Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis.
Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < or = 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < or = 0.01) and the 400-mg groups (P < or = 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin.(ABSTRACT TRUNCATED AT 250 WORDS)


Monocyte chemoattractant protein-1 is a pathogenic component in a model for a hereditary peripheral neuropathy.
Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in models for inherited demyelinating neuropathies. It is presently unknown which factors link the Schwann cell-based myelin mutation to the activation of endoneurial macrophages. Here we identified the chemokine monocyte chemoattractant protein-1 (MCP-1) as a first and crucial factor upregulated in Schwann cells of mice heterozygously deficient for the myelin protein zero. The chemokine could be identified as an important mediator of macrophage immigration into peripheral nerves. Furthermore, a 50% reduction of chemokine expression by crossbreeding with MCP-1-deficient mice reduced the increase in macrophage numbers in the mutant nerves and lead to a robust amelioration of pathology. Surprisingly, the complete absence of MCP-1 aggravated the disease. Our findings show that reducing but not eliminating chemokine expression can rescue genetically caused demyelination that may be an interesting target in treating demyelinating diseases of the peripheral nervous system.


Intravitreal Injections of Voriconazole for Candida Endophthalmitis: A Case Series.
Purpose: Candida endophthalmitis represents a therapeutic challenge, considering the inability of many antifungals to achieve adequate concentrations in the vitreous. Intravitreal injection (IVI) of antifungals (amphotericin b deoxycholate or voriconazole) is therefore recommended. Whereas amphotericin b IVI is well documented, clinical data on voriconazole IVI are limited.Methods: This was a retrospective review IRB approved of patients receiving voriconazole IVI for Candida endophthalmitis. Complete ophthalmological examination was completed at baseline and during follow-up.Results: Five patients were treated with a mean four injections [range: 2-9] of voriconazole (100 µg/0.1 mL saline). Improvement of visual acuity and disappearance of signs of infection were obtained in all patients. Safety concern including photoreceptor toxicity was not attributed to voriconazole IVI.Conclusions: Voriconazole IVI demonstrated to be safe and led to a favorable clinical outcome. Thus, voriconazole IVI must be performed if Candida endophthalmitis is suspected to increase the chance of clinical success.


Effect of polymerization temperature on the properties of autopolymerizing resin.
The polymerization conditions of an autopolymerizing resin affect its physical properties, and at chairside, 3 different methods are commonly used: cooling in cold water, warming in warm water, and heating in hot water. However, the effects of polymerization temperature on the physicomechanical properties of autopolymerizing resin are unclear. The purpose of this in vitro study was to determine the effect of polymerization temperature on the physicomechanical properties of autopolymerizing resin, including shrinkage, water absorption, surface roughness, amount of residual monomer, and flexural strength. The experiment was designed to simulate a direct technique commonly used for the fabrication of interim crowns. Autopolymerizing resin specimens were made according to the powder-to-liquid ratio recommended by the manufacturer and soaked in water at 13°C, 37°C, or 60°C for 2 minutes to mold the resin until polymerization was completed 4 minutes after mixing. Shrinkage, water absorption rate, surface roughness, residual monomer, and flexural strength were measured immediately after polymerization and after 1, 3, and 7 days in distilled water at 37°C. Differences among these properties among the 3 different temperatures groups were statistically analyzed by using 1-way ANOVA and the Tukey honest significant difference test (α=.05). Shrinkage tests showed that the 13°C group had significantly lower shrinkage (P=.004 for 37°C and P<.001 for 60°C) than the other groups immediately after specimen preparation. The 13°C group had significantly higher surface roughness after 0 (P<.001 for 37°C and P<.001 for 60°C), 1 (P=.025 for 37°C and P=.012 for 60°C), 3 (P<.001 for 37°C and P<.001 for 60°C), and 7 days (P<.001 for 37°C and P<.001 for 60°C) than those in the other groups and significantly higher water absorption rates (P=.033 for 37°C and P<.001 for 60°C) than the other groups during the 7 days after fabrication. However, the 13°C group showed significantly higher weight percentage of residual monomers than the 60°C group at 0 (P<.001) and 1 day (P<.001). Finally, 3-point bend tests showed that the 13°C group had significantly lower flexural strength at 0 (P<.001), 1 (P<.001), 3 (P<.001), and 7 days (P<.001) than the other groups. The temperature environment during dental chairside polymerization of the autopolymerizing resin affected the physicomechanical properties of shrinkage, water absorption rate, surface roughness, residual monomer, and flexural strength.


Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity.
Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Mason's vertical banded gastroplasty. Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second. On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology. NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients.


Quantitation of green fluorescent protein using a gel-based imaging method.
Green fluorescent protein (GFP) is a versatile reporter protein and has been widely used in biological research. However, its quantitation requires expensive equipment such as a spectrofluorometer. In the current study, a gel documentation imaging system using a native polyacrylamide gel for the quantitation of GFP was developed. The assay was evaluated for its precision, linearity, reproducibility, and sensitivity in the presence of Escherichia coli cells and was compared with the spectrofluorometric method. Using this newly established, gel-based imaging technique; the amount of GFP can be quantified accurately.


Erythrocyte lipid composition and sodium transport in human liver disease.
In patients with liver disease there are usually increases in erythrocyte cholesterol and phosphatidylcholine concentrations. This increase in membrane lipid changes the shape of the erythrocyte and "spur" or "target" cells may be present. Sodium fluxes were measured in erythrocytes from 17 patients with a variety of liver diseases and from 17 normal subjects and the values related to the lipid content of the membrane. Ouabain-insensitive and ouabain-sensitive effluxes were lower in patients than in normal subjects and the reduction in ouabain-insensitive efflux was more marked. Sodium influx was also significantly lower in erythrocytes from patients than controls. Ouabain-sensitive and ouabain-insensitive effluxes and sodium influx did not correlate with the cholesterol content of erythrocytes from patients. Significant negative correlations were noted between ouabain-insensitive sodium efflux (r=--0.63, P less than 0.01), sodium influx (r=--0.61, P less than 0.01) and intracellular sodium concentration (r=--0.66, P less than 0.01) and the cholesterol : phospholipid molar ratio of the cell but there was no significant correlation between this ratio and the ouabain-sensitive sodium efflux (r=0.41, P less than 0.05). These results support the hypothesis that an altered lipid composition may affect the permeability of the erythrocyte membrane in patients with liver disease.


Diffusion tensor imaging using partial Fourier STEAM MRI with projection onto convex subsets reconstruction.
Diffusion-weighted single-shot STEAM MRI allows for diffusion mapping of the human brain without sensitivity to resonance offset effects. In order to compensate for its inherently lower SNR and speed than echo-planar imaging, this work describes the use of partial Fourier encoding in combination with image reconstruction by the projection onto convex subsets algorithm. The method overcomes phase distortions in diffusion-weighted partial Fourier acquisitions that disturb the conjugate complex symmetry of k-space and preclude the use of respective reconstruction techniques. In comparison with full Fourier encoding and a static flip angle for the STEAM readout pulses, experimental results at 2.9 T demonstrate a gain in relative SNR per unit time by 20% for 5/8 phase encoding with optimized variable flip angles. Simultaneously, the imaging time is reduced from about 670 ms (80 echoes) to 440 ms (50 echoes). Current implementations at 2 x 2 mm2 in-plane resolution comprise a protocol for clinical anisotropy studies (12 diffusion-encoding gradient directions at 1000 s mm(-2)) covering 18 sections of 4-mm thickness within a measurement time of 8.5 min (5 averages) and a version optimized for fiber tracking using 24 gradient directions and 38 sections of 2-mm thickness yielding a measurement time of 29.5 min (4 averages).


EIGER2 hybrid-photon-counting X-ray detectors for advanced synchrotron diffraction experiments.
The ability to utilize a hybrid-photon-counting detector to its full potential can significantly influence data quality, data collection speed, as well as development of elaborate data acquisition schemes. This paper facilitates the optimal use of EIGER2 detectors by providing theory and practical advice on (i) the relation between detector design, technical specifications and operating modes, (ii) the use of corrections and calibrations, and (iii) new acquisition features: a double-gating mode, 8-bit readout mode for increasing temporal resolution, and lines region-of-interest readout mode for frame rates up to 98 kHz. Examples of the implementation and application of EIGER2 at several synchrotron sources (ESRF, PETRA III/DESY, ELETTRA, AS/ANSTO) are presented: high accuracy of high-throughput data in serial crystallography using hard X-rays; suppressing higher harmonics of undulator radiation, improving peak shapes, increasing data collection speed in powder X-ray diffraction; faster ptychography scans; and cleaner and faster pump-and-probe experiments.


Congenital analbuminaemia: molecular defects and biochemical and clinical aspects.
DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA). To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. Study of the defects in the ALB resulting in CAA allows the identification of "hot spot" regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.


GDPmannose dehydrogenase and biosynthesis of alginate-like polysaccharide in a mucoid strain of Pseudomonas aeruginosa.
GDPmannose dehydrogenase (EC 126.96.36.199) in a mucoid strain of Pseudomonas aeruginosa isolated from a patient with cystic fibrosis was identified by demonstrating the NAD-linked formation of GDPmannuronate from GDPmannose mediated by a cell extract of the organism. Nonmucoid mutant strains did not contain GDPmannose dehydrogenase, which suggests that the enzyme is involved in the biosynthesis of alginate-like polysaccharide by P. aeruginosa.


