Ginkgo biloba extract improves coronary artery circulation in patients with coronary artery disease: contribution of plasma nitric oxide and endothelin-1.
In patients with coronary artery disease (CAD), coronary blood flow is usually impaired due to imbalanced vasoactive substances such as nitric oxide (NO) and endothelin-1 (ET-1). The study was designed to test the effects of Ginkgo biloba extract (GBE) on the distal left anterior descending coronary artery (LAD) blood flow and plasma NO and ET-1 levels. Eighty CAD patients were randomly assigned to GBE (n = 42) and control (n = 38) groups. The LAD blood flow was assessed non-invasively using Doppler echocardiography at baseline and after 2 weeks. GBE treatment demonstrated a significant improvement in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with controls (14.61 +/- 4.51% vs 0.67 +/- 2.66%, 9.03 +/- 4.81% vs 0.34 +/- 2.67% and 14.69 +/- 5.08% vs 0.68 +/- 3.00%, respectively, p < 0.01). NO was increased by 12.42% (p < 0.01), whereas ET-1 was decreased by 5.82% (p < 0.01). The NO/ET-1 ratio was increased by 19.47% (p < 0.01). A linear correlation was confirmed between the percentage change in LAD blood flow and in NO, ET-1 or NO/ET-1 ratio following GBE treatment. The results suggest that GBE treatment in CAD patients led to an increase of LAD blood flow, which might at least be related partly to the restoration of the delicate equilibrium between NO and ET-1.


Long-Term Efficacy and Safety of Rituximab Versus Tacrolimus in Children With Steroid Dependent Nephrotic Syndrome.
In the Rituximab for Relapse Prevention in Nephrotic Syndrome (RITURNS) trial, we demonstrated superior efficacy of single-course rituximab over maintenance tacrolimus in preventing relapses in children with steroid dependent nephrotic syndrome (SDNS) during a 1-year observation. Here we present the long-term outcomes of all 117 trial completers, who were followed up for another 2 years. Relapsing patients in the rituximab arm received a second course of rituximab, either with (n = 44) or without mycophenolate mofetil (MMF) cotreatment (n = 15). In the tacrolimus arm, second line rituximab monotherapy was initiated after relapses (n = 32) or electively (n = 24). All 12-month relapse-free patients in the rituximab arm relapsed in the second postexposure year, resulting in similar median relapse-free survival times in the 2 trial arms (62 vs. 59 weeks). Second line rituximab in the tacrolimus arm was less effective than first-line therapy in patients switched to rituximab following a relapse (relapse-free survival 55 vs. 63 weeks, P < 0.01). B-cell counts 6 months post-rituximab predicted relapse risk both for first and second line therapy. MMF cotreatment yielded much improved 2-year relapse-free survival as compared to rituximab monotherapy (67% vs. 9%, P < 0.0001). Higher grade 2 adverse event rates were observed post-rituximab versus on tacrolimus (0.87 vs. 0.53 per year). The superior therapeutic effect of rituximab in SDNS vanishes during the second year post-exposure. Rituximab appears to yield longer remission when applied as first line as compared to second line therapy. Maintenance MMF following rituximab induces long-term disease remission.


Break out of the box: how to add value to the security function.
Opportunities to create programs that enhance the value of the security function are present now and will be in the future, according to the author, who illustrates a number of ways the resourceful security practitioner can add to his department's reputation and his organization's bottom line.


Antioxidant enzymes in blood of patients with Friedreich's ataxia.
Increased generation of reactive oxygen species and mitochondrial dysfunction may underlie the pathophysiology of Friedreich's ataxia, the most common inherited ataxia, due to GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Because iron overload would cause oxidative stress in Friedreich's ataxia, we investigated the enzyme antioxidant system in the blood of 14 patients by determining superoxide dismutase, glutathione peroxidase, and glutathione transferase catalytic activities. We also studied the glutathione S-transferase genotype polymorphism in order to evaluate its possible influence on enzyme activity. Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia and 21 age matched healthy subjects. Antioxidant enzyme determinations were spectrophotometrically assayed using specific substrates; the glutathione S-transferase genotype polymorphism was analysed by endonuclease restriction mapping of exon 5 and 6 amplification products. There was a significant elevation of the superoxide dismutase/glutathione peroxidase activity ratio (0.037 (0.01) v 0.025 (0.008) of controls) and an 83% rise of glutathione transferase specific activity (0.22 (0.1) v 0.12 (0.03) nmol/min/mg protein) in blood of patients with Friedreich's ataxia than in the controls. The genotype polymorphism of glutathione S-transferase enzyme did not show any relevant differences when compared to that of healthy subjects. Data show an impairment in vivo of antioxidant enzymes in patients with Friedreich's ataxia and provide evidence of an increased sensitivity to oxidative stress, supporting a consistent role of free radical cytotoxicity in the pathophysiology of the disease.


Detection of the sour-rot pathogen Geotrichum candidum in tomato fruit and juice by using a highly specific monoclonal antibody-based ELISA.
Geotrichum candidum is a common soil-borne fungus that causes sour-rot of tomatoes, citrus fruits and vegetables, and is a major contaminant on tomato processing equipment. The aim of this work was to produce a monoclonal antibody and diagnostic assay for its detection in tomato fruit and juice. Using hybridoma technology, a cell line (FE10) was generated that produced a monoclonal antibody belonging to the immunoglobulin class M (IgM) that was specific to G. candidum and the closely related teleomorphic species Galactomyces geotrichum and anamorphic species Geotrichum europaeum and Geotrichum pseudocandidum in the G. geotrichum/G. candidum complex. The MAb did not cross-react with a wide range of unrelated fungi, including some likely to be encountered during crop production and processing. The MAb binds to an immunodominant high molecular mass (> 200 kDa) extracellular polysaccharide antigen that is present on the surface of arthroconidia and hyphae of G. candidum. The MAb was used in a highly specific enzyme-linked immunosorbent assay (ELISA) to accurately detect the fungus in infected tomato fruit and juice. Specificity of the ELISA was confirmed by sequencing of the internally transcribed spacer (ITS) 1-5.8S-ITS2 rRNA-encoding regions of fungi isolated from naturally-infected tomatoes.


GABAA receptor immunoreactivity in the white matter.
Using immunohistochemical methods with polyclonal antibodies directed against a specific sequence of the beta 1-subunit of the GABAA receptor, we found strong immunoreactivity in the white matter of cat brain. The immunopositive products were present primarily on processes of glial cells, especially astrocytes. Immunoreactivity appeared also on the cell bodies of astrocytes and on the cytoplasmic membranes of neurons. The abundant immunostaining in the white matter suggests that (1) GABAA receptors are present on glial cells in vivo, (2) GABAA receptors may be localized on non-synaptic membranes in the white matter and (3) activation of GABAA receptors may have some trophic effects on preservation of the structure and functional properties of the white matter.


Intra-oral cone radiation therapy for selected carcinomas of the oral cavity.
A study of 101 patients with early carcinomas of the oral cavity, T1 and T2, treated by external cobalt 60 beam and/or intra-oral cone (IOC) radiation therapy between 1964 through 1980 was made. The two year disease-free survival rate, including surgical salvage, was 88% and the local control rate was 85%. The incidence of radiation complications, i.e. soft tissue ulceration and/or osteoradionecrosis, was 14% and varied with various tumor sites and radiation doses delivered. The present review shows that local control and radiation complications are closely related to radiation doses and varies with different tumor sites of the oral cavity. Radiation therapy dosages expressed in terms of TDF values for these lesions are herein recommended. With proper selections of lesions arising from the oral cavity, combined external beam and IOC radiation therapy has been found extremely efficacious in achieving good local tumor control and high survival rates with excellent cosmetic and functional results and minimum radiation sequelae.


Synthesis of ABO histo-blood group type I and II antigens.
The ABO histo-blood group system is one of the most clinically important antigen families. As part of our overall goal to prepare the entire set of the A, B and H type I-VI antigens for a range of biochemical investigations, we report herein the synthesis of the type I and II antigens with a 7-octen-1-yl aglycone. This linker was chosen to facilitate not only the future conjugation of the antigens to a protein or solid support but also the synthesis of the H type I and II octyl glycosides for enzyme kinetic studies.


