT for head-and-neck squamous cell cancer to the pretreatment FDG-PET/CT. Patients with local/regional recurrence after IMRT with available FDG-PET/CT and post-failure CT were included. For each patient, both pre-therapy PET/CT and recurrence CT were co-registered with the planning CT (pCT). A 4-mm radius was added to the centroid of mapped recurrence growth target volumes (rGTV's) to create recurrence nidus-volumes (NVs). The overlap between boost-tumor-volumes (BTV) representing different SUV thresholds/margins combinations and NVs was measured. Forty-seven patients were eligible. Forty-two (89.4%) had type A central high dose failure. Twenty-six (48%) of type A rGTVs were at the primary site and 28 (52%) were at the nodal site. The mean dose of type A rGTVs was 71Gy. BTV consisting of 50% of the maximum SUV plus 10mm margin was the best subvolume for dose boosting due to high coverage of primary site NVs (92.3%), low average relative volume to CTV1 (41%), and least average percent voxels outside CTV1 (19%). The majority of loco-regional recurrences originate in the regions of central-high-dose. When correlated with pretreatment FDG-PET, the majority of recurrences originated in an area that would be covered by additional 10mm margin on the volume of 50% of the maximum FDG uptake.


The ARRIVE Trial: Towards a universal recommendation of induction of labour at 39 weeks?
Both caesarean surgery and induction of labour are common practices performed in all labour wards in an attempt to reduce adverse obstetrical and neonatal outcomes. Recent evidence, notably from the ARRIVE Trial, demonstrated that elective induction at 39 weeks reduced the rate of caesarean deliveries and pregnancy-related hypertensive disorders. However, some concerns have to be addressed as the benefits of universal policies have to be weighed against the actual circumstances of their implementation, the economic impact, the number of procedures needed in order to effectively reduce complications and, above all, women's perception towards this approach at the end of pregnancy. Further research is needed to explore individual tailored strategies in order to offer a personalized prognosis to each woman, rather than a blanket application of general recommendations.


Specnuezhenide ameliorates ultraviolet-induced skin photoaging in mice by regulating the Sirtuin 3/8-Oxoguanine DNA glycosylase signal.
Ultraviolet-induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus, possesses antioxidant and anti-inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. Specnuezhenide ameliorated ultraviolet-induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and β-galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD-like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD-like receptor family pyrin domain-containing 3, gasdermin D-C1, and Caspase 1. Furthermore, the expression of 8-Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide-treated mice with photoaging. Specnuezhenide protected against ultraviolet-induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.


The gelling behavior of gellan in the presence of different sodium salts.
It is well known that metal ions have great effects on gelling behaviors of gellan aqueous systems, however, the effects of their co-ions - anions have rarely been studied. Herein, we investigated the effects of four kinds of sodium salts with different anions (NaCl, CH3COONa, Na2C2O4 and Na3C6H5O7) on gelling behaviors of gellan aqueous systems in terms of gelling temperature and gel hardness. It was found that, when [Na+] was low (20 mM), the salt with Cl- or CH3COO- favored the gelling of gellan aqueous systems, while the salt with C2O42- or C6H5O73- took adverse effects probably because C2O42- or C6H5O73- could react with divalent cations (Ca2+ and Mg2+) in gellan to form precipitates or chelates and break their interactions with gellan (salt bridges). When [Na+] was high (50 or 80 mM), all the four kinds of salts facilitated gelling due to the shielding effects of high concentrations of Na+ on the negative charges along the gellan chains, and followed the order of: Cl- > CH3COO- > C2O42- > C6H5O73-. This study demonstrates the effects of anion kind of salts on gelling behaviors of gellan aqueous systems and provides references for the application of gellan.


Conceptualization and Reporting of Context in the North American Continuing Medical Education Literature: A Scoping Review Protocol.
Within continuing medication education (CME), it has been argued that an "authentic" clinical context should be built into CME activities for knowledge to be effectively translated into clinical practice. However, although context is considered significant in the success (or lack thereof) of an intervention, there is a lack of consensus on what exactly context is. This scoping review arises from concerns surrounding the opaque, complex, and potentially problematic relationship between context and the effective design and implementation of CME interventions. In this article, we present a protocol for examining how context is discussed within the CME literature. The specific purpose of this scoping review is to summarize the breadth of existing evidence on context within the North American CME literature. The scoping review methodology will also highlight gaps in the current literature, which can inform future research endeavors.


A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.
We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.


Leaf adaptations and species boundaries in North American Cercis: implications for the evolution of dry floras.
The North American Cercis clade spans dry to mesic climates and exhibits complex morphological variation. We tested various proposed species classifications of this group and whether aspects of leaf morphology, particularly the "drip-tip" in some regional populations, are adaptive and/or linked with phylogeny. We made measurements on over 1100 herbarium specimens from throughout North America and analyzed the data with univariate and multivariate approaches. We analyzed phylogenetically DNA sequence data from nuclear ITS and three plastid regions from 40 samples, and estimated divergence times with a relaxed-clock Bayesian analysis. We used climate and geographic position data to predict the variation observed in leaf size and shape by using stepwise multiple linear regressions. Morphometric analyses yielded a pattern of continuous and often clinal character variation across North America, without correlated gaps in character states. Conversely, phylogenetic and divergence time analyses yielded distinct clades from California, the interior west, and eastern North America separated by between ~12 and 16 million years. Multiple regressions yielded highly significant correlations between leaf apex shape and precipitation of the warmest quarter. Despite a pattern of continuous morphological character variation, the long period of geographic and presumably genetic isolation warrants the delimitation of three species. Predictive modeling supports the adaptive value of acuminate apices or "drip-tips" in mesic habitats. This suggests that Cercis leaves change more rapidly than inferred from parsimony reconstruction, which has implications for the evolution of the dry floras of North America and Eurasia.


Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study.
Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.


Variation of distances from mid-urethra to the obturator foramen: an MRI study.
To estimate distances from the mid-urethra to the obturator foramina and to explore correlations between pelvic dimensions and body height. This is a secondary analysis of a parent case-control study on the mechanisms of stress urinary incontinence. We measured pelvic dimensions on magnetic resonance images of women with (cases, n = 50) and without (controls, n = 50) stress urinary incontinence. The mean distance from mid-urethra to the obturator membrane among cases is 31.8 mm (left) and 32.1 mm (right), with a range from 25.9 to 42.0 mm. There were no significant differences in these distances when comparing left with right, or cases with controls. Weak correlation was found between the urethra-to-obturator foramina distances and heights only in the case subjects. There is high variability in the distance from mid-urethra to the obturator foramina. Height should not be used as a predictor of dimensions in the lesser pelvis.


Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with moderate dyslipidemia.
This study investigated the efficacy, safety, tolerability, and pharmacokinetics of a novel cholesterol absorption inhibitor, FM-VP4, comprising disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol phosphate (DACP). In phase 1, 30 men received a single dose of 100, 200, 400, 800, 1,600, or 2,000 mg FM-VP4 or placebo. In phase 2, 100 men were treated with 100, 200, 400, or 800 mg/day of FM-VP4 or placebo for 4 weeks. The drug was well tolerated at each single or multiple dose level. After 4 weeks of treatment, low-density lipoprotein cholesterol (LDL-C) levels changed by 2.7% in the placebo group and by 2.9%, -4.2%, and -4.6% in the 100, 200, and 800 mg/day groups, respectively, which was not statistically significant. However, 400 mg/day of FM-VP4 significantly decreased LDL-C by 6.5% (p=0.02). Phase 1 showed that DACP and DASP were absorbed into plasma with a median t(max) of 12 h for both components, and clearance was slow with a mean t(1/2lambda) of 57 h. During 4 weeks of treatment, steady state was reached by approximately 8 days. This study demonstrated that up to 800 mg/day of FM-VP4 is safe and well tolerated for at least 4 weeks. Furthermore, the higher doses significantly reduced LDL-C by 7% compared with baseline or by 10% compared with placebo, with the maximum effect reached at 400 mg/day.


Ligand-exchange chromatography of amino acids on nickel-Chelex 100.
A ligand-exchange chromatographic proceudre for the selective separation of amino acids from inorganic ions is presented. It was found that the binding of amino acids to the nickel-Chelex 100 resin is pH dependent. At pH 8.5-9.1, only the basic amino acids lysine, histidine and arginine are quantitatively attached to the complex, whereas at pH 11, other amino acids with the exception of aspartic acid and glutamic acid are also bound, although not quantitatively. All of the amino acids can be eluted from the complex with 3 M ammonia solution without the displacement of nickel ions from the complex. This method can be used for the removal of the basic amino acids from solutions in the presence of inorganic ions as well as other amino acids.


An ultrasensitive method for the measurement of human leukocyte calcium: lymphocytes.
Studies of the transport and distribution of calcium in leukocytes have been severely hampered by the inability to measure accurately and reproducibly the concentration of calcium in small numbers of cells. We have applied a recent development in analytical chemistry, the graphite furnace atomic absorption spectrophotometer, to this problem. The calcium content of human blood lymphocytes was determined by both graphite furnace and conventional flame atomic absorption spectrophotometry. The linearity, sensitivity and detection limits of the two techniques were compared. For measurement of calcium, the graphite furnace sensitivity was 55 times higher in aqueous samples and 60 times higher in cell samples than the flame technique. The detection limit of the graphite furnace was 800 times lower in aqueous samples and 1500 times lower in cell samples. The enhanced sensitivity of this technique allowed us to prepare samples with 20 times fewer blood cells. We have employed this graphite furnace technique to measure lymphocyte calcium content and its relationship to the calcium concentration and proportion of serum in the suspending medium. In the absence of serum, the lymphocyte calcium content approximately doubled as the medium calcium concentration was increased from 1 mumol/l to 0.5 mmol/l. At medium calcium concentrations of 0.5 mmol/l and above, the lymphocyte calcium content was 1.0 mmol/l cells. In medium adjusted to 2 mmol/l calcium, the lymphocyte calcium content approximately doubled as the medium serum concentration was increased from 0 to 2%. At medium serum concentrations of 2% and above, lymphocyte calcium content was 2 mmol/l cells. The exchangeable cell calcium, measured with 45Ca in the same samples, did not increase as serum was added to the medium.


The effects of malvidin on oxidative stress parameters and inflammatory cytokines in LPS-induced human THP-1 cells.
Malvidin is an anthocyanin which is involved in inhibiting inflammatory-related mediators in inflammatory diseases; however, its mechanism of action in THP-1 cells is not yet known. THP-1 is a human monocytic cell line that is derived from patients with acute monocytic leukemia. The present study aimed to investigate the effect of malvidin on inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced THP-1 cells. THP-1 cells were stimulated with LPS (50 ng/ml) to induce inflammation in the presence or absence of malvidin. The anti/proinflammatory cytokines were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Total protein levels/phosphorylation of c-Jun N-terminal kinase (JNK), P65-NF-κB, and IKKα/IKKβ were evaluated by western blot analysis. Malondialdehyde (MDA) and nitric oxide (NO) metabolite levels, ferric reducing antioxidant power (FRAP), total thiol (T-SH) content, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were measured to evaluate the antioxidant activity of malvidin in THP-1 cells. Treatment of LPS-stimulated THP-1 cells with malvidin (100 and 200 μM) led to the significant inhibition of interleukin-6 (IL-6), tumor necrosis factor-α, and IL-1β messenger RNA (mRNA) expression and protein levels as well as a significant increase in the IL-10 mRNA expression and protein secretion. Moreover, 200 μM malvidin treatment reduced the phosphorylation of JNK, IKKα/IKKβ, and P65-NF-κB. These findings showed that malvidin not only decreased the MDA and NO metabolite levels but also increased the FRAP and T-SH content as well as SOD and GPx activities. The findings of the present study demonstrated the potential role of malvidin in blocking inflammation and oxidative stress induced by LPS in THP-1 cell line, suggesting that malvidin is likely to be a therapeutic agent for inflammatory diseases.