Feasibility and accuracy of using different methods to detect pregnancy by conceptus-stimulated genes in dairy cattle.
Development of new methods for early diagnosis of pregnancy can be important to increase the reproductive efficiency and profitability of dairy herds. The bovine conceptus secretes IFN-τ that stimulates the transcription of several genes in circulating immune cells and extrauterine tissues. The aims of this study were to evaluate the mRNA abundance for pregnancy predictability of a classic gene stimulated by IFN-τ (ISG15) and a novel potential pregnancy marker (LGALS3BP) in peripheral blood mononuclear cells (PBMC), total blood leukocytes (TBL) or milk leukocytes (TML), and cervical cells (CC) on d 20 after timed artificial insemination (TAI) in dairy cattle. Eighteen Holstein females (12 cows and 6 heifers) were submitted to an estrous synchronization protocol for TAI (d 0). On d 20 post-TAI, blood samples were collected from coccygeal vessels for isolation of PBMC and in Tempus Blood RNA tubes (Applied Biosystems) for TBL. Samples of CC were collected using a cytological brush, and the TML were isolated from milk samples collected before routine milking. Pregnancy diagnosis was performed on d 30 post-TAI using transrectal ultrasonography, and females were classified as pregnant (n = 8) or nonpregnant (n = 10). Total RNA was extracted and mRNA abundance of target genes (ISG15 and LGALS3BP) was quantified by reverse-transcription quantitative PCR and normalized in relation to reference genes. Data were analyzed by ANOVA using the MIXED procedure of SAS (SAS Institute Inc.). The mRNA abundance of ISG15 was greater in pregnant than in nonpregnant animals for PBMC, TBL, and CC. No difference was detected for TML based on pregnancy status. For LGALS3BP mRNA abundance, no difference was detected between pregnant and nonpregnant animals for PBMC, TBL, and TML, but a tendency for greater abundance in pregnant animals was observed for CC. The fold change for ISG15 in each pregnant cow related to the mean of nonpregnant animals was 2.73 ± 0.31, 3.40 ± 2.17, 1.64 ± 0.29, and 0.005 ± 0.002 for PBMC, CC, TBL, and TML, respectively. The fold change for LGALS3BP in each pregnant cow related to the mean of nonpregnant animals was 0.97 ± 0.38, 1.77 ± 0.39, 0.20 ± 0.08, and 0.70 ± 0.11 for PBMC, CC, TBL, and TML, respectively. The receiver operating characteristic curve analysis indicated that ISG15 abundance predicted pregnancy in PBMC (area under curve, AUC = 0.92) and CC (AUC = 0.77) but not in TBL (AUC = 0.72) or TML (AUC = 0.52). In conclusion, mRNA abundance for ISG15 in PBMC was the best predictor for pregnancy at d 20 post-TAI, whereas TBL and TML were not good predictors of pregnancy on d 20 post-TAI. The mRNA abundance of LGALS3BP was not associated with pregnancy status in any type of cell evaluated.


The Emergency Department presenting complaint as predictor of in-hospital fatality.
The relationship between major discharge diagnoses and prediction of in-hospital death has been intensively studied. The relation between the presenting complaint at the Emergency Department (ED) and in-hospital fatality, however, is less well known. To investigate if presenting complaints add information regarding in-hospital fatality risk for nonsurgical ED patients. Investigating the relationship of in-hospital fatality rate and presenting complaint by comparing the presenting complaints, discharge diagnoses and in-hospital fatality for all nonsurgical patients visiting the ED during 1 year. Of 12,995 nonsurgical admissions, 40% were treated as in-hospital patients. Among these, 328 in-hospital deaths occurred. Age was the most powerful predictor of death in hospitalized patients (P<0.0001). After adjustment for age, the female sex was found to be protective [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.92, P=0.007)]. Compared with the largest complaint group, chest pain with an in-hospital fatality rate of 2.5%, there was a significantly increased risk of dying among those with stroke-like symptoms (OR 2.04, 95% CI 1.35-3.08, P=0.0007), dyspnoea (OR 1.95, 95% CI 1.27-3.00, P=0.002) or general disability (OR 1.81, 95% CI 1.17-2.79, P=0.008). The presenting complaint at the ED carries valuable information of the risk for in-hospital fatality in nonsurgical patients. This knowledge can be valuable in the prioritization between different patient groups in the process of initiating diagnostics and treatment procedures at the ED.


Purification, characterization and amino acid content of cholesterol oxidase produced by Streptomyces aegyptia NEAE 102.
There is an increasing demand on cholesterol oxidase for its various industrial and clinical applications. The current research was focused on extracellular cholesterol oxidase production under submerged fermentation by a local isolate previously identified as Streptomyces aegyptia NEAE 102. The crude enzyme extract was purified by two purification steps, protein precipitation using ammonium sulfate followed by ion exchange chromatography using DEAE Sepharose CL-6B. The kinetic parameters of purified cholesterol oxidase from Streptomyces aegyptia NEAE 102 were studied. The best conditions for maximum cholesterol oxidase activity were found to be 105 min of incubation time, an initial pH of 7 and temperature of 37 °C. The optimum substrate concentration was found to be 0.4 mM. The higher thermal stability behavior of cholesterol oxidase was at 50 °C. Around 63.86% of the initial activity was retained by the enzyme after 20 min of incubation at 50 °C. The apparent molecular weight of the purified enzyme as sized by sodium dodecyl sulphate-polyacryalamide gel electrophoresis was approximately 46 KDa. On DEAE Sepharose CL-6B column cholesterol oxidase was purified to homogeneity with final specific activity of 16.08 U/mg protein and 3.14-fold enhancement. The amino acid analysis of the purified enzyme produced by Streptomyces aegyptia NEAE 102 illustrated that, cholesterol oxidase is composed of 361 residues with glutamic acid as the most represented amino acid with concentration of 11.49 μg/mL. Taking into account the extracellular production, wide pH tolerance, thermal stability and shelf life, cholesterol oxidase produced by Streptomyces aegyptia NEAE 102 suggested that the enzyme could be industrially useful.


Distribution of monoamines in the central nervous system of the nudibranch gastropod, Hermissenda crassicornis.
The distribution of monoamines in the central ganglia of the nudibranch gastropod Hermissenda crassicornis was examined through the histological localization of both glyoxylic acid-induced fluorescence and serotonin-like immunoreactivity. Glyoxylic acid histochemistry revealed several clusters of catecholamine-containing cells which were located principally in the cerebropleural ganglia. One large unpaired catecholamine-containing cell was also located in the right pedal ganglion. Glyoxylic acid histochemistry and immunohistochemistry together revealed several serotonin-containing cells. The most prominent of these was a bilateral pair of cells (the metacerebral giants or MCG's) with somata located in the anterior lobes of the cerebropleural ganglia and each with a single large axon running through the ipsilateral cerebrobuccal connective to the buccal ganglia. Apart from the MCG's and a few smaller ones in the cerebropleural ganglia, most other serotonergic cells were located in the pedal ganglia. Among the serotonergic cells identified in the pedal ganglia was a single unpaired giant cell (LP1) located only on the left side. The neurites of LP1 projected through the cerebropleural ganglia to the contralateral pedal ganglion. Similarities in the distribution of monoamines in different gastropod species are discussed.


Psychological functioning of children in a battered women's shelter: a preliminary investigation.
Self-concept, anxiety level, and problem behavior of 65 child residents of a battered women's shelter were assessed using self-report measures and checklists completed by mothers, staff, and teachers. Findings included a below-average self-concept score for the preschool group, more aggressive behavior in school-age shelter boys than in girls, and a pervasive tendency for mothers to rate their children more negatively than did other observers.


[Effect of geniposide on serum IL-1beta and TNF-alpha of rheumatoid arthritis rats].
To study the effect of geniposide on serum IL-1beta and TNF-alpha levels of rheumatoid arthritis rats, as well as the mechanism of this drug. To establish an experimental rat model of type II collagen-induced arthritic (CIA). The inhibitory effects on paw edema were observed, and serum IL-1beta and TNF-alpha levels were determined in experimental rats. Compared with the model, geniposide delayed the starting time of right paw edema significantly, and the levels of serum IL-1beta and TNF-alpha were significantly decreased by geniposide at high dose or medium dose (P < 0.01). Geniposide can lower serum IL-1beta and TNF-alpha levels in rheumatoid arthritis rats. The effect may be close related to inhibitory development of rheumatoid arthritis by the agent.


Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic review.
Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or "selective" lymphadenectomy. Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required.


Proteomic analysis of hyperoxia-induced responses in the human choriocarcinoma cell line JEG-3.
Living cells exposed to changes in the surrounding oxygen tension, have the ability to adapt to the new environment through the regulatory effect of intracellular mediators. In an effort to identify important proteins that may be involved in the hyperoxic response, we performed proteomic analysis on the human choriocarcinoma cell line JEG-3, incubated under high oxygen tension (carbogen, 95% O2/5% CO(2)) or air (21% oxygen/5% CO(2)). We identified 13 protein spots that were significantly down-regulated (p < 0.05) in JEG-3 cells incubated under hyperoxic conditions compared to standard conditions. Ten of these spots were positively identified by matrix-assisted laser desorption/ionization time of flight-mass spectrometry as nine different proteins: Villin 2, tublin beta, profilin I, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, peroxiredoxin 1, neuroplypeptide h3, poly(rC)-binding protein 1 and cyclophilin A. These proteins have been implicated in regulating cytoskeletal structure, glycolysis, redox status, signal transduction, transcription and protein folding. The data obtained are consistent with the roles of these proteins in mediating cellular response to oxidative stress and in regulating cell proliferation and motility.