A thiolate ligand on a cytochrome P-450 mimic permits the use of simple environmentally benign oxidants for biomimetic steroid hydroxylation in water.
Manganese porphyrin systems carrying cyclodextrin binding groups can regioselectively and stereoselectively hydroxylate bound steroid substrates, using iodosobenzene as oxidant, but hydrogen peroxide and other simple oxidants such as sodium hypochlorite are not effective in water. Thiol ligands were then added to the catalyst, both covalently attached and hydrophobically bound, and with these ligands hydrogen peroxide was now an effective oxidant.


A new catheter system for permanent percutaneous nephrostomy.
A new catheter system is described for permanent percutaneous nephrostomy. The system allows the rapid, single stage placement of a large diameter drainage catheter. The technique avoids several problems associated with previous methods of percutaneous nephrostomy.


Gastric polyposis due to multiple hyperplastic adenomatous polyps.
Four cases of gastric polyposis in which the multiple polyps were hyperplastic adenomatous polyps are presented with endoscopic and histologic description. The multiple hyperplastic adenomatous polyps in our cases showed more diffuse involvement of specific regions of the stomach than is usual with papillary adenomatous polyps. Hyperplastic adenomatous polyps have a low potential for malignancy, and it is suggested that they may be followed by periodic observation rather than fulguration or removal.


Pain coping strategies for children with arthritis.
To present information on pain management strategies for children with juvenile idiopathic arthritis (JIA). The second author developed a manual to present pain management strategies to children. The use of the manual was pilot-tested with a group of children with JIA. Telephone interviews were used to gather information on implementation of pain management strategies. Children were able to implement the pain management strategies. Children reported a reduction in daily pain experiences related to JIA when using the pain management strategies. The pain management strategies were successful as an adjunctive intervention for short-term pain management. Pain symptoms related to JIA can severely limit children's participation in daily activities. Further study on how children use pain management strategies to improve their involvement in daily activities will provide useful clinical information.


Cervical Shirodkar cerclage may be the treatment modality of choice for cervical pregnancy.
Our objective was to evaluate the use of cervical suture in cervical pregnancy. All cases of cervical pregnancy diagnosed and treated in the gynaecological department at the Sheba Medical Center between 1994-2000 were included in the study. Eight such cases were diagnosed. The first four cases were treated medically. The last four cases (the study group) of cervical pregnancy, including one case of heterotopic pregnancy, were treated successfully with placement of Shirodkar cerclage. Cervical cerclage may be considered as the treatment of choice in cases of cervical pregnancies. It may be the only therapy in cases of heterotopic pregnancies (intrauterine and cervical pregnancy).


Granulofilamentous meningioma.
A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.


Can physical exercise induce an effective fibrinolysis?
The study examined serum fibrin(ogen) degradation products (FDP/fdp) after short and prolonged exercise, before and after training, in young and elderly subjects. Six of 15 well-trained soccer players demonstrated an increase of FDP/fdp after a short graded maximal treadmill test. In 12 elderly subjects short maximal exercise produced no increase of FDP/fdp. However, in most of these subjects an exhaustive work load was not reached. Three of 16 moderately trained young subjects exhibited a small FDP/fdp increase after 45 minutes of submaximal exercise and in 3 of 10 participants an elevation of FDP/fdp was found after a 3 h-running test. Immediately after the race there was a significant (p less than 0.001) increase of fragment D, measured by an enzyme immunoassay. During a second 3 h-race after an 8 week physical training program, the post-exercise FDP/fdp and fragment D increase was slightly enhanced. Plasma fibrinogen was significantly (p less than 0.05) elevated on the fourth day after the 3 h-race before but not after the training program. In conclusion intense and/or prolonged physical exercise caused only a modest increase of FDP/fdp. Physical training seems only minimally to affect this response. It is speculated that in the trained subject, daily exercise-induced fibrinolytic activation might be more relevant to the risk of thrombotic or atherosclerotic disease than a higher absolute resting or post-exercise fibrinolytic level compared with the untrained.


Low-frequency coding variants at 6p21.33 and 20q11.21 are associated with lung cancer risk in Chinese populations.
Genome-wide association studies have successfully identified a subset of common variants associated with lung cancer risk. However, these variants explain only a fraction of lung cancer heritability. It has been proposed that low-frequency or rare variants might have strong effects and contribute to the missing heritability. To assess the role of low-frequency or rare variants in lung cancer development, we analyzed exome chips representing 1,348 lung cancer subjects and 1,998 control subjects during the discovery stage and subsequently evaluated promising associations in an additional 4,699 affected subjects and 4,915 control subjects during the replication stages. Single-variant and gene-based analyses were carried out for coding variants with a minor allele frequency less than 0.05. We identified three low-frequency missense variants in BAT2 (rs9469031, c.1544C>T [p.Pro515Leu]; odds ratio [OR] = 0.55, p = 1.28 × 10(-10)), FKBPL (rs200847762, c.410C>T [p.Pro137Leu]; OR = 0.25, p = 9.79 × 10(-12)), and BPIFB1 (rs6141383, c.850G>A [p.Val284Met]; OR = 1.72, p = 1.79 × 10(-7)); these variants were associated with lung cancer risk. rs9469031 in BAT2 and rs6141383 in BPIFB1 were also associated with the age of onset of lung cancer (p = 0.001 and 0.006, respectively). BAT2 and FKBPL at 6p21.33 and BPIFB1 at 20q11.21 were differentially expressed in lung tumors and paired normal tissues. Gene-based analysis revealed that FKBPL, in which two independent variants were identified, might account for the association with lung cancer risk at 6p21.33. Our results highlight the important role low-frequency variants play in lung cancer susceptibility and indicate that candidate genes at 6p21.33 and 20q11.21 are potentially biologically relevant to lung carcinogenesis.


Tackling the rise in canine fertility clinics.
Georgina Mills discusses calls for action to tackle the growing issue of unregulated canine fertility clinics in the UK.


The feeding biology of a species-rich genus of rainforest grasshoppers (Rhachicreagra, Orthoptera, Acrididae) : II. Foodplant preference and its relation to speciation.
1. Two geographically adjoining but allopatric and altitudinally disjunct species (nothra and anchidiphalara) of the forest grasshopper genus Rhachicreagra were compared for food plant preferences in the laboratory. It has been shown that both are oligophagous and that their natural diets are markedly different. Both were offered the same 8 foodplants in a matrix of 2-way choice experiments. These plants included all important constituents of the natural diets of both species. 2. The resultant preference rank order was virtually identical for the two species, suggesting that the proportions of the different plants in the natural diet are determined principally by their relative availability. 3. The only major differences between the rank orders of the two species arise from the fact that both show an increased preference (relative to the other species) for the commonest foodplant in their own habitat. Indirect evidence suggests that this is the result of evolutionary change, not of conditioning during the lifetime of the individual. 4. There is no suggestion that host plant switching has played any significant role in speciation within the genus.


Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives.
The base-catalyzed reaction of benzoyl acetone 1 with phenyl isothiocyanate yields the non-isolable intermediate 2. Treatment of 2 with dilute HCl afforded the corresponding thiocarbamoyl derivative 3. Reaction of the intermediate 2 with phenacyl bromide, ethyl bromoacetate, chloroacetonitrile, chloroacetyl chloride, bromodiethyl malonate and chloroacetone afforded the corresponding thiophene derivatives 5, 8, 15 and 17. The thiocarbamoyl derivative 3 reacts with arylazophenacyl bromide and/or hydrazine hydrate to afford the corresponding thiadiazole and pyrazole derivatives 20a-c and 22, respectively. These new synthesized compounds show generally a moderate molluscicidal activity to Biomphalaria alexandrina snails.