Detecting differences with magnetoencephalography of somatosensory processing after tactile and electrical stimuli.
Deviant stimuli within a standard, frequent stimulus train induce a cortical somatosensory mismatch response (SMMR). The SMMR reflects the brain's automatic mechanism for the detection of change in a somatosensory domain. It is usually elicited by electrical stimulation, which activates nerve fibers and receptors in superficial and deep skin layers, whereas tactile stimulation is closer to natural stimulation and activates uniform fiber types. We recorded SMMRs after electrical and tactile stimuli. 306-channel magnetoencephalography recordings were made with 16 healthy adults under two conditions: electrical (eSMMR) and tactile (tSMMR) stimulations. The SMMR protocol consisted of 1000 stimuli with 10% deviants to fingers. Sensor-level analysis revealed stronger activation after deviant stimulation in bilateral channel locations approximately corresponding to parietal cortical areas within both stimulation conditions. Between conditions, deviant tSMMR showed stronger activation in the ipsilateral channels. Based on sensor-level results, two components, M50 and SMMR (40-58 and 110-185 ms), were compared at the source-level. Deviant stimulation elicited stronger contralateral SI activation during M50 component in both conditions. SMMR was observed with both conditions, activating contralateral SII after deviant stimulation. However, only tSMMR showed long latency activation in bilateral SI cortices. This suggests that there is an integration of both body sides during the automatic stages of tactile processing in SI cortices. This study indicates that tactile stimulation (tSMMR) is a feasible method for investigating the brain's mechanism for detecting somatosensory changes; this may extend the clinical utility of tSMMR for assessing disorders involving altered somatosensory processing.


Clinical comparison of 6 aberrometers. Part 1: Technical specifications.
To provide a detailed assessment of the techniques, technical features, and practical use of 6 aberrometers made available to our institution from September 2002 to January 2004. Department of Ophthalmology, University Hospital Antwerp, Antwerp, Belgium. A number of technical and practical parameters are listed for the Visual Function Analyzer (Tracey), the OPD-scan (ARK 10000; Nidek), the Zywave (Bausch & Lomb), the WASCA (Carl Zeiss Meditec), the MultiSpot Hartmann-Shack device, and the Allegretto Wave Analyzer including working principles, data acquisition, aberrometer alignment, wavefront calculation, and data analysis. Operator and patient comfort as well as practical advantages and disadvantages are discussed. All devices met at least half the following parameters: alignment, correction for source wavelength, data averaging, measurement quality check, and inhibition of accommodation.


A fast and accurate method for registration of MR images of the head.
This paper proposes a new fully automated technique that can be used for the registration of medical images of the head. The method uses Chebyshev polynomials in order to approximate and then minimize a novel multiresolutional, signal intensity independent disparity function, which can generally be defined as the mean squared value of the mean weighted ratio of two images. This function is explicitly computed for n Chebyshev points in a geometric transformation parameter interval [-A, +A] transformation units and is approximated using the Chebyshev polynomials for all other points in the interval. For 3D T2-T1 weighted MR registration, 120 experiments with studies from ten patients were performed and showed that n = 4 Chebyshev points for A = 18 transformation units give mean rotational error 0.36 degrees and a mean translational error 0.36 mm. The different noise conditions did not affect the performance of the method. We conclude that the method is suitable for routine clinical applications and that it has significant potential for future development and improvement.


Biliary duct stones: percutaneous transhepatic removal.
Percutaneous transhepatic removal of common bile duct stones was performed 57 times in 53 patients with a success rate of 93%. All patients had contraindications to surgery or had undergone unsuccessful attempts at endoscopic retrograde cholangiopancreatography and papillotomy. A modified Dormia basket was inserted through a percutaneous transhepatic approach and the stones or fragments were advanced into the duodenum. Monooctanoin (26 patients) or methyl tertiary butyl ether (4 patients) was infused to reduce stone size or remove residual debris. The average time for complete stone removal was 8.5 days. Morbidity was 12% and mortality was 4%, results which compare favorably with those of surgery.


The rule of 1s for padding kinematic data prior to digital filtering: influence of sampling and filter cutoff frequencies.
The influence of signal sampling frequency and the low-pass digital filter cutoff frequency on the minimum number of padding points when applied to kinematic data are factors often absent in data processing descriptions. This investigation determined a relationship between the number of padding points and the ratio of filter cutoff to signal sampling frequencies (f(c)/f(s)). Two kinematic recordings were used which represented signals with high and low deterministic variation magnitudes at the signals' beginning. Signal sampling rates (40-128 Hz) were generated at intervals of 1 Hz. Filter cutoff frequency was iterated from 2 to 10 Hz at 0.5 Hz intervals. Data extrapolation was performed using three different techniques (first order polynomial, third order polynomial, and data reflection). A maximum of 2s of padding points were added to the beginning of each test signal which was then dual-pass filtered using a second order Butterworth filter. For each successive increase in the number of padding points, the filtered test signal was compared to a criterion signal and the root mean square difference (RMSD) over the first second was calculated. The number of padding points required to attain a constant RMSD was recorded as the minimum number of padding points needed for that ratio of filter cutoff to sampling frequency. As f(c)/f(s) increased, the number of padding points decreased non-linearly. More padding points were required for the signal with higher deterministic variation at the beginning than the signal with lower deterministic variation. Additional padding points (beyond the determined minimum) did not further reduce the RMSD. The largest temporal extrapolation determined by the algorithm to produce a stable RMSD was 1s. It is suggested that a minimum of 1s of extraneous data be used when using a low-pass recursive digital filter to remove noise from kinematic data.