Sphingolipids and Lymphomas: A Double-Edged Sword.
Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.


Improved polarized light microscopic detection of gouty crystals via dissolution with formalin and ethylenediamine tetraacetic acid.
Conventional polarized light microscopy has been widely used to detect gouty crystals, but its limited sensitivity increases the risk of misidentification. In this study, a number of methods were investigated to improve the sensitivity of polarized light microscopy for the detection of monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD) crystals. We found that coating glass slides with poly-L-lysine, a positively charged polymer, improved the attachment of crystals to the glass surface, resulting in clearer crystal images compared to non-coated slides. Additionally, the sensitivity of detection was further enhanced by selective dissolution, in which 40% v/v formalin phosphate buffer was employed to dissolve MSUM crystals but not CPPD while 10% ethylenediamine tetraacetic acid (EDTA) was employed to dissolved CPPD but not MSUM. The other possible interferences were dissolved in both EDTA and formalin solution. These methods were successfully applied to detect gouty crystals in biological milieu, including spiked porcine synovial fluid and inflamed rat subcutaneous air pouch tissues.


Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring.
Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months' dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.


Bathing-induced seizures.
Two unusual patients with sensory-induced seizures are presented. The clinical approach and evolution of seizures induced by bathing in patients with and without accompanying epilepsy are discussed.


Mice with pulmonary tuberculosis treated with Mycobacterium vaccae develop strikingly enhanced recall gamma interferon responses to M. vaccae cell wall skeleton.
Whole heat-killed Mycobacterium vaccae is used as an immunotherapeutic agent in tuberculosis (TB), but the compound(s) that triggers its immunostimulatory ability is not known. Here, we show that among different subcellular fractions, the cell wall skeleton induced a prominent expression of gamma interferon in splenocytes from both non-TB and TB M. vaccae-treated mice.


Adaptation of yellow fever virus 17D to Vero cells is associated with mutations in structural and non-structural protein genes.
Serial passaging of yellow fever virus 17D in Vero cells was employed to derive seed material for a novel inactivated vaccine, XRX-001. Two independent passaging series identified a novel lysine to arginine mutation at amino acid 160 of the envelope protein, a surface-exposed residue in structural domain I. A third passage series resulted in an isoleucine to methionine mutation at residue 113 of the NS4B protein, a central membrane spanning region of the protein which has previously been associated with Vero cell adaptation of other mosquito-borne flaviviruses. These studies confirm that flavivirus adaptation to growth in Vero cells can be mediated by structural or non-structural protein mutations.


Pilonidal sinus: a claim for simple track incision.
Ninety-six patients treated surgically for pilonidal sinus were examined in a two-part study. In the first part, 36 patients were randomly allocated according to the surgical techniques employed: marsupialization, incision, and excision without primary closure. Healing times and recurrences a year after operation were studied. The healing times of patients treated by excision were longer in comparison with those treated by incision or marsupialization. The recurrence rates were similar for all techniques used. In the second part of the study 60 patients were randomly allocated according to times of returning to work. Twenty-nine of these patients returned to work before their wound healed; 31 resumed work a week after epithelization of the wound. The wounds healed more quickly in patients who started working before they were closed. Incision of the sinus track, carried out using local anesthesia in the outpatient clinic, allowed the patient to return to work without pain sooner.


Longitudinal changes in domains of physical activity during the transition from elementary school to high school in the U.S.
To describe patterns of age-related change in self-reported physical activity domains within a heterogeneous sample of boys and girls in the U.S. transitioning from elementary to high school. Prospective cohort study. Participants included n = 644 children recruited in 5th grade (10.5 ± 0.5 years old, 45 % female) who completed the Physical Activity Choices survey at least twice over 5 time points (5th, 6th, 7th, 9th and 11th grade). Participants' self-reported physical activities were categorized into organized and non-organized activities, and a comprehensive variable was created as the product of the total number of physical activities reported in the past 5 days, the number of days spent in each activity, and the total time spent in each activity. Descriptive statistics and growth curve models (controlling for covariates) for the total sample and by sex were examined for total, organized, and non-organized physical activities from ages 10 to 17. There was a significant age by gender interaction (p < 0.05) for time spent in non-organized physical activities. Specifically, both sexes had similar patterns of decline before age 13, while boys increased after age 13 and girls declined and then maintained. In contrast, boys and girls declined in organized physical activities from ages 10 to 17 (p < 0.001). We observed stark differences in the age-related change between organized and non-organized physical activities and marked differences in the patterns of non-organized physical activities between boys and girls. Future research should examine physical activity interventions that consider age-, sex-, and domain-specific physical activity options for youth.


Editorial: The Vanishing Value of Evidence-based Treatments: Is Our Mental Health Expertise Irrelevant?
The article in this issue of JAACAP by the CAMELS (Child/Adolescent Anxiety Multimodal Extended Long-term Study) study team, Peris et al.1, offers 2 very important contributions. Conveniently, the first contribution is also the stated purpose of this report: to present findings detailing the extent to which children and adolescents who previously participated (averaging 6.5 years previously) in the landmark Child and Adolescent Multimodal Study of Anxiety (CAMS) multisite randomized controlled trial (RCT)2 did or did not receive follow-up services. This is not a good-news story. By and large, over the 6-year follow-up, only 35% of the previous RCT-treated children and youth received "consistent" continuing services, either through medication or cognitive-behavioral therapy (CBT), despite ongoing issues of anxiety and significant impairment.


Noninvasive measurement of bladder pressure by controlled inflation of a penile cuff.
A noninvasive test providing reliable objective quantification of bladder pressure during the voiding cycle would make an important contribution to the management of lower urinary tract symptoms. We developed a new noninvasive test to measure bladder pressure in males based on controlled inflation of a penile cuff during voiding. We compared the new technique with simultaneous invasive bladder pressure measurement. We evaluated 7 volunteers and 32 patients. A conventional pressure flow study was performed first. The bladder was refilled, a penile cuff was fitted and after voiding commenced the cuff was inflated in steps of 10 cm. water every 0.75 seconds until urine flow was interrupted. The cuff was rapidly deflated, allowing flow to resume, and the cycle was repeated until the end of voiding. The flow rate was graphed against cuff pressure for each interruption cycle to determine the pressure at which flow was interrupted. This pressure was compared with simultaneous invasive isovolumetric bladder pressure. Invasive and noninvasive pressure measurements agreed well. Average cuff pressure at interruption of flow exceeded mean simultaneous isovolumetric bladder pressure plus or minus standard deviation by 14.5 +/- 14.0 cm. water. The new method provides noninvasive quantitative information on voiding bladder pressure in males. Further study is required to assess whether the technique can contribute to the management of lower urinary tract symptoms.


[Idiopathic aortic thrombosis in a full-term newborn infant].
A case of idiopathic aortic thrombosis in a term neonate is reported. Ultrasound examination led to diagnosis and an embolectomy was carried out. Literature data concerning etiology and treatment of neonatal aortic thrombosis are reviewed.


Antibody-dependent cell-mediated cytotoxicity against Epstein-Barr virus membrane antigen in African Burkitt's lymphoma.
Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.


Retinoic acid downregulates microRNAs to induce abnormal development of spinal cord in spina bifida rat model.
MicroRNAs have been found in the developing central nervous system, but little is known about their functions in development, especially in the abnormal development of spinal cord in spina bifida. To this end, we have studied the mechanism of microRNAs involved in the morphogenesis of the spinal cord in all-trans-retinoic acid (RA)-treated spina bifida rat fetus. Timed-pregnant rats were gavage-fed RA, and embryos were obtained on 13.5, 15.5, 17.5, and 19.5 days. MicroRNAs' expression profile was analyzed by Northern blot. In situ apoptosis detection and microRNA in situ hybridization methods on sections of paraffin-embedded tissues were employed to explore the mechanism. Administration of RA reduced the size of the spinal cord, probably as a consequence of increased cell death. There is a dramatic decrease in the expression of miR-9/9*, miR-124a and miR-125b, and Bcl2 and P53 as well in the sacral cord from E13.5 to E19.5 days post coitum. Our data showed that expression of these microRNAs was dysregulated in RA-treated spinal cord during embryonic development, suggesting that they may be involved in the development of the spinal cord.


Papillary cystic and solid tumour of the pancreas: report of a case and literature review.
The papillary cystic and solid tumour of the pancreas (PCSTP) is a rare primary neoplasm of unknown pathogenesis typically found in young women. PCSTP is a low-grade malignant tumour, which is often asymptomatic but it may present with abdominal pain. A 38 year old female patient who presented with one day history of epigastric pain was diagnosed as PCSTP. The patient was successfully treated with distal pancreatectomy. It is important to differentiate this tumour from other pancreatic tumours because, unlike malignant pancreatic tumours, this neoplasm does not usually metastasise and is amenable to cure after complete surgical resection. However, the cell origin and the aetiology of this tumour are not clear and further studies are warranted in its pathogenesis.


Failure of the Agility total ankle replacement system and the salvage options.
The Agility total ankle replacement system was the most commonly performed implant in the United States for more than 20 years and has undergone four generations and seven phases of improvement. Much attention has been placed on intraoperative complications, such as malleolar fracture; nerve or tendon injury; and incision healing-related problems, such as wound coverage and infection. However, it is the intermediate- and long-term complications (ie, aseptic osteolysis, subsidence, component loosening, and progressive malalignment) that require careful consideration, because the revision options remain limited. This article reviews the history of the Agility total ankle replacement system in detail, to understand the revision possibilities available.