Pathogenic Specialization of Venturia nashicola, Causal Agent of Asian Pear Scab, and Resistance of Pear Cultivars Kinchaku and Xiangli.
Scab caused by Venturia nashicola is one of the most serious diseases of Asian pears, including Japanese pear (Pyrus pyrifolia var. culta) and Chinese pears (P. bretschneideri and P. ussuriensis). Breeding scab-resistant pear cultivars is essential to minimize fungicide use and development of fungicide resistance. A survey of pathogenic specialization in V. nashicola is needed to ensure durable scab resistance in cultivated pears. V. nashicola race 1, 2, and 3 isolates, each differing in pathogenicity to Japanese pear cultivar Kousui and Asian pear strain Mamenashi 12, have been reported in Japan. In this study, isolates collected from scabbed pears in China and Taiwan were classified as V. nashicola based on conidial size and mating ability. However, various isolates had pathogenicity distinct from races 1, 2, and 3 according to tests on seven differential host genotypes of pear cultivars from Japan (Kousui and strain Mamenashi 12), China (Jingbaili, Yali, Linyuli, and Nanguoli), and Taiwan (Hengshanli). These new races were designated as races 4 to 7. Progenies characteristic of race 3 isolates were produced using a cross between race 1 and race 2 isolates, suggesting the possible role of sexual recombination in the emergence of novel races. Japanese pear cultivar Kinchaku and Chinese P. sinkiangensis 'Xiangli' (a Korla fragrant pear grown in China) did not show visible symptoms after inoculation with any of the seven races. Broad scab resistance in Kinchaku and Xiangli makes them a promising genetic resource for resistance breeding programs.


HARC as an open-shell strategy to bypass oxidative addition in Ullmann-Goldberg couplings.
The copper-catalyzed arylation of unsaturated nitrogen heterocycles, known as the Ullmann-Goldberg coupling, is a valuable transformation for medicinal chemists, providing a modular disconnection for the rapid diversification of heteroaromatic cores. The utility of the coupling, however, has established limitations arising from a high-barrier copper oxidative addition step, which often necessitates the use of electron-rich ligands, elevated temperatures, and/or activated aryl electrophiles. Herein, we present an alternative aryl halide activation strategy, in which the critical oxidative addition (OA) mechanism has been replaced by a halogen abstraction-radical capture (HARC) sequence that allows the generation of the same Cu(III)-aryl intermediate albeit via a photoredox pathway. This alternative mechanistic paradigm decouples the bond-breaking and bond-forming steps of the catalytic cycle to enable the use of many previously inert aryl bromides. Overall, this mechanism allows access to both traditional C-N adducts at room temperature as well as a large range of previously inaccessible Ullmann-Goldberg coupling products including sterically demanding ortho-substituted heteroarenes.


Primary non-Hodgkin lymphoma of prostate presenting as benign prostatic hyperplasia.
A case of primary non-Hodgkin lymphoma of the prostatic gland is reported. The patient presented with a classic picture of benign prostatic hyperplasia. Review of the literature disclosed about 300 reported cases. Much controversy and confusion exists in the classification of non-Hodgkin lymphoma. The two current classifications are presented, and management of this condition is reviewed.


Effect of extracorporeal shock waves on callus formation during bone lengthening.
The effects of extracorporeal shock waves (ESWs) on callus formation during bone lengthening were studied in 25 female Japanese white rabbits. Bone lengthening of 9.8 mm was obtained over 2 weeks using the Orthofix M-100 bone fixator. ESWs were applied 3 weeks after surgery. Pins were removed 7 weeks after surgery, and specimens were prepared after the animals were killed at 9 and 24 weeks. The shock wave setting used was 0.42 mJ/mm(2) with a pulse interval of 2 Hz; 3000 shots each were applied to the central and peripheral areas. The specimens were evaluated using radiography, bone mineral density (BMD) measured by dual energy absorptiometry (DXA), and a three-point bending test to evaluate mechanical strength. Histological examination was performed on the lengthened portion. Radiographs and histological observations revealed no apparent fractures in nonlengthening tibias at the shock wave energy densities used. Radiographic observations revealed no apparent differences between the control group and the ESW group. BMD measurements by DXA revealed significantly increased bone mass in the ESW group 9 weeks after surgery. At 24 weeks after surgery the mean BMD had decreased to 25% and 15% of the values at 9 weeks in the control and ESW groups, respectively. The three-point bending test revealed no significant differences between the groups. Histological observations revealed significant capillary formation and osteoblasts and chondrocytes in the bone marrow as well as bridging of newly formed trabeculae 2 weeks after the bone was lengthened. At 4 weeks after treatment, observations included parts of the lengthened portion with no cortex or immature bone. At 9 weeks after surgery, cortex formation and a normal medullary cavity were clearly observed in the control group, whereas observations in the treated group included areas of the lengthened portion with no cortex and formation of immature trabecular structures and increased cancellous bone in the center of the lengthened portion. At 24 weeks after surgery, more prominent cortex formation and fatty marrow were observed in the ESW group than in the control group.


Utility of intraocular endoscope for lacrimal canaliculi and sac examination.
Intraocular endoscope was used as a dacryoendoscope, and its observations and performance in lacrimal drainage system (LDS) are reported. The Endo Optiks (Little Silver, New Jersey, USA), an intraocular endoscope (modified with customized sheath), was used for LDS visualization in ten normal adults and five patients with lacrimal disorders. We were able to capture high-definition images of lacrimal canaliculi and sac in all normal adults. Smooth whitish canalicular mucosa with lumen could be appreciated in all normal individuals. Common canaliculus showed variable folds among individuals and reddish lacrimal sac mucosa could be appreciated with great details. In patients with canalicular obstruction, site of obstruction was presented as whitish gray area with no visible lumen, which could be opened up precisely with trephination. No false passage was formed in any of the cases. One of the cases had membranous canalicular obstruction, which was opened with probe itself. Nasolacrimal duct could not be examined due to the shorter length of the probe. Intraocular endoscope can be used as high-resolution dacryoendoscope for visualization of lacrimal canaliculi and sac.


Genome-Wide Identification and Expression of MAPK Gene Family in Cultivated Strawberry and Their Involvement in Fruit Developing and Ripening.
Studies on many plants have shown that mitogen-activated protein kinases (MAPKs) are key proteins involved in regulating plant responses to biotic and abiotic stresses. However, their involvement in cultivated strawberry development and ripening remains unclear. In this study, 43 FaMAPK gene family members were identified in the genome of cultivated strawberry (Fragaria × ananassa), phylogenetic analysis indicated that FaMAPKs could be classified into four groups. Systematic analysis of the conserved motif, exon-intron structure showed that there were significant varieties between different groups in structure, but in the same group they were similar. Multiple cis-regulatory elements associated with phytohormone response, and abiotic and biotic stresses were predicted in the promoter regions of FaMAPK genes. Transcriptional analysis showed that all FaMAPK genes were expressed at all developmental stages. Meanwhile, the effect of exogenous ABA and sucrose on the expression profile of FaMAPKs was investigated. Exogenous ABA, sucrose, and ABA plus sucrose treatments upregulated the expression of FaMAPK genes and increased the content of endogenous ABA, sucrose, and anthocyanin in strawberry fruits, suggesting that ABA and sucrose might be involved in the FaMAPK-mediated regulation of strawberry fruit ripening. Based on the obtained results, MAPK genes closely related to the ripening of strawberries were screened to provide a theoretical basis and support for future research on strawberries.


Determination of CYP2C19 phenotype in black Americans with omeprazole: correlation with genotype.
Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype. This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic. Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications. Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for phenotype determination. Identification of CYP2C19m1 genotypes were performed with use of the polymerase chain reaction. Results were obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker). Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m1/m1) in exon 5 of CYP2C19. Twenty-eight of the extensive metabolizers were heterozygous (m1/wt) and the remaining 70 were homozygous (wt/wt). No side effects were reported. The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects. Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype.