Surgical measurement to sphenoid sinus for the Chinese in Asia based on CT using sagittal reconstruction images.
The objective this study was to measure the changes of sphenoid sinusin the Chinese in AsiausingCT sagittal thin-slice reconstruction images, and to clarify the three-dimensional anatomical features of sphenoid sinus with its surrounding structures, relevant to the performing of the endoscopic sphenoidotomy. The sagittal reconstruction images were obtained from 178 CT images of 89 cases of normal adult participants (54 males and 35 females) with sphenoid sinus. We took the high-resolution axial CT images, from all the subjects, of the thickness by 0.625 mm, and reconstructed 1-mm-thick gapless sagittal CT images to measure the distance of all the sellar and pre-sellar types on the three-dimensional reconstructable sagittal plane under the bone window (4,000 at its width, and 400 at its level) in the CT images. The length of mean vertical line from the center of sphenoid ostium to the roof of sphenoid sinus of Non Onodi cell type is 10.6 ± 1.5 mm, and of Onodi cell type is 3.3 ± 1.5 mm. The length of vertical line from the center of sphenoid ostium to the lowest level of the bottom of sphenoid sinus is 12 mm ± 3.7 mm. The length of mean horizontal line from the sphenoid ostium to the posterior wall of sphenoid sinus is 18 ± 1.5 mm or 28 ± 2.5 mm. The mean horizontal line from the lowest point of the sella to the anterior wall of sphenoid sinus is 17.5 ± 1.3 mm in length. The mean horizontal distance from anterior wall to posterior wall of sphenoid sinus of Non Onodi cell type lining skull base is 10.1 ± 1.0 mm, and of Onodi cell type, is 5.2 ± 4.3 mm. The longest horizontal distance from the anterior wall to the posterior wall of sphenoid sinus is 22.0 ± 7.7 mm. The present study provides atomical information about sphenoid sinus of the Chinese in Asia with some surgical distance measured between the sphenoid ostium and the surrounding structures, which is essential to avoid the complications during surgery.


Oxygen myelography for cervical spinal cord injuries.
Oxygen myelographies were performed on 15 patients with cervical spinal cord injuries, in seven of whom narrowing of the spinal cord was caused by a fracture-dislocation. In eight the fracture was of bursting type, and the neurological involement in these was more severe than in the former type. The main findings in seven early myelograms were swelling of the cord (3/7) and non-visualization of the spinal canal at the injury level (6/7). The main findings in eight late myelograms were narrowing of the cord (5/8) and anterior stretching of the cord over the obstructing bony ridge.


Shifts in antimicrobial consumption and infection rates before and during a piperacillin/tazobactam shortage.
Anti-infective shortages represent a growing threat to optimum management of infected patients and alter the institutional selective pressure against hospital-acquired infections (HAIs). The objective of this analysis was to assess the impact of a shortage of piperacillin/tazobactam (TZP) on overall antibacterial use and HAI rates at an academic institution. Antimicrobial use and infection data were extracted from TheraDoc Clinical Surveillance Software (Premier, Inc.) for adult patients and were stratified as pre-shortage (October-December 2014) and post-shortage (February-April 2015). Paediatric and emergency department use were excluded. Antimicrobial use was reported as percent change and defined daily doses (DDD)/1000 patient-days (PD). Pre- and post-shortage vancomycin-resistant enterococci (VRE) and Clostridium difficile-associated diarrhoea (CDAD) rates were normalised to 1000 PD/month. Total use of target antimicrobials remained constant before and after TZP shortage (990.29 vs. 957.77). Total TZP use fell 95.2% (81.1 vs. 3.9). Total meropenem use rose 96.0% (42.3 vs. 82.9) after the shortage, driven by a 125.4% increase in use for non-ICU patients. Cefepime and ceftazidime use rose 97.9% (28.2 vs. 55.8) and 94.2% (1.6 vs 3.0), respectively. Cefepime use in non-ICU patients rose 223.2%. Fluoroquinolone consumption did not differ between periods. CDAD rates decreased (-21.8%), whilst VRE rates doubled during the shortage (0.6 vs. 1.3 infections/1000 PD/month). Whilst overall antimicrobial use appeared steady, the TZP shortage resulted in increased use of multiple other antimicrobials. The doubling of VRE rates is concerning and illustrates the need for increased antimicrobial stewardship vigilance and education in response to shifting prescribing patterns during shortages.


Seat belts: a study of their use by the victims of road traffic accidents.
This paper reports a study of 266 patients who were admitted to an Accident Service after being involved in road traffic accidents during the four-month period from February to May in 1976. There were 216 front-seat occupants, of whom 21 per cent were wearing seat belts: 156 patients were treated as outpatients and 105 patients were admitted to the wards. Five patients were dead on arrival, none of whom had been wearing a seat belt. There was a significant reduction in the likelihood of being admitted as an impatient (P less than 0.05) if a seat belt was used. There was an 11 per cent increase in the use of seat belts compared with a similar study carried out in 1971 and random roadside surveys also showed a 10 per cent increase. The implications of these findings are discussed.