Removal of Pb from a calcareous soil during EDTA-enhanced electrokinetic extraction.
Electrokinetic extraction has been tested to remove lead from an Algerian contaminated soil ([Pb] = 4.432 +/- 0.275 mg g(-1)) sited near a battery plant. The effect of EDTA at various concentrations (0.05-0.20 M) on the enhancement of lead transport has been studied by applying a constant voltage corresponding to a nominal electric field strength of 1 V cm(-1) (duration: 240 h). Results of contaminant distribution across the experimental cell have shown efficient transport of lead toward the anode despite the presence of calcite (25%) and the high acid/base buffer capacity of the soil. To avoid ligand loss, which would be anodically oxidized, the cell was modified by adding extra compartments and inserting cation exchange membranes (Neosepta CMX). Thus, simultaneous recovery of EDTA and lead from their chelated solutions has been made possible using the same set-up and by controlling fluids chemistry.


Inadequate receipt of ANC components and associated factors among pregnant women in Northwest Ethiopia, 2020-2021: a community-based cross-sectional study.
Women's health and pregnancy outcomes are directly depends on the extent of ANC components received during their ANC visits. There are limited information about the components of ANC and associated factors. Therefore, the aim of this study was to assess the magnitude of inadequate recipient of ANC components and associated factors in northwest Ethiopia. This is a community based cross sectional survey conducted in Dabat Demographic and health survey from December 10/2020 to January 10/2021 among women who gave birth within two years before the survey. This study applied a census method to identify and select eligible pregnant women. A structured and pretested questionnaire was used to collect the data. The data was entered into Epi-data version 3.1 and exported to STATA version 14 for analysis purpose. Adjusted Odds Ratio at 95% confidence interval was used to show the association between dependent and independent variables. Statistical significance was declared at a P value less than 0.05. A total of 871 pregnant women were identified from the survey and included in this study. Overall, 96.67% (95% CI: 95.24, 97.67) had not get adequate (all components) ANC. The components of ANC services were increased from 3.35 to 32.34%, 2.52 to 46.33% 1.96 to 55.8%, 2.31 to 46.53%, 3.54 to 55.75%, 2.46 to 44.62%, 1.18 to 45.96%, and 2.45 to 54.6% for tetanus toxoid Vaccine, HIV/AIDS testing and counseling, danger sign, place of delivery, deworming, iron folic acid, family planning, and breast feeding counseling, from first ANC visit to fourth ANC visit, respectively. Rural residence (AOR = 4.89, 95% CI: 1.21, 19.86), and less than four number of ANC visit (AOR = 5.15, 95% CI: 2.06, 12.86) were significantly associated with inadequate uptake of ANC components. Only three in hundred pregnant women were received adequate ANC components in the study area. Rural residence and less than four number of ANC visit were factors significantly associated with inadequate ANC uptake. Therefore, the district health department managers and program implementers need to train the health care providers about the components of ANC. As well, increasing community and facility awareness of WHO recommendations on ANC visits focusing on rural women is needed.


Genome sequencing of a single cell of the widely distributed marine subsurface Dehalococcoidia, phylum Chloroflexi.
Bacteria of the class Dehalococcoidia (DEH), phylum Chloroflexi, are widely distributed in the marine subsurface, yet metabolic properties of the many uncultivated lineages are completely unknown. This study therefore analysed genomic content from a single DEH cell designated 'DEH-J10' obtained from the sediments of Aarhus Bay, Denmark. Real-time PCR showed the DEH-J10 phylotype was abundant in upper sediments but was absent below 160 cm below sea floor. A 1.44 Mbp assembly was obtained and was estimated to represent up to 60.8% of the full genome. The predicted genome is much larger than genomes of cultivated DEH and appears to confer metabolic versatility. Numerous genes encoding enzymes of core and auxiliary beta-oxidation pathways were identified, suggesting that this organism is capable of oxidising various fatty acids and/or structurally related substrates. Additional substrate versatility was indicated by genes, which may enable the bacterium to oxidise aromatic compounds. Genes encoding enzymes of the reductive acetyl-CoA pathway were identified, which may also enable the fixation of CO2 or oxidation of organics completely to CO2. Genes encoding a putative dimethylsulphoxide reductase were the only evidence for a respiratory terminal reductase. No evidence for reductive dehalogenase genes was found. Genetic evidence also suggests that the organism could synthesise ATP by converting acetyl-CoA to acetate by substrate-level phosphorylation. Other encoded enzymes putatively conferring marine adaptations such as salt tolerance and organo-sulphate sulfohydrolysis were identified. Together, these analyses provide the first insights into the potential metabolic traits that may enable members of the DEH to occupy an ecological niche in marine sediments.


Long Non-Coding RNA Cancer Susceptibility 9 (CASC9) Up-Regulates the Expression of ERBB2 by Inhibiting miR-193a-5p in Colorectal Cancer [Retraction].
[This retracts the article DOI: 10.2147/CMAR.S234620.].


Effect of chronic consumption of blackberry extract on high-fat induced obesity in rats and its correlation with metabolic and brain outcomes.
Flavonoids have been presented as potential protectors against metabolic and cognitive dysfunction. However, mechanisms underlying these 'claims' have not been sufficiently explored. To analyse the effect of long-term supplementation with blackberry extract (BE) in the context of a high-fat or a standard diet, Wistar rats were divided into 4 groups (n = 6) fed with a standard or a high-fat diet, with or without BE supplementation at 25 mg per kg body weight per day. A high-fat diet significantly impaired glucose tolerance and increased body weight, caloric ingestion, very-low-density lipoprotein, triglycerides and cholesterol. Furthermore, it was observed that a high-fat diet increased dopamine content in the prefrontal cortex and decreased brain derived neurotrophic factor (BDNF) levels both in the prefrontal cortex and in plasma. BE supplementation only affected some of these aspects. BE slightly improved glucose metabolism and significantly decreased levels of lactate, independent of diet. BE decreased levels of BDNF and also interacted with the dopaminergic system, increasing dopamine turnover in the striatum, and reverting dopamine content induced by a high-fat diet in the prefrontal cortex. This study shows that, despite some particular benefits of anthocyanin supplementation, some long-term effects may not be desirable and further studies are needed to optimize ingestion conditions.


Trajectories of depression, anxiety and stress among adults during the COVID-19 pandemic in Southern Switzerland: the Corona Immunitas Ticino cohort study.
Using longitudinal data from Southern Switzerland we assessed ten-month temporal trajectories of moderate to severe depression, anxiety and stress among adults after the first pandemic wave and explored differences between sociodemographic and health status groups. This was a population-based prospective cohort study. Participants were 732 (60% women) adults aged 20-64 years who completed the Depression, Anxiety and Stress Scale on a monthly base since August 2020 until May 2021, as part of the Corona Immunitas Ticino study based on a probability sample of non-institutionalized residents in Ticino, Southern Switzerland. Prevalence of moderate to severe depression increased from 7.5% in August 2020 to 12.5% in May 2021, anxiety increased from 4.8% to 8.1% and stress increased from 5.5% to 8.8%. A steeper increase in poor mental health was observed between October 2020 and February 2021. Men had a lower risk for anxiety (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.95) and stress (OR = 0.61, 95% CI = 0.44-0.95) than women. Suffering from a chronic disease increased the risk for depression (OR = 1.82, 95% CI = 1.12-2.96), anxiety (OR = 2.38, 95% CI = 1.44-3.92) and stress (OR = 1.87, 95% CI = 1.14-3.08). The differences between these groups did not vary over time. In a representative Swiss adult sample, prevalence of moderate to severe depression, anxiety and stress almost doubled in the course of ten months following the end of the first pandemic wave in spring 2020. Women and participants with pre-existing chronic conditions were at a higher risk of poor mental health.


Differential expression of E-cadherin and beta catenin in primary and metastatic Wilms's tumours.
The E-cadherin-catenin adhesion complex is crucial for intercellular adhesiveness and maintenance of tissue architecture. Its impairment is associated with poorly differentiated phenotype and increased invasiveness of carcinomas. To evaluate E-cadherin, beta catenin, gamma catenin, and ezrin expression and its relation to histopathological features of primary and metastatic Wilms's tumours. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin, beta catenin, gamma catenin, and ezrin in primary and metastatic Wilms's tumours. Western blotting was used to determine polypeptide size and expression of E-cadherin and beta catenin in Wilms's tumours compared with normal kidney. Moderate expression of E-cadherin was found mainly in cytoplasm and occasionally cell membranes of dysplastic tubules, whereas low expression was seen in cytoplasm of blastemal cells. Primary and metastatic tumours showed moderate to high beta catenin expression in blastemal and epithelial cells, with predominantly membranous and cytoplasmic staining. Occasional nuclear staining was noted in metastatic tumours. Low to high gamma catenin and ezrin expression was seen in cytoplasm of blastemal and epithelial cells of primary and metastatic tumours. Higher amounts of 92 kDa beta catenin were detected in tumours than in normal kidney. Low expression of 120 kDa E-cadherin was seen in moderately differentiated tumours, whereas expression was lacking in poorly differentiated tumours. Compared with primary tumours, metastatic tumours showed lower expression of E-cadherin and gamma catenin, with nuclear staining for beta catenin. Low E-cadherin was associated with poorly differentiated tumours. These results suggest that abnormal expression of adhesion proteins correlates with the invasive and metastatic phenotype in Wilms's tumours.