An evaluation of residue features as correlates of voice disorders.
Two experiments were conducted to assess the correlations of residue features with some perceptual properties of voice disorders. First, 90 samples of the vowel /a/ produced by patients with various vocal pathologies were analyzed to obtain the residue features, and severity judgments of these vowel samples were obtained. The results of linear multiple regression analysis indicated that the features were highly correlated with the severity ratings. Second, an attempt was made to correlate the residue features with voice qualities. The features were calculated for the vowel /a/ produced by patients with vocal nodules, vocal fold paralysis, and vocal polyps and by normal talkers. Each vowel sample was rated on ten scales of voice quality. The results revealed high correlations among the quality scales so that discrete subject groups could not be formed. Thus, residue features may be useful in assessing the degree of vocal impairment, but their use as correlates of voice quality must await further research.


Wilms tumor in Africa: A systematic review of management challenges and outcome in two decades (2000-2019).
We performed a systematic review to highlight trends in management and outcome of Wilms tumor (WT) in Africa in the past two decades (2000-2019). Twenty-seven studies involving 2250 patients were analyzed. Overall, barring regional variations, 57.7% of the cases presented with advanced disease, 57.3% completed planned treatment, and survival was 56.5%. The publications in the two decades did not show significant differences in proportions of cases with advanced disease, completion of treatment rate, and cases lost to follow up. However, significantly more cases received preoperative chemotherapy, and survival improved in the last decade (2010-2019) compared to the earlier decade (2000-2009). Survival of WT in Africa might have improved in the last decade, but challenges of delayed presentation and abandonment of treatment have persisted. Measures that will encourage early access to expert care as well as improve on treatment compliance may further improve survival of WT in Africa.


Hepatic effects of chlorpropamide: inhibition of glucagon-stimulated gluconeogenesis in perfused livers of fasted rats.
In perfused livers of rats fasted for 24 h, glucagon (5 x 10(-10) M) significantly elevated tissue and perfusate levels of cyclic AMP and caused a twofold increase in glucose formation from lactate. Chlorpropamide (0.8 x 10(-3) M) consistently blocked these effects. Measurements of metabolic intermediates suggest that chlorpropamide may inhibit gluconeogenesis by antagonizing the action of glucagon on the phosphoenolpyruvate cycle. In the experiments described, chlorpropamide did not lower hepatic ATP concentration or energy charge, and exerted its effects at perfusate concentrations comparable to serum concentrations reported in patients on maintenance doses of the drug.


Challenges in the transition to independent radiation oncology practice and targeted interventions for improvement.
Numerous radiation oncology residents and junior attendings have identified common weaknesses in residency training that hinder the transition from training to independent practice. Recurrent themes include not only general autonomy but also proficiency in technical skills, such as treatment plan review and image verification, and nontechnical skills, such as leadership, mentorship, and education. While multiple strategies to address these deficiencies have been investigated, many are not widely available or may be difficult to implement. We aim to summarize the frequently cited challenges in the transition to independent radiation oncology practice as well as the pertinent interventions that have been explored.


[A rapid and simple method for the qualitative and quantitative determination of hexapropymate in biological fluids and organs (author's transl)].
The method is based mainly on the extraction of the substance by a small volume of organic solvent from an alkaline medium containing a fairly important amount of inorganic salt. The extract is then subjected to thin layer and/or gas chromatography. The authors present also the relative frequency that they met on hexapropymate intoxications together with the concentrations in blood obtained in cases accompanied with deep coma.


Patients with radiographic axial spondylarthritis have an impaired dietary intake-a cross-sectional study with matched controls from northern Sweden.
Radiographic axial spondyloarthritis (r-axSpA) is one of the most common chronic inflammatory rheumatic diseases, affecting about 0.2% of the Swedish population. Adequate nutritional intake is essential for maintaining physiological functions. A poor diet increases the risk of developing conditions such as obesity, osteoporosis, and/or atherosclerosis. Diet quality is also theorized to affect systemic inflammation. Dietary habits in patients with r-axSpA are largely unknown. The aims of this study were to assess dietary nutrient intake in r-axSpA patients and examine whether it differs compared to persons without r-axSpA. r-axSpA patients (modified NY criteria) at the rheumatology clinic in Region Västerbotten, northern Sweden, were invited to take part in the Backbone study which investigates disease severity and comorbidities. In total, 155 patients were included. Nutritional intake was assessed by the semi-quantitative food frequency questionnaire MiniMeal-Q. Controls were collected from the Swedish CArdioPulmonary bioImage Study (n = 30,154), a study that invited participants 50-64 years of age by random selection from the Swedish population register. Out of the 155 r-axSpA patients, 81 were in the same age span. Four controls were identified for each patient, matched on age (± 1 year), sex, and geographic location. Data on dietary intake was available for 319 controls. Statistical comparisons of dietary intake between patients with r-axSpA and controls were done by exact conditional logistic regression analysis, adjusted for country of birth, educational level, single household, weight, smoking status, and energy intake. Patients had a comparatively significantly higher energy intake from carbohydrates, a lower fiber density, and a lower intake of marine omega-3 fatty acids. Furthermore, intake of vitamins D, E, and K as well as selenium, folate, calcium, magnesium, phosphorus, potassium, vitamin A, and β-carotene (a precursor of vitamin A and marker of vegetable and fruit intake) was significantly lower among patients compared to controls. Our results suggest that r-axSpA patients have an impaired dietary intake. Notably, intake was lower in several nutrients theorized to have anti-inflammatory properties (fiber density, marine-omega-3 fatty acids, vitamin D, and selenium). We further propose that nutrition screening might be incorporated into the management of r-axSpA patients.


[Ultrastructural changes in rabbit sensomotor cortex synapses following stimulation of the reticular formation].
Ultrastructural changes in the synapses of sensorimotor cortex caused by short and protracted stimulations of mid-brain reticular formation with single electric pulses were studied in rabbits. The observed submicroscopic shift in synaptic apparatus is regarded as a process of enhancing the activity of the sensorimotor synaptic apparatus with involvement of new interneuronal connections. Structural-functional changes in the synaptic apparatus occured at all levels of the sensorimotor cortex, with the predominance of this process at the upper level (layers I-IV); this is probably due to the greater representation of non-specific afferent endings in the upper cortical layers.


Field-based individual plant phenotyping of herbaceous species by unmanned aerial vehicle.
Recent advances in Unmanned Aerial Vehicle (UAVs) and image processing have made high-throughput field phenotyping possible at plot/canopy level in the mass grown experiment. Such techniques are now expected to be used for individual level phenotyping in the single grown experiment.We found two main challenges of phenotyping individual plants in the single grown experiment: plant segmentation from weedy backgrounds and the estimation of complex traits that are difficult to measure manually.In this study, we proposed a methodological framework for field-based individual plant phenotyping by UAV. Two contributions, which are weed elimination for individual plant segmentation, and complex traits (volume and outline) extraction, have been developed. The framework demonstrated its utility in the phenotyping of Helianthus tuberosus (Jerusalem artichoke), an herbaceous perennial plant species.The proposed framework can be applied to either small and large scale phenotyping experiments.


Expression of androgen receptors in benign and malignant endometrial stromal neoplasms.
Several studies have shown that endometrial stromal neoplasms express estrogen and progesterone receptors (ER, PR). To our knowledge, the presence or absence of androgen receptors (AR) in these rare uterine neoplasms has not been investigated. Tumors ( n=20)-3 endometrial stromal nodules, 14 low-grade endometrial stromal sarcomas (ESS, low grade), and 3 high-grade endometrial sarcomas (undifferentiated endometrial sarcoma, UES)-were studied. Immunohistochemical analyses for ER, PR, and AR were performed on formalin-fixed, paraffin-embedded archival material. Positive immunoreactions for ER and PR were observed in 14 (70%) and 17 (85%) cases, respectively. Furthermore, 9 cases (45%) were positive for AR. Among 17 ESS and UES cases, 7 (41%) revealed positivity for AR. Two of three benign stromal nodules were also positive for AR. Moreover, one of the three high-grade sarcomas (undifferentiated endometrial sarcoma) was negative for both ER and PR, but showed positive reaction for AR. In summary, ARs are expressed in 45% of endometrial stromal neoplasms. In addition to determination of ER and PR, the results of immunohistochemical examination of AR in these rare uterine tumors may have some impact on the postoperative management of the patients.