Effects of glucose starvation and puromycin treatment on lipid-linked oligosaccharide precursors and biosynthetic enzymes in Chinese hamster ovary cells in vivo and in vitro.
Previous studies from several laboratories have demonstrated that glucose-starved Chinese hamster ovary (CHO) cells and other cells in culture switch from synthesis of the normal Glc3Man9GlcNAc2-P-P-Dol to Man5-GlcNAc2-P-P-Dol. In this study we have investigated this phenomenon in CHO cells in vitro and in vivo in order to determine the possible site of this block. Our results demonstrate that enzymatic activities responsible for Man9GlcNA2 synthesis in vitro are normal in glucose-starved cells. In vivo, however, the pool of GDP-[3H]Man is severely depleted, while [3H]mannose incorporation into lipid-linked and protein-bound Man5GlcNAc2 is increased. This result suggests that the available GDP-Man in starved cells is utilized to synthesize Man5GlcNAc2 preferentially, resulting in a reduction of Dol-P-Man and Man6-Man9 GlcNAc2 synthesis in vivo in glucose-starved cells. Conditions which prevent the depletion of GDP-[3H]Man in glucose-starved cells, such as puromycin or cycloheximide treatment, result in normal synthesis of Man9GlcNAc2 by glucose-starved cells. An unexpected finding in the course of this study is that puromycin or cycloheximide treatment of cells, which is known to inhibit lipid-linked oligosaccharide synthesis in glucose-fed cells, has no such inhibitory effect on glucose-starved cells.


Keloids and hypertrophic scars in the foot.
The occurrence of keloids in the foot is rare but should always be a surgical consideration for those individuals who may be predisposed to this pathology. Failure to recognize the potential for keloids or hypertrophic scar development may result in a severe deformity that is functionally, cosmetically, and emotionally undesirable.


In vitro 3H-serotonin (5-HT) synthesis and release in BALBc and C57BL mice. II. Cell body areas.
"In vitro" 3H-5-HT and 3H-5-HIAA, newly synthesized from 3H-TRP, are measured in the brainstem, the anterior raphe nuclei and the locus coeruleus of C57BL and BALBc mice. As found for the caudate nucleus and the hippocampus, higher synthesis and release are determined in C57BL than in BALBc, for the locus coeruleus and more globally, for the brainstem. But these differences disappear when the study is carried on the raphe dorsalis and the raphe centralis nuclei. Therefore the serotonergic activity could be independently regulated at the level of cell bodies and at those of terminals. However, the 5-HT metabolism of NRD of BALBc mice could be submitted to a specific autoinhibition which could explain a lower 5-HT synthesis and release at the corresponding terminal level, compared to C57BL.


Plasma dexamethasone kinetics during the DST after oral and intravenous administration of the test drug.
We compared early biophase kinetics of dexamethasone in 33 patients with a major depression who received a DST either by an oral (n = 20) or an intravenous (n = 13) route. After an oral DST, the dexamethasone kinetics between 14 suppressors and 6 nonsuppressors were indistinguishable during the early distribution phase. However, elimination of dexamethasone from the circulation was significantly enhanced in DST nonsuppressors, resulting in an association of decreased plasma dexamethasone with elevated post-DST cortisol levels. Following intravenous DST administration, we identified 5 nonsuppressors and 8 suppressors whose plasma dexamethasone kinetics were indistinguishable, and during the elimination phase, were in the same order of magnitude as those of nonsuppressors after an oral DST. We suggest that the actual plasma concentration at the conventional post-DST sampling times does not reflect the biopotency of the test drug to suppress the pituitary adrenocortical activity. Plasma dexamethasone concentrations after an oral DST that were associated with nonsuppressed cortisol seem to be coherent phenomena of the underlying endocrine disturbance, the precise nature of which deserves further study.


Regional Disruptions in Endothelial Nitric Oxide Pathway Associated With Bicuspid Aortic Valve.
Endothelial nitric oxide (NO) synthase (eNOS) has been implicated in the development of bicuspid aortic valve (BAV) and with differential expression in the ascending aorta of BAV patients. However, little is known about functional disruptions in the eNOS pathway and the effect on BAV-associated aortic dilatation. We tested the hypothesis that eNOS function is regionally diminished in ascending thoracic aortic aneurysms associated with BAV. Thoracic aortic aneurysms specimens were collected from patients with BAV (n = 21) or tricuspid aortic valve (n = 12). Tissue samples were harvested from three circumferential regions corresponding to locations above the right, left, and noncoronary sinuses. Adventitial-stripped specimens containing media and intima only were analyzed for NO synthase 3 gene expression and total eNOS protein. Indicators of eNOS activity (pSer1177-eNOS) and NO bioavailability (phosphorylation of vasodilator-stimulated phosphoprotein at Ser239) were also measured. NO synthase 3 and eNOS protein were elevated in the right aortic region of BAV specimens compared with tricuspid aortic valve specimens. Activation of eNOS, as indicated by pSer1177-eNOS, was higher in BAV specimens across all regions. Despite increases in eNOS and pSer1177-eNOS, BAV specimens displayed no change in pSer239-vasodilator-stimulated phosphoprotein compared with tricuspid aortic valve specimens. BAV is associated with regional disruptions in the eNOS pathway, most markedly in the right aortic region. The discrepancy between increased eNOS activity and the absence of increased NO bioavailability in this region provides insight into physiologic mechanisms potentially underlying the asymmetric dilatation pattern observed in BAV.