Theoretical investigations on the mechanistic pathway of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines.
The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determined and reaction identified by IRC calculations. The results show that thermal rearrangements occur in three ways. Firstly, the transition state TS 1 in which a hydrogen atom of methyl groups migrates from primary carbon to oxygen of amid group to give the N-methallylamide 2. The second is via the transition state TS 2 in which the attack of oxygen to the tertiary carbon yields the oxazoline 3. The third is via the transition state TS 3 in which a hydrogen migrate from the secondary carbon to oxygen to give the vinylamide 4. In order to get insights into the factors determining the exact nature of its interactions with electrophiles, the application of reactivity parameters derived from density functional theory in a local sense, in particular the softness and Fukui function, to interpret and predict the mechanisms of the thermal decomposition of the N-acyl-2,2-dimethylaziridines 1, has been discussed.


Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model.
We examined the role of IL-6 in the temporal development of cardiac ischemia-reperfusion injury employing a closed-chest I/R model. Infarction, local and systemic inflammation, neutrophil infiltration, coagulation and ST elevation/resolution were compared between wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice after 1 h ischemia and 0, ½, 3, and 24 h reperfusion. IL-6 deficiency reduced infarct size at 3 h reperfusion (28.8 ± 4.5 % WT vs 17.6 ± 2.5 % IL-6(-/-)), which reduction persisted and remained similar at 24 h reperfusion (25.1 ± 3.0 % WT vs 14.6 ± 4.4 % IL-6(-/-)). Serum Amyloid A was reduced at 24 h reperfusion only (57.5 ± 4.9 WT vs 24.8 ± 5.6 ug/ml IL-6(-/-) mice). Cardiac cytokines (IL-6, IL-1β and TNFα) peaked at 3 h reperfusion, but IL-1β and TNFα levels were unaffected by IL-6 deficiency. Significant neutrophil influx was only detected at 24 h reperfusion and was similar for WT and IL-6(-/-). Tissue factor peaked at 24 h reperfusion, whereas fibrin/fibrinogen peaked at 3 h reperfusion and was completely resolved at 24 h reperfusion; both coagulation factors were unaltered by IL-6 deficiency. Prolonged ST elevation was observed during ischemia that completely resolved for both genotypes at early reperfusion. The data suggest that, in the absence of major surgical intervention, IL-6 contributes to the development of infarct size in the early phase of reperfusion; this contribution did not depend on neutrophil influx, IL-1β and TNFα, tissue factor and fibrin.


Characterization of polysaccharide-protein complexes by size-exclusion chromatography combined with three detectors.
Two water-soluble samples (TM1 and TM2) were extracted from Pleurotus tuber-regium using 0.9% aqueous NaCl at 20 and 80 degrees C to obtain relatively low molecular mass fractions. The chemical structure of TM1 was analyzed to be a branched heteropolysaccharide-protein complex, and the sugar moiety was mainly beta-(1-->6)-, beta-(1-->4)-, and beta-(1-->3)-linked glucan containing galactose and mannose. TM2 was a branched polysaccharide-protein complex, and the sugar moiety was mainly beta-(1-->6)-, beta-(1-->4)-, and beta-(1-->3)-linked glucan. Preparative size-exclusion chromatography (SEC) and analytical SEC combined with three detectors were used to detect the TM1 and TM2 samples, confirming that the proteins were bonded to the polysaccharides. Furthermore, analytical SEC combined with online laser light scattering, differential refractive index detector, and UV to determine the components, weight-average molecular mass (M(w)) and chain conformation of the samples. The relatively low exponent values (nu) of S(2)(z)(1/2)=k(nu)M(w)(nu) for the samples in 0.15M aqueous NaCl at 25 degrees C suggested that TM1 and TM2 existed in compact sphere conformation in the aqueous solution. This work provided valuable information on the structure and chain conformation characterization of the polysaccharide-protein complex having relatively low M(w).


[Effect of nootropil on oxidative phosphorylation in the brain of rats with ischemic myocardial necrosis].
In experiments on rats the formation of ischemic myocardial necrosis was shown to be followed by dissociation of the processes of oxidation and phosphorylation in mitochondria of the cerebral hemispheres. Administration of nootropil to the animals in the acute period prevented the occurrence of these disturbances.


Patient Reported Kneeling Ability in Fixed and Mobile Bearing Knee Arthroplasty.
Kneeling is an important function of the knee joint required for many daily activities. Bearing type is thought to influence functional outcome following UKA and TKA. Self-reported kneeling ability was recorded in 471 UKA and 206 TKA patients with fixed or mobile bearing implants. Kneeling ability was recorded from the Oxford Knee Score question 7. The self-reported ability to kneel was similar in patients with fixed and mobile bearing UKA implants following surgery. In TKA, greater proportions of patients were able to kneel in the fixed compared to the mobile bearing groups up to two years after surgery indicating that self-reported kneeling ability is enhanced in fixed compared to mobile bearing TKA.


Destructive sterile vesicoureteral reflux observed over a 12-year period.
The evolution over a 12-year follow-up period from only slightly damaged kidneys to end-stage renal disease due to sterile ureteral reflux is reported.


Branched nonreversed saphenous vein graft for complex renal artery stenosis.
Use of recently developed instrumentation for venous valvotomy allows rapid construction of a branched, nonreversed saphenous vein graft. This technique was applied in a patient with renovascular hypertension and branch renal artery occlusive disease.


Phospholipid reverse micelles as a milieu of an enzyme reaction in an apolar system.
Alkaline phosphatase was entrapped in reverse micelles formed in n-heptane with surfactants (bis(2-ethylhexyl)sodium sulfosuccinate, phosphatidylcholine, phosphatidylethanolamine, or phosphatidic acid) and water. The entrapped enzyme could express its activity in the reverse micelles of the above surfactants only when the substrate, p-nitrophenylphosphate, was within the reverse micelles of bis(2-ethylhexyl)sodium sulfosuccinate. The optimum pH of activity in the reverse micelles was higher by about one pH unit than that determined in bulk water. Regardless of water content (mol water/mol surfactant = 10 or 14.8), the Km value was about 30 mM, while Vmax at the higher water content (14.8) was 2-4 times greater than that at 10. Activation energy of the reaction depended on the kind of reverse micelles. Differences in carbon chain length of solvents showed no effect on the kinetic properties of the enzyme.


Posttreatment nonalcoholic fatty liver disease fibrosis scores for predicting liver-related complications in patients with chronic hepatitis C receiving direct-acting antiviral agents.
Patients with chronic hepatitis C (CHC) have a higher prevalence of hepatic steatosis and dyslipidaemia than healthy individuals. We analysed noninvasive fibrosis assessments, especially nonalcoholic fatty liver disease (NAFLD)-related noninvasive fibrosis tests, for predicting liver-related complications and hepatocellular carcinoma (HCC) occurrence in patients with CHC. This retrospective study enrolled 590 consecutive patients with CHC having a sustained virologic response (SVR) to direct-acting antiviral agent (DAA) therapy. The NAFLD fibrosis score (NFS) exhibiting the highest value of area under the receiver operating characteristic curve (AUROC) was selected for comparison with the fibrosis-4 index (FIB-4). Of the 590 patients, 188 had metabolic syndrome. A multivariate Cox regression analysis identified total bilirubin at 3 or 6 months after DAA therapy (PW12), NFS at PW12 (hazard ratio [HR]: 2.125, 95% confidence interval [CI]: 1.058-4.267, p = .034) and alpha-fetoprotein (AFP) at PW12 (HR: 1.071, 95% CI: 1.005-1.142, p = .034) as the independent predictors of liver-related complications in all patients. In patients with metabolic syndrome, NFS and AFP values at PW12 were independent predictors of liver-related complications and HCC occurrence. Time-dependent NFS AUROC values at PW12 for 1-, 2- and 3-year liver-related complications were higher than NFS values at baseline in patients with metabolic syndrome. NFS at baseline or PW12 is a more effective predictor of liver-related complications than FIB-4 values in all patients. NFS at PW12 may be a useful predictor of liver-related complications and HCC development in patients with CHC with an SVR to DAA therapy, especially in those with metabolic syndrome.


Assessment of the extended Koopmans' theorem for the chemical reactivity: Accurate computations of chemical potentials, chemical hardnesses, and electrophilicity indices.
The extended Koopmans' theorem (EKT) provides a straightforward way to compute ionization potentials and electron affinities from any level of theory. Although it is widely applied to ionization potentials, the EKT approach has not been applied to evaluation of the chemical reactivity. We present the first benchmarking study to investigate the performance of the EKT methods for predictions of chemical potentials (μ) (hence electronegativities), chemical hardnesses (η), and electrophilicity indices (ω). We assess the performance of the EKT approaches for post-Hartree-Fock methods, such as Møller-Plesset perturbation theory, the coupled-electron pair theory, and their orbital-optimized counterparts for the evaluation of the chemical reactivity. Especially, results of the orbital-optimized coupled-electron pair theory method (with the aug-cc-pVQZ basis set) for predictions of the chemical reactivity are very promising; the corresponding mean absolute errors are 0.16, 0.28, and 0.09 eV for μ, η, and ω, respectively.