Educating a new generation of clinical laboratory scientists.
In many countries the new generation of laboratory scientists comes from the graduates of the biological sciences. Their training in the sciences is usually of high quality, but is almost totally lacking in the clinical application of their scientific knowledge. They obtain this clinical knowledge most often by on-the-job training and experience. This paper describes a new undergraduate academic program in Laboratory Medicine developed at the Faculty of Medicine of the Technion, the Israel Institute of Technology. The program is carried out with the collaboration of the Faculty of Biology and the Faculty of Medicine, and upon completion of the classroom studies there is a period of internship for practical experience. The first students of the program are now in their internship period and will graduate this year.


[Prevalence of osteoporosis in male patients with risk factors].
Male osteoporosis is often secondary to other conditions. However the causes of osteoporosis in men are dramatically variable according to the authors. The aim of this observational multicenter study was to assess the main risk factors and causes for male patients with low bone mineral density (LBM). The study was performed in a cohort of rheumatologists who usually prescribe bone mineral density assessment according to HAS criteria (one or more criteria) for bone mineral density (BMD) measurement as defined by: (a): vertebral fracture; (b): non traumatic non vertebral fracture; (c): corticosteroid therapy; (d): hypogonadism or GnRH agonist therapy; (e): endocrine disorders; (f): osteogenesis imperfecta (OI). BMD was measured by dual photon absorptiometry (DXA) at lumbar spine, femoral or total neck sites. Osteoporosis was defined as a T-score value less or equal to 2.5 at one of those region of interest (ROI); LBM as a T-score value between -1 and -2.5. A total of 431 rheumatologists included 1198 male patients (66.6 ± 12.2 years). According to DXA results, 888 patients (74.1 %) had osteoporosis and 231 (19.3 %) had osteopenia. BMD was considered as normal for 79 patients (6.6 %). A total of 1146 patients (95.7 %) satisfied to the criteria of reimbursement of DXA measurement. Six hundred and eighty-six patients (57.3 %) had suffered from vertebral fractures and 349 patients (29.2 %) from non vertebral fractures. Corticosteroids had been prescribed in 28.7 % of patients and 6.6 % were treated with GnRH agonists for prostate cancer. Hypogonadism was diagnosed in 27 %. Five patients suffered from OI. Other risk factors were detected: alcoholism and smoking in 28.1 % and 42.9 % respectively; rheumatoid arthritis or spondylarthropathy in 12.5 % of patients; chronic pulmonary disorders in 16.1 %. By contrast endocrinopathies were rare (2.5 %). Several risk factors were more frequently encountered for patients with osteoporosis as compared with osteopenia, i.e., smoking, alcohol abuse, low calcium intake, vitamin D insufficiency and maternal history of hip fracture. A diagnosis of osteoporosis (BMD ≤ 2.5) was established by rheumatologists in 74.1 % of patients with clinical risk factors: LBM was found in 93.4 %. In 95.7 % the criteria for reimbursement of DXA measurement were satisfied. DXA is useful in male patients with classical risk factors of osteoporosis to confirm the diagnosis of the disease and start a treatment.


Quality changes of salmon by-products during storage: Assessment and quantification by NMR.
Safe utilization of fish by-products is an important task due to increasing fish consumption. It can provide new valuable food/feed and will increase the economical profit and sustainability of the fishery industry. NMR spectroscopy is a reliable tool able to monitor qualitative and quantitative changes in by-products. In this work the trichloroacetic acid extracts of salmon backbones, heads and viscera stored at industrially relevant temperatures (4 and 10°C) were studied using NMR. Twenty-five metabolites were detected and the possibility of salmon by-products utilization as a source of anserine, phosphocreatine and taurine was discussed. Statistical data elaboration allowed determining the main processes occurring during by-products storage: formation of trimethylamine and biogenic amines, proteolysis and different types of fermentations. By-products freshness was evaluated using a multi-parameter approach: the trimethylamine and biogenic amines concentration changes were compared with Ki and H-values and safe temperatures and times for storage of salmon by-products were proposed.


Silicone-associated tissue reaction: a dilemma for oral and maxillofacial surgeons.
A case report of cystic encapsulation of a silicone elastomer (Silastic: Polydimethyl Siloxane, Dow Corning Ltd) orbital floor implant is described. This is a known, but poorly understood complication of implanted silicone elastomer. Comparison is made with other complications associated with Silastic, and attention drawn to the phenomenon of excessive collagen formation demonstrated by the thick collagen cyst lining, analogous to fibrous 'cricket ball' breast implant encapsulation, which may be peculiar to certain predisposed individuals.


Avascular necrosis of the femoral head in patients receiving intermittent cytotoxic and corticosteroid therapy for Hodgkin's disease.
Two patients with stage IIIB Hodgkin's disease are reported, in whom treatment with cytotoxic and corticosteroid therapy was followed by avascular necrosis of the femoral head.


Estimating micro area behavioural risk factor prevalence from large population-based surveys: a full Bayesian approach.
An important public health goal is to decrease the prevalence of key behavioural risk factors, such as tobacco use and obesity. Survey information is often available at the regional level, but heterogeneity within large geographic regions cannot be assessed. Advanced spatial analysis techniques are demonstrated to produce sensible micro area estimates of behavioural risk factors that enable identification of areas with high prevalence. A spatial Bayesian hierarchical model was used to estimate the micro area prevalence of current smoking and excess bodyweight for the Erie-St. Clair region in southwestern Ontario. Estimates were mapped for male and female respondents of five cycles of the Canadian Community Health Survey (CCHS). The micro areas were 2006 Census Dissemination Areas, with an average population of 400-700 people. Two individual-level models were specified: one controlled for survey cycle and age group (model 1), and one controlled for survey cycle, age group and micro area median household income (model 2). Post-stratification was used to derive micro area behavioural risk factor estimates weighted to the population structure. SaTScan analyses were conducted on the granular, postal-code level CCHS data to corroborate findings of elevated prevalence. Current smoking was elevated in two urban areas for both sexes (Sarnia and Windsor), and an additional small community (Chatham) for males only. Areas of excess bodyweight were prevalent in an urban core (Windsor) among males, but not females. Precision of the posterior post-stratified current smoking estimates was improved in model 2, as indicated by narrower credible intervals and a lower coefficient of variation. For excess bodyweight, both models had similar precision. Aggregation of the micro area estimates to CCHS design-based estimates validated the findings. This is among the first studies to apply a full Bayesian model to complex sample survey data to identify micro areas with variation in risk factor prevalence, accounting for spatial correlation and other covariates. Application of micro area analysis techniques helps define areas for public health planning, and may be informative to surveillance and research modeling of relevant chronic disease outcomes.


Corneal edema associated with degenerating Soemmering ring cataract: Clinical-pathologic correlation.
To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract. We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified Soemmering ring cataract. Histopathological examination demonstrated extracellular calcific deposits compatible with cataractous lens material on the posterior surface of stripped Descemet membrane of two patients. The deposits were associated with prominent localized loss of corneal endothelium and were not associated with inflammation. Morphologically similar acellular material was identified in the biopsied aqueous and vitreous fluid of one patient. Management included endothelial keratoplasty, anterior chamber lavage, pars plana vitrectomy, aspiration/removal of a portion of Soemmering ring cataract without intraocular lens implant explantation, and the removal of the entire capsular bag/implant complex. Cornea cleared and visual acuity improved in both patients who underwent endothelial keratoplasty. Persistent elevated intraocular pressure led to visual deterioration in one patient with secondary glaucoma. Dispersion of calcific Soemmering ring cataract can occur decades following cataract surgery leading to corneal edema, secondary glaucoma, and vitreous opacities. Timely recognition of this phenomenon may prevent ocular morbidity, including corneal edema and glaucoma.


Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.
We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each. In Arm A, 90% of vaccinated girls/boys, and in Arm B, 90% of vaccinated girls received AS04-HPV-16/18 vaccine. Other Arm A/B and all Arm C vaccinated participants received control vaccine. All Arm A participants and Arm B female participants were blinded to vaccine allocation. Oropharyngeal samples were analyzed from 4,871 18.5-year-old females who attended follow-up visit 3-6 years postvaccination. HPV DNA prevalence was determined by SPF-10 LiPA and Multiplex type-specific PCR. Total vaccine effectiveness (VE) was defined as relative reduction of oropharyngeal HPV prevalence in pooled Arms A/B HPV-vaccinated females vs. all Arm C females. VE against oropharyngeal HPV-16/18, HPV-31/45 and HPV-31/33/45 infections were 82.4% (95% confidence intervals [CI]: 47.3-94.1), 75.3% (95%CI: 12.7-93.0) and 69.9% (95% CI: 29.6-87.1), respectively. In conclusion, the AS04-HPV-16/18 vaccine showed effectiveness against vaccine and nonvaccine HPV-types oropharyngeal infections in adolescent females up to 6 years postvaccination.


Chemoenzymatic Total Synthesis and Structural Revision of Ampelomins B, D, E, and epi-Ampelomin B.
Enantioselective synthesis of ampelomin B and epi-ampelomin B, D, and E was accomplished starting from toluene, through a chemoenzymatic sequence, in which stereoselective hydrogenation, Mitsunobu reaction, and regio- and stereoselective nucleophilic opening of an epoxide were used as the main transformations. Structural revision and absolute configuration of the natural compounds were carried out.


Composition and source apportionment of surfactants in atmospheric aerosols of urban and semi-urban areas in Malaysia.
This study was conducted to determine the composition and source apportionment of surfactant in atmospheric aerosols around urban and semi-urban areas in Malaysia based on ionic compositions. Colorimetric analysis was undertaken to determine the concentrations of anionic surfactants as Methylene Blue Active Substances (MBAS) and cationic surfactants as Disulphine Blue Active Substances (DBAS) using a UV spectrophotometer. Ionic compositions were determined using ion chromatography for cations (Na(+), NH4(+), K(+), Mg(2+), Ca(2+)) and anions (F(-), Cl(-), NO3(-), SO4(2-)). Principle component analysis (PCA) combined with multiple linear regression (MLR) were used to identify the source apportionment of MBAS and DBAS. Results indicated that the concentrations of surfactants at both sampling sites were dominated by MBAS rather than DBAS especially in fine mode aerosols during the southwest monsoon. Three main sources of surfactants were identified from PCA-MLR analysis for MBAS in fine mode samples particularly in Kuala Lumpur, dominated by motor vehicles, followed by soil/road dust and sea spray. Besides, for MBAS in coarse mode, biomass burning/sea spray were the dominant source followed by motor vehicles/road dust and building material.


Electrical resistance of the cochlear partition.
The relationship between the calculated value of the effective electrical resistance of the cochlear partition and the distance between the electrode for measuring the EP and the stimulating electrodes has been studied. The calculated value of the effective electrical resistance of the cochlear partition declines linearly with increasing distance between these electrodes. The correlation coefficient (r) is -0.806. In calculations of the effective electrical resistance of the cochlear partition, attention must be paid to the distance between the microelectrodes.


An isoflavone cladrin prevents high-fat diet-induced bone loss and inhibits the expression of adipogenic gene regulators in 3T3-L1 adipocyte.
This study evaluates the effect of isoflavone cladrin on high-fat diet (HFD)-induced bone loss and adipogenesis. Thirty-two 4-week-old male C57BL/6J mice were divided into four groups: a standard diet group, a HFD group and HFD group with cladrin (5 and 10 mg/kg per day orally) for 12 weeks. The effect of cladrin on bone micro-architecture, bone marrow cell lineages and hyperlipidaemia were assessed. For assessing anti-adipogenic activity of cladrin, 3T3-L1 cells were used. Cladrin attenuated HFD-induced hyperlipidaemia and bone loss by preserving bone micro-architecture and strength. Effect of cladrin was found at the level of bone marrow progenitor cells. Gene expression profile of cladrin-treated mice bone showed upregulation of osteoblast and downregulation of adipogenic transcription factors and increased OPG/RANKL ratio. Cladrin inhibited cellular lipid accumulation through downregulation of transcription factors such as PPAR-γ and C/EBP-α and modulated the expression of major adipokines involved behind obesity stimulation without eliciting cell cytotoxicity in 3T3-L1 adipocytes. We conclude that cladrin may improve obesity-induced bone loss and hyperlipidaemia in mice fed HFD and adipogenesis in 3T3-L1 cells by modifying adipokines and could offer clinical benefits as a supplement to treat obesity-induced disorders.


Threshold control of arm posture and movement adaptation to load.
We addressed the fundamental questions of which variables underlie the control of arm movement and how they are stored in motor memory, reproduced and modified in the process of adaptation to changing load conditions. Such variables are defined differently in two major theories of motor control (internal models and threshold control). To resolve the controversy, these theories were tested (experiment 1) based on their ability to explain why active movement away from a stable posture is not opposed by stabilizing mechanisms (the posture-movement problem). The internal model theory suggests that the system counteracts the opposing forces by increasing the muscle activity in proportion to the distance from the initial posture (position-dependent EMG control). In contrast, threshold control fully excludes these opposing forces by shifting muscle activation thresholds and thus resetting the stabilizing mechanisms to a new posture. Subjects were sitting, holding the vertical handle of a double-joint manipulandum with their right hand and were facing a computer screen on which the handle and target to be reached were displayed. In response to an auditory signal, subjects quickly moved the handle from an initial position to one of two (frontal and sagittal) targets. No load was applied during the movement but in separate trials, a brief perturbation was applied to the handle by torque motors controlling the manipulandum. Perturbations were applied prior to or 3 s after movement offset, in the latter case in one of eight directions. The EMG activity of the majority of the seven recorded muscles was at zero level before movement onset and returned to zero level after movement offset. Those muscles that remained active before or after the movement could be made silent whereas previously silent muscles could be activated after a small passive displacement (several millimeters) elicited by perturbations in appropriate directions. Results showed that the activation thresholds of motoneurons of arm muscles were reset from the initial to a final position and that EMG activity was not position-dependent. These results were inconsistent with the internal model theory but confirmed the threshold control theory. Then the ability of threshold control theory to explain rapid movement adaptation to a position-dependent load was investigated (experiment 2 and 3). Subjects produced fast movement to the frontal target with and without a position-dependent load applied to the handle. Trials were organized in blocks alternating between the load and no-load condition (20 blocks in total, with randomly chosen number of five to ten trials in each). Subjects were instructed "do not correct" in experiment 2 and "correct" movement errors during the trial in experiment 3. Five threshold arm configurations underlying the movement production and adaptation were identified. When instructed "do not correct", movement precision was fully restored on average after two trials. No significant improvement was observed as the experiment progressed despite the fact that the same load condition was repeated after one block of trials. Thus, in each block, the adaptation was made anew, implying that subjects relied on short-term memory and could not recall the threshold arm configurations they specified to accurately reach the same target in the same load condition in previous blocks. When instructed to "correct" within each trial, precision was restored faster, on average after one trial. Major aspects of the production and adaptation of arm movement (including the kinematics, movement errors, instruction-dependent behavior, and absence of position-related EMG activity) are explained in terms of threshold control.


Occupational health patients' parallel use of primary- and secondary-care services and linkage to work disability: A follow-up study in Finland.
This study aimed to investigate occupational health (OH) primary-care patients' use of other health-care services and whether parallel use affects their likelihood to have sickness absences (SA) or disability pensions (DP). Primary-care services in Finland are provided through three parallel health-care sectors, all available to the working population: public, private and OH sectors. Patients may also be referred to secondary care. This follow-up study combines real-world medical record data containing SA data from a nationwide OH provider with health-care attendance data from public and private primary-care sectors and public secondary care, sociodemographic data and DP decisions. Patients between 18 and 68 years of age who used OH primary care at least once during the study years 2014-2016 were included. The total study population comprised 59,650 patients. Odds ratios were used to analyse association between parallel service use and SA or DP. Females and patients with a lower educational level were more likely to use services in other health-care sectors in addition to OH than others. Those patients who used any other health-care sector in addition to OH primary care had an increased likelihood of having long SA or receiving DP. OH primary-care patients using the services of several health-care sectors in parallel have an increased likelihood of receiving disability benefits - either SA or DP. There is need for care coordination to ensure adequate measures for work-ability support.