Carbon dioxide fluxes in a spatially and temporally heterogeneous temperate grassland.
Landscape position, grazing, and seasonal variation in precipitation and temperature create spatial and temporal variability in soil processes, and plant biomass and composition in grasslands. However, it is unclear how this variation in plant and soil properties affects carbon dioxide (CO2) fluxes. The aim of this study is to explore the effect of grazing, topographic position, and seasonal variation in soil moisture and temperature on plant assimilation, shoot and soil respiration, and net ecosystem CO2 exchange (NEE). Carbon dioxide fluxes, vegetation, and environmental variables were measured once a month inside and outside long-term ungulate exclosures in hilltop (dry) to slope bottom (mesic) grassland throughout the 2004 growing season in Yellowstone National Park. There was no difference in vegetation properties and CO2 fluxes between the grazed and the ungrazed sites. The spatial and temporal variability in CO2 fluxes were related to differences in aboveground biomass and total shoot nitrogen content, which were both related to variability in soil moisture. All sites were CO2 sinks (NEE>0) for all our measurements taken throughout the growing season; but CO2 fluxes were four- to fivefold higher at sites supporting the most aboveground biomass located at slope bottoms, compared to the sites with low biomass located at hilltops or slopes. The dry sites assimilated more CO2 per gram aboveground biomass and stored proportionally more of the gross-assimilated CO2 in the soil, compared to wet sites. These results indicate large spatio-temporal variability of CO2 fluxes and suggest factors that control the variability in Yellowstone National Park.


[Sialolithiasis: Current Diagnostics and Therapy].
Sialolithiasis is one of the most common salivary gland diseases. The main symptom is acute swelling of a major salivary gland after food intake, whereby the submandibular gland is significantly more frequently affected compared to the parotid gland. In the course of the disease, recurrent sialadenitis occurs in many cases. In addition to submandibulectomy, there is currently not only the possibility of improved diagnostics but also of gland-preserving therapy, for example by means of miniature endoscopy (sialendoscopy).


Exercise reduces cellular stress related to skeletal muscle insulin resistance.
This study sought to evaluate the effects of a single session of exercise on the expression of Hsp70, of c-jun N-terminal kinase (JNK), and insulin receptor substrate 1 serine 612 (IRS(ser612)) phosphorylation in the skeletal muscle of obese and obese insulin-resistant patients. Twenty-seven volunteers were divided into three experimental groups (eutrophic insulin-sensitive, obese insulin-sensitive, and obese insulin-resistant) according to their body mass index and the presence of insulin resistance. The volunteers performed 60 min of aerobic exercise on a cycle ergometer at 60 % of peak oxygen consumption. M. vastus lateralis samples were obtained before and after exercise. The protein expressions were evaluated by Western blot. Our findings show that compared with paired eutrophic controls, obese subjects have higher basal levels of p-JNK (100 ± 23 % vs. 227 ± 67 %, p = 0.03) and p-IRS-1(ser612) (100 ± 23 % vs. 340 ± 67 %, p < 0.001) and reduced HSP70 (100 ± 16 % vs. 63 ± 12 %, p < 0.001). The presence of insulin resistance results in a further increase in p-JNK (460 ± 107 %, p < 0.001) and a decrease in Hsp70 (46 ± 5 %, p = 0.006), but p-IRS-1(ser612) levels did not differ from obese subjects (312 ± 73 %, p > 0.05). Exercise reduced p-JNK in obese insulin-resistant subjects (328 ± 33 %, p = 0.001), but not in controls or obese subjects. Furthermore, exercise reduced p-IRS-1(ser612) for both obese (122 ± 44 %) and obese insulin-resistant (185 ± 36 %) subjects. A main effect of exercise was observed in HSP70 (p = 0.007). We demonstrated that a single session of exercise promotes changes that characterize a reduction in cellular stress that may contribute to exercise-induced increase in insulin sensitivity.


Stress-hyperglycemia, insulin and immunomodulation in sepsis.
Stress-hyperglycemia and insulin resistance are exceedingly common in critically ill patients, particularly those with sepsis. Multiple pathogenetic mechanisms are responsible for this metabolic syndrome; however, increased release of pro-inflammatory mediators and counter-regulatory hormones may play a pivotal role. Recent data suggests that hyperglycemia may potentiate the pro-inflammatory response while insulin has the opposite effect. Furthermore, emerging evidence suggests that tight glycemic control will improve the outcome of critically ill patients. This paper reviews the pathophysiology of stress hyperglycemia in the critically ill septic patient and outlines a treatment strategy for the management of this disorder.


Extension and application of multivariate curve resolution-alternating least squares to four-way quadrilinear data-obtained in the investigation of pollution patterns on Yamuna River, India--A case study.
This study focuses on the development and extension of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to the analysis of four-way datasets. The proposed extension of the MCR-ALS method with non-negativity and the newly developed quadrilinear constraints can be exploited to summarize and manage huge multidimensional datasets and resolve their four way component profiles. In this study, its application is demonstrated by analyzing a four-way data set obtained in a long term environmental monitoring study (15 sampling sites×9 variables×12 months×7 years) belonging to the Yamuna River, one of the most polluted rivers of India and the largest tributary of the Ganges river. MCR-ALS resolved pollution profiles described appropriately the major observed changes on pH, organic pollution, bacteriological pollution and temperature, along with their spatial and temporal distribution patterns for the studied stretch of Yamuna River. Results obtained by MCR-ALS have also been compared with those obtained by another multi-way method, PARAFAC. The methodology used in this study is completely general and it can be applied to other multi-way datasets.