Refractory systemic lupus erythematosus with chylous effusion successfully treated with sirolimus: a case report and literature review.
Chylous effusion is a rare manifestation of systemic lupus erythematosus (SLE). When it does occur in SLE, it is generally well treated with standard pharmacologic or surgical measures. We present a decade of management in a case of SLE with lung affliction and development of refractory bilateral chylous effusion and pulmonary arterial hypertension (PAH). In the first years, the patient was treated under a Sjogren syndrome diagnose. After few years, her respiratory condition worsened due to chylous effusion and PAH. Immunosuppression therapy (methylprednisolone) was reintroduced, and vasodilator therapy commenced. With this, her cardiac function remained stable, but respiratory function continuously worsened despite several therapy trials with different combinations of immunosuppressant (glucocorticoids, resochin, cyclophosphamide and mycophenolate mofetil). On top of pleural effusion worsening, the patient developed ascites and severe hypoalbuminaemia. Even though albumin loss was stabilized with monthly octreotide applications, the patient remained respiratory insufficient and in need of continuous oxygen therapy. At that point, we decided to introduce sirolimus on top of glucocorticoids and mycophenolate mofetil therapy. Her clinical status, radiological finding, and lung function gradually improved and she became respiratory sufficient at rest. The patient remains in our follow-up and has been stable on given therapy for over 3 years despite overcoming a severe COVID-19 pneumonia in 2021. This case adds to the body of evidence of sirolimus effectiveness in patients with refractory systemic lupus and is, to our best knowledge, the first case to report its successful application in a patient with SLE and refractory chylous effusion.


Localization of stress protein-70 in ovine corpora lutea during prostaglandin-induced luteolysis.
Accumulation of heat shock (stress) protein-70 (HSP-70) was assessed in corpora lutea of sheep obtained after in vivo administration of a luteolytic dose of prostaglandin (PG) F2 alpha. A quantitative immunofluorescence technique was used to localize inducible HSP-70 production to specific cell-types. The number and intensity of immunostained large luteal cells increased within 2 h of injection of PGF2 alpha. A drop in luteal progesterone concentrations (functional regression) was not manifested until 4 h post-treatment. A dramatic increase in intensely-stained mononuclear leukocytes was observed in luteal tissues at 16 h, when glandular weights had begun to diminish (structural regression). Stress proteins could mediate intracellular protein processing and cell-surface autoimmune mechanisms underlying luteal regression.


Efficacy and safety of a new testosterone-in-adhesive matrix patch applied every 2 days for 1 year to hypogonadal men.
To study long-term efficacy and safety of a testosterone-in-adhesive matrix patch, delivering 4.8 mg of testosterone daily. Randomized, open label, multicenter 1-year study. 224 hypogonadal patients were included. 188 received 2 patches of 60 cm2 every 48 h and 36 patients had IM testosterone enanthate injection every 3 weeks. T, bioavailable T (BT), DHT, E2, LH, FSH and SHBG and clinical symptom scores (AMS and MSF-4) were assessed at 3, 6 and 12 months. In the patch group, T serum levels were above 3 ng/mL in 85% of patients and remained stable over time. BT, DHT and E2 levels were restored within physiological range. BT/T ratio varied from 20 to 70%. In the IM group, the percentages of "normalized" patients appeared to be lower, although the two groups cannot be adequately compared due to the kinetic profile of T following IM administration, resulting in greater variations of serum T levels, blood samplings occurring randomly at time of peak, trough, or in between. A significant correlation was found between T, BT and the MSF-4 changes. BT levels were significantly related to total AMS score. PSA values showed a mean (S.D.) increase of 0.13 (0.38), 0.23 (0.79) and 0.30 (1.47)ng/mL at weeks 14, 27 and 53, respectively. The patch was well tolerated with no negative impact either on lipid profile, or red blood cells. Administration site reactions occurred in 35 patients (18.8%). Adhesiveness was good (>or=75%) in >90% patients over the 1 year application period. Two 60 cm2 patches, allowed constant physiological levels of sexual hormones over time. This new patch was well tolerated, easy to use, well accepted by the patients and displayed a very good adhesiveness. Clinical efficacy was more related to BT than to T.


A novel ansamycin, naphthomycin K from Streptomyces sp.
One novel ansamycin, namely naphthomycin K, together with two known naphthomycins A and E, were isolated from the commensal strain Streptomyces sp. CS of the medicinal plant Maytenus hookeri. Their structures were elucidated by the analysis of NMR and MS data. Naphthomycin K showed evident cytotoxicity against P388 and A-549 cell lines, but no inhibitory activities against Staphylococcus aureus and Mycobacterium tuberculosis.


Factors influencing time to operating room in children presenting with post-tonsillectomy hemorrhage.
We aimed to evaluate factors associated with time to return to OR in children presenting with post-tonsillectomy hemorrhage to a tertiary children's hospital. Retrospective study of pediatric patients presenting to a single institution from January 2012 to January 2020, with post-tonsillectomy hemorrhage (PTH) requiring surgical intervention for control of bleeding. Correlation, univariate, and multivariate analysis were conducted. Of 15,984 tonsillectomies performed at our institution during the study period, 144 required return to the OR for bleeding control, in addition to 15 other children whose tonsillectomy had been performed at an outside institution. Mean time to the OR was 119.7 min (SD 101.5) in the morning, 77.4 min (SD 60.6) in the afternoon, 55.6 min (SD 34.8) in the evening, and 49.4 min (SD 26.4) overnight (ANOVA p < 0.0001). The mean hemoglobin decline from pre-to post-tonsillectomy was 1.3 g/dl (SD 1.7). Primary hemorrhages had a mean time to OR of 62.39 min (SD 63.42) while secondary hemorrhages mean time to OR was 85.54 min (SD 76.21) (p = 0.0064). There was no significant difference in time to OR among race/ethnicity (p = 0.928), insurance status (p = 0.359), weekday (p = 0.557), surgeon seniority (p = 0.8104) or by hemoglobin drop (p = 0.2773). When controlling for each of these variables, multiple linear regression showed that only time of day had significant correlation with time to OR (p = 0.0003). At a tertiary children's hospital, patients presenting with PTH requiring revision surgery waited the longest to get to the OR in the morning versus all other times of day. These results can aid in individualization of anticipatory guidance in order to reduce morbidity and mortality from complications requiring revision in the operating room.


Expression of the third component of complement, C3, in regenerating limb blastema cells of urodeles.
In this study we have shown that complement component C3 is expressed in the regenerating tissue during urodele limb regeneration. C3 was expressed in the dedifferentiated regeneration blastema and in the redifferentiated limb tissues in the axolotl, Amblystoma mexicanum, and in Notophthalmus viridescens. This expression was verified by immunofluorescent staining using an Ab against axolotl C3 and by in situ hybridization with an axolotl C3 cDNA probe. In the early stages of regeneration C3 appeared to be equally present in all mesenchymal cells and in the wound epithelium, whereas in the later stages it was mainly expressed in the differentiating muscle cells. Since no expression was seen in the developing limb, it appears that the C3 expression was specific to the regeneration process. We then demonstrated by hybridization experiments that a blastema cell line of myogenic origin expresses C3. All these findings implicate C3 in the dedifferentiation process and may indicate a new role for this molecule in muscle differentiation.


Community-acquired acinetobacter pneumonia.
Acinetobacter calcoaceticus var anitratus, a nonfermentative grampnegative bacillus, has been infrequently reported as a cause of community-acquired pneumonia. In this paper we describe the course of six recent patients with community-acquired, bacteremic pneumonia due to this organism and review the six previously reported cases. Our experience suggests this organism is a more common cause of community-acquired pneumonia than previously thought. Acinetobacter pneumonia occurs in older persons with chronic disease, especially alcoholism. It is a fulminant illness with respiratory distress, hypoxemia, leukopenia and shock. Chest roentgenograms reveal a lobar or bronchopneumonic infiltrate which often becomes bilateral within 24 hours of admission to the hospital. Pleural effusions are common. The mortality rate is 43 per cent. Factors that predict a fatal outcome are granulocytopenia, empyema and therapy with inappropriate antibiotics. Therapy with appropriate antibiotics, especially carbenicillin and an aminoglycoside, increases survival.


Perceived discrimination and smoking among rural-to-urban migrant women in China.
Smoking may be a coping mechanism for psychosocial stress caused by discrimination. We conducted a cross-sectional survey of rural-to-urban migrant women working as restaurant/hotel workers (RHWs) and those working as sex workers (FSWs) in 10 Chinese cities to investigate whether perceived discrimination is associated with smoking. We interviewed RHWs at medical examination clinics and FSWs at entertainment venues. Modified Poisson regression was used to estimate prevalence ratios. Of the 1,696 RHWs and 532 FSWs enrolled, 155 (9.1%) and 63 (11.8%) reported perceived discrimination, respectively. Perceived discrimination was independently associated with ever tried smoking (prevalence ratio [PR], 1.71; 95% confidence interval [CI], 1.31-2.23) and current smoking (PR, 2.52; 95% CI, 1.32-4.79) among RHWs and ever tried smoking (PR, 1.36; 95% CI, 1.16-1.61) and current smoking (PR, 1.63; 95% CI, 1.28-2.06) among FSWs. Perceived discrimination is associated with higher prevalence of smoking among rural-to-urban migrant women in China.


Regional sensitivity to verapamil in ventricular myocardium.
The effects of verapamil (0.1-4.0 micrograms/ml) on transmembrane action potential configuration was examined in various regions of the normal cat left ventricular endocardium. Surface electrograms showed that the sequence of activation of anterior papillary muscle fibers was from the base of the muscle to its apex, while overlying Purkinje fibers were activated in the opposite direction. Action potential duration in basal muscle fibers was relatively unaffected by verapamil, while cells at the tip of the papillary muscle showed increased slope in phase 2 and a more rapid rate of early repolarization. Regional sensitivity to verapamil may reflect disparate patterns of endocardial activation, and could influence the effectiveness of the drug against ventricular arrhythmias.