Down-regulation of human FEN-1 gene expression during differentiation of promyelocytic leukemia cells.
Flap endo/exonuclease-1 (FEN-1) recognizes 5'-flap DNA structures that have been proposed to be important intermediates in DNA replication, repair and recombination, and cleaves the double strand-single strand junction of flap substrates. Using an in vitro model system, recent studies have shown that FEN-1 is a necessary enzyme for the removal of RNA primers in Okazaki fragment maturation during lagging strand DNA synthesis. In this report, the FEN-1 gene expression was examined during cell cycle and differentiation. Although FEN-1 mRNA and protein could be detected at all stages of the cell cycle, their levels were more elevated in exponentially proliferating cells than in G1 or G2/M-synchronized cells. Moreover, a significant increase of FEN-1 protein was observed when temporarily quiescent fibroblasts were induced to proliferate by serum stimulation. In contrast, the FEN-1 mRNA level showed a sharp decrease in HL-60 cells differentiated by dimethyl-sulfoxide, all-trans retinoic acid or 12-O-tetradecanoylphorbol-13-acetate. These results demonstrate that the FEN-1 gene expression is up-regulated during entrance into the mitotic cell cycle and down-regulated in nongrowing cells, as in the case of differentiated promyelocytic leukemia cells.


A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases.
The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.


A Sentinel-2 derived dataset of forest disturbances occurred in Italy between 2017 and 2020.
Forests absorb 30% of human emissions associated with fossil fuel burning. For this reason, forest disturbances monitoring is needed for assessing greenhouse gas balance. However, in several countries, the information regarding the spatio-temporal distribution of forest disturbances is missing. Remote sensing data and the new Sentinel-2 satellite missions, in particular, represent a game-changer in this topic. Here we provide a spatially explicit dataset (10-meters resolution) of Italian forest disturbances and magnitude from 2017 to 2020 constructed using Sentinel-2 level-1C imagery and exploiting the Google Earth Engine GEE implementation of the 3I3D algorithm. For each year between 2017 and 2020, we provide three datasets: (i) a magnitude of the change map (between 0 and 255), (ii) a categorical map of forest disturbances, and (iii) a categorical map obtained by stratification of the previous maps that can be used to estimate the areas of several different forest disturbances. The data we provide represent the state-of-the-art for Mediterranean ecosystems in terms of omission and commission errors, they support greenhouse gas balance, forest sustainability assessment, and decision-makers forest managing, they help forest companies to monitor forest harvestings activity over space and time, and, supported by reference data, can be used to obtain the national estimates of forest harvestings and disturbances that Italy is called upon to provide.


[Is there still a role for radical cystectomy in localized, infiltrating bladder cancers in 1998?].
The role of radical cystectomy as the standard treatment of localised infiltrating bladder malignancy is challenged by the development radiotherapy and chemotherapy combinations. The published studies are difficult to compare because of large differences in the patients selection criteria and in the assessment of local involvement (only clinical in combined treatment, based on pathology and therefore unquestionable in surgical series). The advantages of radical surgery are its precedence and a well-established technique, simplified follow-up procedures and seemingly higher survival rates acquired after 3 years. Conversely, the combination of radiotherapy and chemotherapy allows bladder preservation in about 40% of the patients (at 5 years), but only in 23% without bladder relapses. A complete initial endoscopic resection is the best and only prognostic factor of these results which nevertheless needs a very carefully and endless follows. The comparison of the quality of life achieved by both treatment modalities remains insufficiently documented.


Angelman syndrome and prenatally diagnosed Prader-Willi syndrome in first cousins.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of function of imprinted genes in the 15q11-13 critical region. Reports of PWS and AS in close relatives within the same family are rare. We report on the diagnosis of a familial unbalanced 10;15 translocation causing AS in a child that led to the prenatal diagnosis of an unbalanced 10;15 translocation with resultant deletion of the Prader-Willi critical region in her maternal uncle's offspring.


Diagnosis of Alzheimer's disease and related dementia among people with multiple sclerosis: Large cohort study, USA.
Alzheimer's disease and related dementia (ADRD) and multiple sclerosis (MS) are two neurodegenerative diseases with some shared pathophysiological characteristics. While the salient attribute of ADRD is a progressive decline in cognitive function, MS is mainly known for causing physical weakness, vision loss, and muscle stiffness. Progressive cognitive decline, however, is not uncommon among MS patients, and many case reports of MS were indicative of ADRD coexistence. Due to a lack of large epidemiological studies on this topic, we aimed to examine time to diagnosis of and adjusted hazard for ADRD using administrative claims data, comparing adults with and without MS. Using 2007-2017 private claims data from Optum Clinformatics Data Mart in the U.S., we identified adults (45+) with a MS diagnosis (n = 6151) as well as adults without MS for comparison (n = 916,143). We propensity score matched people with MS with those without (n = 6025) using age, sex, race/ethnicity, chronic conditions including cardiometabolic, psychologic, and musculoskeletal, U.S. Census Division, and socioeconomic variables. In addition to incidence estimates of ADRD diagnosis compared at 4-years, survival models were utilized to quantify unadjusted, fully adjusted, and adjusted propensity-matched hazard ratios. Unmatched data revealed that incidence of early-onset ADRD diagnosis was 7 times higher among adults 45-64 years old with MS (1.4%) compared to those without (0.2%); among older adults (65+) with MS, incident ADRD was 4.0% compared to 3.3% among those without MS. Adjusted survival models indicated that adults with MS had a substantially high risk for early-onset ADRD diagnosis (among 45-64 years old: unmatched hazard ratio (HR): 4.25 (95% CI: 3.40 -5.32), matched HR: 4.49 (95% CI:2.62-7.69); among 65+ years old: unmatched HR: 1.39 (95% CI: 1.22, 1.58), matched HR: 1.26 (1.04, 1.54)). Individuals with MS had a greater incidence of and risk for early- and late-onset ADRD diagnosis compared to those without MS. It is not clear whether this greater risk is due to an accelerated dementia risk or at least partially due to clinical misdiagnosis. Advancements in the development of clinical and imaging biomarkers should be more commonly used in clinical settings to facilitate future research on this topic.


Type III home sleep testing versus pulse oximetry: is the respiratory disturbance index better than the oxygen desaturation index to predict the apnoea-hypopnoea index measured during laboratory polysomnography?
In its guidelines on the use of portable monitors to diagnose obstructive sleep apnoea, the American Academy of Sleep Medicine endorses home polygraphy with type III devices recording at a minimum airflow the respiratory effort and pulse oximetry, but advises against simple pulse oximetry. However, oximetry is widely available and simple to use in the home. This study was designed to compare the ability of the oxygen desaturation index (ODI) based on oximetry alone with a stand-alone pulse oximeter (SPO) and from the oximetry channel of the ApneaLink Plus (ALP), with the respiratory disturbance index (RDI) based on four channels from the ALP to predict the apnoea-hypopnoea index (AHI) from laboratory polysomnography. Cross-sectional diagnostic accuracy study. Sleep medicine practice of a multispecialty clinic. Patients referred for laboratory polysomnography with suspected sleep apnoea. We enrolled 135 participants with 123 attempting the home sleep testing and 73 having at least 4 hours of satisfactory data from SPO and ALP. Participants had home testing performed simultaneously with both a SPO and an ALP. The 2 oximeter probes were worn on different fingers of the same hand. The ODI for the SPO was calculated using Profox software (ODI(SOX)). For the ALP, RDI and ODI were calculated using both technician scoring (RDI(MAN) and ODI(MAN)) and the ALP computer scoring (RDI(RAW) and ODI(RAW)). The receiver-operator characteristic areas under the curve for AHI ≥ 5 were RDI(MAN) 0.88 (95% confidence limits 0.81-0.96), RDI(RAW) 0.86 (0.76-0.94), ODI(MAN) 0.86 (0.77-0.95), ODI(RAW) 0.84 (0.75-0.93) and ODI(SOX) 0.83 (0.73-0.93). We conclude that the RDI and the ODI, measured at home on the same night, give similar predictions of the laboratory AHI, measured on a different night. The differences between the two methods are small compared with the reported night-to-night variation of the AHI.