Influence of several anesthetic agents on the effect of delta9-tetrahydrocannabinol on the heart rate and blood pressure of the mongrel dog.
delta9-Tetrahydrocannabinol (delta9-THC) 1 mg/kg, i.v. produced a slight but significant reduction in the heart rate of conscious mongrel dogs, and these effects were greatly potentiated by pentobarbital and/or urethane anesthesia. However, significant increase in the heart rate was noted following delta9-THC administration in the dogs anesthetized with a combination of morphine plus chloralose; further, neither morphine nor chloralose alone could reverse the bradycardic effects of delt9-THC. Tachycardia induced by delta9-THC in these dogs could be reversed by bilateral vagotomy or by pretreatment of the animals with methylatropine, or propranolol and/or practolol. The data indicated a complex interaction between delta9-THC and morphine-chloralose combination and the tachycardia induced by delta9-THC under this anesthesia may be due to release of epinephrine by a reflexogenic mechanism involving afferent vagi. Further, while the bradycardic effects of delta9-THC were essentially identical under pentobarbital or urethane anesthesia, the hypotensive effects were similar in urethane or chloralose anesthetized dogs. The study emphasizes that anesthetic interaction should be taken into consideration while investigating mechanisms of actions of pharmacological agents.


Radiographic osteoarthritis and serum cholesterol.
To find out the relationship between radiographic osteoarthritis (OA) of the knee, generalized OA and serum cholesterol. Over a period of 7 months from September 1998 through to March 1999, 246 patients attending 14 primary care clinics in Northern Riyadh, Kingdom of Saudi Arabia, for different non-musculoskeletal complaints were recruited in the study. Their knees, hands and wrists were radiographed. Their ages, sex, weight, height, body mass index (BMI), fasting serum cholesterol, triglycerides and uric acid were recorded. There were 113 females and 133 males with average ages 46 14.2 and 51.54 16.0 years. One hundred and twenty-two (49.6%) cases of knee OA and 58 (23.6%) cases of generalized OA were found and analyzed for the association with serum cholesterol levels. Crude odds ratio (OR) for the relationship between knee OA and the third tertile of serum cholesterol was 2.33 (95% CI, 1.19-4.58) which on adjusting for age, sex, BMI, serum uric acid and triglycerides were 2.68 (95% CI, 2.00-3.64). For generalized OA, the crude odds ratio (OR) in relation to the third tertile of serum cholesterol was 1.65 (95% CI, 0.78-3.53), adjusted OR was 2.18 (95% CI, 1.55-3.15). The results showed an association between high serum cholesterol level and both knee and generalized OA.


Lateral oropharyngeal wall and supraglottic airway collapse associated with failure in sleep apnea surgery.
To identify patterns of airway collapse during preoperative drug-induced sleep endoscopy (DISE) as predictors of surgical failure following multilevel airway surgery for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Retrospective clinical chart review. Medical records of patients who underwent site-specific surgical modification of the upper airway for treatment of OSHAS were reviewed. Patients were included in this study if they had a preoperative airway evaluation with DISE as well as preoperative and postoperative polysomnography. Airway obstruction on DISE was described according to airway level, severity, and axis of collapse. Severe airway obstruction was defined as >75% collapse on endoscopy. Surgical success was described as a postoperative apnea-hypopnea index (AHI) of <20 and a >50% decrease in preoperative AHI. A total of 34 patients were included in this study. The overall surgical success rate was 56%. Surgical success (n = 19) and surgical failure (n = 15) patients were similar with regard to age, gender, body mass index, preoperative AHI, Friedman stage, adenotonsillar grades, and surgical management. DISE findings in the surgical failure group demonstrated greater incidence of severe lateral oropharyngeal wall collapse (73.3% vs. 36.8%, P = .037) and severe supraglottic collapse (93.3% vs. 63.2%, P = .046) as compared to the surgical success group. The presence of severe lateral pharyngeal wall and/or supraglottic collapse on preoperative DISE is associated with OSAHS surgical failure. The identification of this failure-prone collapse pattern may be useful in preoperative patient counseling as well as in directing an individualized and customized approach to the treatment of OSHAS.


Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease.
Characteristic features of Parkinson's disease (PD) are asymmetric parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on transcranial ultrasound. However, each of these features has limited diagnostic value as they may be present, albeit less frequently, in other parkinsonian disorders. Here, the diagnostic sensitivity and specificity of combined assessment of these three features are evaluated. 632 patients with parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes, essential tremor and major depressive disorder with motor slowing) were assessed on the Unified Parkinson's disease Rating Scale for motor asymmetry (right-left score difference ≥2), the 12 item Sniffin' Sticks test (SS-12) and transcranial ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects (193 (35) women; age 65.4±9.6 (62.3±10.3) years) of whom 385 (68) had PD and 132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to missing transcranial insonability. Of the validation cohort, all patients had a disease duration ≤2 years and observers were blind to diagnoses. The optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia) and SN echogenic size ≥0.24 cm(2) (SN hyperechogenicity). Sensitivity, specificity and positive predictive values for the diagnosis of PD were as follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia 75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present 96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation cohort: two features present 91%, 77% and 85%; three features present 49%, 98% and 97%. The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.


Defining and Studying Errors in Surgical Care: A Systematic Review.
Our objective was to determine the extent surgical disciplines categorize, define, and study errors, then use this information to provide recommendations for both current practice and future study. The report "To Err is Human" brought the ubiquity of medical errors to public attention. Variability in subsequent literature suggests the true prevalence of error remains unknown. In January 2020, PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Only studies with Oxford Level of Evidence Level 3 or higher were included. Of 3064 studies, 92 met inclusion criteria: 6 randomized controlled trials, 4 systematic reviews, 24 cohort, 10 before-after, 35 outcome/audit, 5 cross sectional and 8 case-control studies. Over 15,933,430 patients and 162,113 errors were represented. There were 6 broad error categories, 13 different definitions of error, and 14 study methods. Reported prevalence of error varied widely due to a lack of standardized categorization, definitions, and study methods. Future research should focus on immediately recognizing errors to minimize harm.