Pulsed electromagnetic fields inhibit human osteoclast formation and gene expression via osteoblasts.
Pulsed electromagnetic fields (PEMFs) can be effective in promoting the healing of delayed union or nonunion fractures. We previously reported that PEMF (Spinal-Stim® by Orthofix, Inc., Lewisville, TX) stimulated proliferation, differentiation and mineralization of rat calvarial osteoblastic cells in culture. In the present work we investigated the effects of PEMF (Physio-Stim® by Orthofix, Inc., Lewisville, TX) on human bone marrow macrophages (hBMMs) differentiated to osteoclasts. PEMF had striking inhibitory effects on formation of osteoclasts from hBMMs from both younger and older women. There were significantly greater changes in gene expression as ascertained by RNAseq from cells from older women. Interestingly, all of the genes identified by RNAseq were upregulated, and all were genes of mesenchymal or osteoblastic cells and included members of the TGF-β signaling pathway and many extracellular matrix proteins, as well as RANKL and osteoprotegerin, indicating the mixed nature of these cultures. From these results, we suggest that PEMF can inhibit osteoclast formation via action on osteoblasts. Thus, PEMF may be very effective for bone mass maintenance in subjects with osteoporosis.


Anesthetic considerations and surgical caveats for awake airway surgery.
The evolution of novel techniques for the treatment of laryngeal pathology has led to a significant expansion of the role of diagnostic assessment and the range of laryngeal procedures performed. These procedures typically benefit from an anesthetic approach that diverges from a standard general endotracheal or laryngeal mask airway-based inhalational anesthetic. The shared airway, need for intraoperative assessment of vocal cord function, risk of airway fire, and desire for rapid emergence and discharge are all important factors. In this article the authors undertake a collaborative anesthesia-surgical discussion of anesthetic management for airway procedures that are optimally performed with a spontaneously breathing, cooperative patient. An overview of pharmacologic approaches to airway anesthesia and cooperative sedation, followed by a discussion on the surgical requirements and anesthetic goals of commonly performed procedures, are presented.


Local erythematous dermatitis after intravenous docetaxel.
We report the case of a patient who developed a local skin eruption over the vein following intravenous infusion of docetaxel at 4-week intervals. The skin lesions were limited to an area of the forearm proximal to the site of infusion. They appeared 1 week after the infusion and were diagnosed as erythema multiforme (mixed-type) based on the histological findings.


Transformation and toxicity of environmental contaminants as influenced by Fe containing clay minerals: a review.
Clay minerals are ubiquitous in soil and sediments, and play important roles in environmental processes. Virtually all clay minerals contain some Fe, either in the crystal structure or adsorbed at the surface of the clay minerals, which could promote many reactions on the clay minerals. The interaction between Fe containing clay mineral and its surrounding contaminants would greatly affect the transformation and toxicity of the contaminants. While it is certain that the Fe plays important roles in the fate of the contaminants, relative qualitative and quantitative assessment of these processes is limited. Based on the overall toxicity variation, this paper reviews the active areas of the researches on the interactions between Fe containing clay mineral and contaminants, and provides perspectives for future work.


Effect of initial calorie intake via enteral nutrition in critical illness: a meta-analysis of randomised controlled trials.
Guidelines support the use of enteral nutrition to improve clinical outcomes in critical illness; however, the optimal calorie and protein intake remains unclear. The purpose of this meta-analysis was to quantitatively analyze randomised controlled trials with regard to clinical outcomes related to varying calorie and protein administration in critically ill adult patients. We searched Medline, EMBASE, and Cochrane databases to identify randomised controlled trials that compared the effects of initially different calorie and protein intake in critical illness. The risk ratio (RR) and weighted mean difference with 95% confidence intervals (CI) were calculated using random-effects models. The primary endpoint was mortality; secondary endpoints included infection, pneumonia, gastrointestinal intolerance, hospital and intensive care unit lengths of stay, and mechanical ventilation days. In the eight randomised controlled trials that enrolled 1,895 patients there was no statistical difference between the low-energy and high-energy groups in mortality (RR, 0.90; 95% CI, 0.71 to 1.15; P = 0.40), infection (RR, 1.09; 95% CI, 0.92 to 1.29; P = 0.32), or the risk of gastrointestinal intolerance (RR, 0.84; 95% CI, 0.59 to 1.19; P = 0.33). In subgroup analysis, the low-energy subgroup, fed 33.3 to 66.6% of goal energy, showed a lower mortality than the high-energy group (RR, 0.68; 95% CI, 0.51 to 0.92; P = 0.01). The improvements in mortality and gastrointestinal intolerance were absent when calorie intake was >66.6% of goal energy in the low-energy group. High-energy intake combined with high-protein intake reduced the infections (RR, 1.25; 95% CI, 1.04 to 1.52; P = 0.02); however, when the daily protein intake was similar in both groups, a high-energy intake did not decrease the infections. No statistical differences were observed in other secondary outcomes. This meta-analysis indicates that high-energy intake does not improve outcomes and may increase complications in critically ill patients who are not malnourished. Initial moderate nutrient intake (33.3 to 66.6% of goal energy), compared to high energy, may reduce mortality, and a higher protein intake combined with high energy (≥ 0.85 g/kg per day) may decrease the infection rate. However, the contribution of energy versus protein intake to outcomes remains unknown.


New homeopathic medicines: use of modern drugs according to the principle of similitude.
The homeopathic method is based on the application of the principle of therapeutic similitude (similia similibus curentur), using medicines that cause effects similar to the symptoms of disease in order to stimulate the reaction of the organism against disturbances. Such vital, homeostatic or paradoxical reaction of the organism can be scientifically explained on the basis of the rebound effect of modern drugs. This article presents the conclusion of a study aiming at a method to use modern drugs with homeopathic criteria. Adverse effects as catalogued in United States Pharmacopoeia Dispensing Information Drug monographs were collected. A homeopathic materia medica and repertory comprising 1251 modern drugs to be employed according to the principle of therapeutic similitude was developed. Besides supplying a basis for homeopathy as a medical rationale related to scientific pharmacology, this study makes available a method that may broaden the scope of intervention of homeopathy in present day diseases.


Arteriovenous differences across human adipose and forearm tissues after overnight fast.
Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re-esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm.


Quantitative Analysis of Bile Acid with UHPLC-MS/MS.
Bile acids are important end products of cholesterol metabolism, having been shown to serve as signaling molecules and intermediates between the host and the gut microbiota. Here we describe a robust and accurate method using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the quantification of bile acids in stool/cecal and tissue samples.


Interferometric null test of a deep parabolic reflector generating a Hertzian dipole field.
We report on interferometric characterization of a deep parabolic mirror with a depth of more than five times its focal length. The interferometer is of Fizeau type; its core consists of the mirror itself, a spherical null element, and a reference flat. Because of the extreme solid angle produced by the paraboloid, the alignment of the setup appears to be very critical and needs auxiliary systems for control. Aberrations caused by misalignments are removed via fitting of suitable functionals provided by means of ray tracing simulations. It turns out that the usual misalignment approximations fail under these extreme conditions.


Use of Doppler ultrasonography for selection of recipients in embryo transfer programs in horses.
We aimed to evaluate the impact of corpus luteum (CL) and uterine characteristics accessed by B-mode and Color-Doppler ultrasonography in recipient mares at the time of embryo transfer (ET) on pregnancy outcomes. Recipient mares (n = 110), between days 3-9 after spontaneous ovulation, received a fresh embryo. Immediately before ET, the reproductive system was assessed by transrectal palpation for the following parameters: uterine tone (0-3), CL echogenicity (0-6), CL type (homogeneous, trabecular or anechoic center), luteal area (cm2), uterine echogenicity (0-3), uterine edema (0-3), luteal blood perfusion (0-100%) and uterine blood perfusion (1-4). Additionally, a blood sample was collected by puncture of the jugular vein for plasma P4 dosage. Retrospectively, recipients were classified according to the luteal area (small [≤ 6 cm2] or large [> 6 cm2]), luteal blood perfusion (low [≤ 55%] or high [> 55%]), and plasma concentration of P4 (low ≤ 9.98 ng/mL or high > 9.98 ng/mL). Pregnancy diagnosis was performed at 12 and 30 days of gestation. Luteal blood perfusion was significantly higher (P = 0.04) in pregnant recipients (n = 83) than in non-pregnant recipients (n = 27). Overall P/ET was higher (P ≤ 0.02) in mares with high luteal blood perfusion and high P4. Luteal blood perfusion was the most adequate significant (P = 0.01) predictor of pregnancy compared with the luteal area and plasma P4 concentration. Only luteal blood perfusion showed a linear (P = 0.03) and cubic (P = 0.004) effect on P/ET. In conclusion, CL blood perfusion determined by color-Doppler can be used in real-time to select recipients with the greatest chance of maintaining pregnancy in equine ET programs.


Complete Genome Sequence of an Environmental Bacillus cereus Isolate Belonging to the Bacillus anthracis Clade.
We report here the complete genome sequence of a Bacillus cereus isolate identified in a soil sample from Namibia. This isolate is closely related to the B. anthracis clade. While the plasmids (500 and 12 kb) carry no detectable B. anthracis virulence gene, the large plasmid shares a 50-kb continuous region similar to plasmid pXO1.