The sweeter side of ACE2: physiological evidence for a role in diabetes.
Diabetes mellitus is a growing problem in all parts of the world. Both clinical trials and animal models of type I and type II diabetes have shown that hyperactivity of angiotensin-II (Ang-II) signaling pathways contribute to the development of diabetes and diabetic complications. Of clinical relevance, blockade of the renin-angiotensin system prevents new-onset diabetes and reduces the risk of diabetic complications. Angiotensin-converting enzyme (ACE) 2 is a recently discovered mono-carboxypeptidase and the first homolog of ACE. It is thought to inhibit Ang-II signaling cascades mostly by cleaving Ang-II to generate Ang-(1-7), which effects oppose Ang-II and are mediated by the Mas receptor. The enzyme is present in the kidney, liver, adipose tissue and pancreas. Its expression is elevated in the endocrine pancreas in diabetes and in the early phase during diabetic nephropathy. ACE2 is hypothesized to act in a compensatory manner in both diabetes and diabetic nephropathy. Recently, we have shown the presence of the Mas receptor in the mouse pancreas and observed a reduction in Mas receptor immuno-reactivity as well as higher fasting blood glucose levels in ACE2 knockout mice, indicating that these mice may be a new model to study the role of ACE2 in diabetes. In this review we will examine the role of the renin-angiotensin system in the physiopathology and treatment of diabetes and highlight the potential benefits of the ACE2/Ang-(1-7)/Mas receptor axis, focusing on recent data about ACE2.


An experimental investigation of life history and plasticity in two cytotypes of Polygonum aviculare L. subsp. aviculare that coexist in an abandoned arable field.
Polygonum aviculare subsp. aviculare is an annual selfing weed common in abandoned arable fields where it occurs as a widespread hexaploid cytotype (6x=60) and a rarer tetraploid cytotype (4x=40). The basis of phenological differentiation between the two cytotypes observed in a natural population where they coexist was examined in a greenhouse experiment comprising six soil conditions consisting of factorial combinations of two levels of fertility and three pot sizes. The environmental and genetic component of variation in 11 life history and morphological traits was quantified. Even though all traits except life span were plastic the two cytotypes appear to have evolved contrasting life history strategies and it is inferred that this can account for the temporal niche differentiation observed in the abandoned field during the first year of dereliction. Tetraploids are short-lived plants allocating a high proportion of their biomass to reproduction and completing their life cycle before July when the plant cover is sparse. Hexaploids are larger, later flowering, longer lived, plants with a lower reproductive effort and a higher final seed yield; it is inferred that these traits enable the hexaploids to compete successfully with the dense herbaceous layer of summer annuals that develops in the course of the first year of secondary succession. Differentiation in phenotypic plasticity between the two cytotypes was interpreted as indicative of higher opportunism and lower tolerance of poor soils and restricted rooting space in the hexaploid compared to the tetraploid cytotype.


Hot-water epilepsy: a variant of reflex epilepsy in southern India.
"Hot water epilepsy" (HWE), precipitated by a bath or shower in hot water, has been described infrequently in the literature. We report 279 cases of HWE that were seen between 1980 to 1983 in Bangalore, South India. We found HWE to be more common in children, with cases more frequent among male than female patients (2.6:1). Complex partial seizures constituted the main clinical presentation (67.0%); HWE accounted for 4.4% of all complex partial seizures and generalize tonic-clonic seizures seen at our center during the 1980-1983 period. Although prognosis seems favorable 25.4% of our patients developed nonreflex epilepsy within 1-3 years. They were managed with antiepileptic drugs and the use of lukewarm water for bathing.


Temperature-sensitive translation of MS2 bacteriophage RNA.
A comparison was made of bacteriophage MS2 RNA translation in infected Escherichia coli cells and in a defined cell-free system. A number of temperature-sensitive mutants were used as hosts for viral RNA translation at permissive and restrictive temperatures. The amount of viral coat protein synthesis was determined after gel electrophoresis of proteins from the cell lysates. These results were compared to those obtained with cell-free translation assays conducted with ribosomes isolated from the same mutants. Compared with control cells, a reduced activity in vivo and in vitro was found for each mutant examined at elevated temperatures. A good correlation between the two types of translational assays was observed. These findings are discussed in terms of the translational defects known to be a characteristic of some of these mutant strains.


Time out: Prediction of self-exclusion from daily fantasy sports.
Responsible gambling (RG) tools that include play management software, self-limit features, and self-exclusion are relatively common offerings on major online gambling platforms. However, how online gaming and daily fantasy sports (DFS) players use such tools is less clear. The goals of this article were to understand how players use self-exclusion at a major DFS platform and to identify DFS activity-related predictors of self-exclusion. During November 2015, DraftKings, a major DFS provider, rolled out a self-exclusion feature that allows players to self-exclude from the platform for a specified amount of time, up to 5 years. We used player records from DraftKings, examining play patterns and self-exclusion across 3 + years of data. We found that less than 0.5% of subscribers in our sample self-excluded during the study period and almost one third of those who self-excluded did so more than once. In general, self-excluders engaged with a greater variety of contests and sports and entered contests with higher entry fees than those who did not self-exclude. Repeat self-excluders selected shorter initial self-exclusion terms and also engaged with a greater variety of game types and sports than one-time self-excluders. However, self-excluders did not engage in riskier contests or experience higher percent losses. Our findings have implications for our understanding of RG feature use among DFS subscribers and markers of risk for experiencing problems with DFS and gambling more generally. (PsycInfo Database Record (c) 2022 APA, all rights reserved).