Immunohistochemical localization of neuropeptide FF-like in the brain of the turtle: relation to catecholaminergic structures.
A previous study in the lizard Gekko gecko has revealed that neuropeptide FF (NPFF, a neuropeptide involved in nociception, cardiovascular regulation, and endocrine function) is widely distributed throughout the brain and spinal cord. Although the distribution of NPFF immunoreactivity shares many features with that found in other vertebrates, it was noted that Gekko shared more features with anamniotes in terms of number of cell groups, more elaborate networks of fibers, and lack of colocalization with catecholamines, than with mammals. To assess the primitive or derived character of these features, NPFF and tyrosine hydroxylase (TH) antibodies have been applied to the brain and spinal cord of the turtle, Pseudemys scripta elegans, which belongs to a different radiation of reptiles. As in Gekko, major NPFF-ir cell groups were found in the diagonal band nucleus of Broca and in the hypothalamus, whereas additional cells were identified in the anterior olfactory nucleus, lateral and dorsal cortices, dorsal ventricular ridge, and the intergeniculate leaflet formation. Notable differences are the presence of NPFF-ir cells in the medial cortex and striatum of Pseudemys, which are lacking in Gekko. On the other hand, no NPFF-ir cells could be detected in the septal region and dorsal horn of the spinal cord in Pseudemys. Double staining with NPFF and TH antibodies revealed an intimate relationship between NPFF-ir and TH-ir structures but colocalization could not be established. In conclusion, the distribution of NPFF in the brain of Pseudemys has corroborated previous results in Gekko, but also revealed some notable species differences.


Who is Overdosing? An Updated Picture of Overdose Deaths From 2008 to 2015.
To determine the role of opioids in drug overdose deaths in Allen County, Indiana between January 1, 2008, and December 31, 2015. File review of 418 overdose deaths was performed using Indiana State Department of Health death certificates available through the Allen County Coroner's Office. Data from autopsy and toxicology reports and coroner-requested prescribing data from Indiana's Prescription Monitoring Program were reviewed. Cause of death and available data were analyzed to identify patterns and trends related to overdose deaths. Four hundred eighteen drug overdose deaths were identified (336 accidental, 66 intentional, and 16 undetermined). Mean age was 42.5 years, 88.5% were Caucasian, and 68.7% were employed. The majority of deaths occurred at a place of residence (71.4%) and with other people present (57.5% of the time). Depression was the most common comorbidity identified. The most common drug classes identified by toxicology were opioids, followed by benzodiazepines. Significant increases in both heroin (35% of deaths in 2015 versus 8.2% in 2013) and fentanyl (30% of deaths in 2015 versus 2.2% in 2011) were observed. Drug overdose continues to be a significant cause of death in Allen County. The majority of deaths were accidental and in relatively young, employed individuals. Prevention and awareness strategies should be encouraged, given that the majority of overdose deaths occurred at a place of residence with other people frequently present. Additional concerns about patterns of drug use were confirmed with marked increases in both heroin and fentanyl contributing to overdose deaths in the latter part of the study.


Evidence for two pathways of protein kinase C induction of 2ar expression: correlation with mitogenesis.
2ar is a cDNA clone of an mRNA that is inducible by 12-0-tetradecanoylphorbol-13-acetate (TPA) in mouse JB6 epidermal cells. This mRNA is stably induced in confluent cells but only transiently induced in subconfluent cells; the elevated level of 2ar mRNA in TPA-treated cells appears to be the result of enhanced transcription (Smith and Denhardt: Journal of Cellular Biochemistry 34:13-22, 1987). Phorbol dibutyrate, teleocidin, and aplysiatoxin, which activate protein kinase C and are also tumor promoters, are shown here to induce 2ar to the same extent as TPA at both cell densities. The increased expression by TPA was prevented by cycloheximide and by H7, a specific inhibitor of protein kinase C. Epidermal growth factor, platelet-derived growth factor, and the nonphorbol promoter diethylhexylphthalate were more effective inducers in confluent than in subconfluent cultures. All-trans retinoic acid, dexamethasone and fluocinolone acetonide, inhibitors of tumor promotion, diminished 2ar induction in both acetonide, inhibitors of tumor promotion, diminished 2ar induction in both confluent and subconfluent cells. In TPA-treated subconfluent cultures indomethacin produced a slight inhibition, whereas difluoromethyl ornithine potentiated the induction. In TPA-treated confluent cultures, in contrast, indomethacin enhanced 2ar mRNA levels and difluoromethyl ornithine was inhibitory. We conclude that the protein kinase C-mediated induction of 2ar expression is controlled by different pathways in subconfluent cultures and confluent cultures, indicative of apparent changes in the regulation of gene expression as proliferating cells become quiescent.


Analysis of the variability of airborne particulate matter with prevailing meteorological conditions across a semi-urban environment using a network of low-cost air quality sensors.
The concentrations of fine and coarse fractions of airborne particulate matter (PM) and meteorological variables (wind speed, wind direction, temperature and relative humidity) were measured at six selected locations in Ile Ife, a prominent university town in Nigeria using a network of low-cost air quality (AQ) sensor units. The objective of the deployment was to collate baseline air quality data and assess the impact of prevailing meteorological conditions on PM concentrations in selected residential communities downwind of an iron smelting facility. The raw data obtained from OPC-N2 of the AQ sensor units was corrected using the RH correction factor developed based k-Kohler theory. This PM (corrected) fast time resolution data (20 s) from the AQ sensor units were used to create daily averages. The overall mean mass concentrations for PM2.5 and PM10 were 213.3, 44.1, 23.8, 27.7, 20.2 and 41.5 μg/m3 and; 439.9, 107.1, 55.0, 72.4, 45.5 and 112.0 μg/m3 for Fasina (Iron-Steel Smelting Factory, ISSF), Modomo, Eleweran, Fire Service, O.A.U. staff quarters and Obafemi Awolowo University Teaching and Research Farm (OAUTRF), respectively. PM concentration and wind speed showed a negative exponential distribution curve with the lowest exponential fit coefficient of determination (R2) values of 0.08 for PM2.5 and 0.03 for PM10 during nighttime periods at Eleweran and Fire service sites, respectively. The relationship between PM concentration and temperature gave a decay curve indicating that higher PM concentrations were observed at lower temperatures. The exponential distribution curve for the relationship between PM concentration and relative humidity (RH) showed that PM concentrations do not vary for RH < 80 % while stronger relationship was noticed with higher PM concentration for RH > 80 % for both day and nighttime. The performances of the MLR model were slightly poor and as such not too reliable for predicting the concentration but useful for improving predictive model accuracy when other variables contributing to the variability of PM is considered. The study concluded that the anthropogenic and industrial activities at the smelting factory contribute significantly to the elevated PM mass concentration measured at the study locations.


Tumor size is not a criterion for resection during the management of giant hemangioma of the liver.
Liver hemangiomas are the most common benign liver tumors. The management of giant (≥5 cm) hemangioma of the liver remains controversial. The aim of this study was to assess the influence of tumor size on postoperative outcomes after hepatectomy in patients with giant hemangioma of the liver. Patients who were subjected to resection because of giant liver hemangioma between December 2006 and July 2012 were grouped by largest tumor size: 5-10 cm (group A) and 10-15 cm (group B). All patients underwent detailed preoperative assessments. Clinicopathologic features were analyzed, and univariate and multivariate analyses were used to determine risk factors that correlated independently with any complication, as well as the intraoperative red blood cell transfusion requirement. Long-term outcomes were assessed with a median follow-up of 56 months. One hundred and ninety patients, mean age 46 years, were included. The 146 patients with tumors 5-10 cm in size were compared with the remaining 44 patients with tumors 5-10 cm in size. The differences in postoperative morbidity (29.86 vs. 41.30%, P=0.150) and duration of hospitalization (11.06±7.02 vs. 12.17±7.74, P=0.465) between group A and group B did not reach statistical significance. Operation time, blood loss, and transfusion volume of group B were greater than those of group A. No perioperative deaths occurred and no recurrences were registered during follow-up in both groups. The results of univariate and multivariate analysis showed that diameter was not an independent risk factor of postoperative complications and intraoperative red blood cell transfusion. Giant hemangiomas should be monitored regularly. Asymptomatic tumors 5-10 cm in diameter can be managed conservatively even though they grow. When necessary, surgical treatment can be well justified because of low morbidity and mortality.


Increase in dance imprecision with decreasing foraging distance in the honey bee Apis mellifera L. is partly explained by physical constraints.
Honey bee foragers communicate the direction and distance of both food sources and new nest sites to nest mates by means of a symbolic dance language. Interestingly, the precision by which dancers transfer directional information is negatively correlated with the distance to the advertised food source. The 'tuned-error' hypothesis suggests that colonies benefit from this imprecision as it spreads recruits out over a patch of constant size irrespective of the distance to the advertised site. An alternative to the tuned-error hypothesis is that dancers are physically incapable of dancing with great precision for nearby sources. Here we revisit the tuned-error hypothesis by studying the change in dance precision with increasing foraging distance over relatively short distances while controlling for environmental influences. We show that bees indeed increase their dance precision with the increase in foraging distance. However, we also show that dance performed by swarm-scouts for a nearby (30 m) nest site, where there could be no benefit to imprecision, are either without or with only limited directional information. This result suggests that imprecision in dance communication is caused primarily by physical constraints in the ability of dancers to turn around quickly enough when the advertised site is nearby.