Physiotherapy in Parkinson's Disease: A Meta-Analysis of Present Treatment Modalities.
Physiotherapy is a commonly prescribed intervention for people with Parkinson's disease (PD). Conventional types of physiotherapy have been studied extensively, while novel modalities are being developed and evaluated. To evaluate the effectiveness of conventional and more recent physiotherapy interventions for people with PD. The meta-analysis performed as part of the 2014 European Physiotherapy Guideline for PD was used as the starting point and updated with the latest evidence. We performed a systematic search in PubMed, CINAHL, Embase, and Web of Science. Randomized controlled trials comparing any physiotherapy intervention with no intervention or sham treatment were included. Trials were classified into 12 categories: conventional physiotherapy, resistance training, treadmill training, strategy training, dance, martial arts, aerobic exercises, hydrotherapy, balance and gait training, dual tasking, exergaming, and Nordic walking. Outcomes included motor symptoms, balance, gait, and quality of life, and are presented as standardized mean differences. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to systematically appraise methodological quality. A total of 191 trials with 7998 participants were included. Conventional physiotherapy significantly improved motor symptoms, gait, and quality of life. Resistance training improved gait. Treadmill training improved gait. Strategy training improved balance and gait. Dance, Nordic walking, balance and gait training, and martial arts improved motor symptoms, balance, and gait. Exergaming improved balance and quality of life. Hydrotherapy improved balance. Finally, dual task training did not significantly improve any of the outcomes studied. This meta-analysis provides a comprehensive overview of the evidence for the effectiveness of different physiotherapy interventions in the management of PD, allowing clinicians and patients to make an evidence-based decision for specific treatment modalities. Further work is needed to directly compare the relative efficacy of the various treatments.


MRI-based estimation of liver function by intravoxel incoherent motion diffusion-weighted imaging.
To explore the usefulness of intravoxel incoherent motion (IVIM) to evaluate the hepatic functional reserve as expressed by the model for Child-Pugh class. IVIM diffusion-weighted imaging (DWI) using 10 different b values were performed on a Philips 3.0T MR scanner in 70 patients with liver cirrhosis and 60 healthy volunteers as the control group. Patients with liver cirrhosis were subdivided into three groups: Child-Pugh class A: 29 cases; Child-Pugh class B: 19 cases; Child-Pugh class C: 22 cases. Pure molecular diffusion (D), pseudo-diffusion (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated, and used to determine liver function, as indicated by the Child-Pugh class. The ICC values of D, D*, f and ADC between two radiologists were 0.997, 0.986, 0.985 and 0.995, respectively. D*, f and ADC values of liver cirrhosis group were significantly lower than control group (P<0.001, P=0.016, P=0.042, respectively). D*, f and ADC values significantly decreased with increasing Child-Pugh scores (p<0.05). Child-Pugh scores were inversely correlated with D* and f values (r=-0.423, r=-0.620, respectively). The areas under the curve (AUCs) of D* and f for evaluating liver function were 0.67-0.90 and 0.78-0.89, respectively. IVIM DWI may be a useful image-based method for assessing liver function.


Palmar Shift of the Proximal Interphalangeal Joint in Different Grip Positions as a Potential Risk Factor for Periphyseal Injuries in Adolescent Climbers.
The aim of this study was to evaluate different grip positions as a contributing factor for primary periphyseal stress injuries of the finger phalanges in climbing. Ultrasound imaging of the proximal interphalangeal joint was performed on 37 asymptomatic adolescent climbers. Longitudinal images were obtained of middle and ring fingers of both hands in different grip positions (open, half-open, and crimp), unloaded and loaded. The translation between the dorsal head of the proximal phalanx and the shaft of the middle phalanx was measured in an unloaded and loaded situation for all grip positions. The resulting difference was determined as the palmar shift. The mean age of the study population was 13 y. Results showed a palmar shift of 0.57 mm in a loaded crimp grip position compared to 0.13 mm in an open position and 0.20 mm in a half-open grip position. With a P value of <0.001, this shift was significantly higher in a crimp grip position compared to open or half-open grip positions. This leads to an increase in joint incongruity and much higher peak forces on the dorsal aspect of the epiphyseal-physeal-metaphyseal complex, which is particularly vulnerable during the adolescent growth spurt. Thus, climbing and training behavior should be adapted accordingly during this phase by avoiding the crimp grip position until epiphyseal fusion.


Developing an Evidence-Based Epilepsy Risk Assessment eHealth Solution: From Concept to Market.
Sudden unexpected death in epilepsy (SUDEP) is possibly the most common cause of death as a result of complications from epilepsy. The need to educate and regularly review risk for all patients with epilepsy is paramount, but rarely delivered in actual clinical practice. Evidence suggests that education around SUDEP and modifiable risk variables translate into better self-management of epilepsy. We aimed to develop and implement an eHealth solution to support education and self-management of risks, in epilepsy. We undertook an innovation pathways approach, including problem identification, feasibility assessment, design, implementation, and marketing. People with epilepsy were provided a smartphone-based app (Epilepsy Self-Monitor, EpSMon), which translates the clinical risk assessment tool into an educational and self-monitoring platform, for the self-management of epilepsy. Results include the success of the marketing campaign, and in what areas, with an estimated reach of approximately 38 million people. EpSMon has proved a success in academic and clinical circles, attracting awards and nominations for awards. The number of users of EpSMon, after 3 months, turned out to be lower than expected (N=221). A 4-month trial of the app in use in the United Kingdom, and the success of the marketing strategy, point to necessary changes to the model of delivery and marketing, summarized in this paper. These include the marketing message, user cost model, and need for the availability of an Android version. EpSMon has proven a success in respect to its reception by academics, clinicians, stakeholder groups, and the patients who use it. There is work needed to promote the model and increase its acceptability/attractiveness, including broadening the marketing message, increasing its availability, and reducing its cost. Future development and promotion of the tool will hopefully inform iterative design of its core features for a receptive audience and lead to increased uptake as it is launched worldwide in 2016.


Suction blister device with regulation of temperature: demonstration of histamine release and temperature change in cold urticaria.
A suction blister device with a sensitive thermometer and with a temperature regulator was constructed. Utilizing this device, it was demonstrated that the cold challenge induces an increase in the skin temperature in cold urticaria patients during the cold challenge and a simultaneous release of histamine into the suction blisters. The skin temperature increases faster after the cold challenge period in cold urticaria patients than in normal control persons. This could be explained by vasodilatation and increased circulation in the skin, following the release of histamine in the cold urticaria reaction.


Imaging and detection of sulfite in acute liver injury with a novel quinoxaline-based fluorescent probe.
Herein, a novel fluorescent probe HZY was developed for monitoring the sulfite (SO32-) dynamics. For the first time, the SO32- triggered implement was applied in the acute liver injury (ALI) model. The levulinate was selected to achieve the specific and relatively steady recognition reaction. With the addition of SO32-, the fluorescence response of HZY exhibited a large Stokes shift of 110 nm under the 380 nm excitation. The merits included high selectivity under various pH conditions. Compared with the reported fluorescent probes for sulfite, HZY indicated above-moderate performances including remarkable and rapid response (40 folds, within 15 min), and high sensitivity (limit of detection = 0.21 μM). Further, HZY could visualize the exogenous and endogenous SO32- level in living cells. Moreover, HZY could gauge the changing levels of SO32- in three types (induced by CCl4, APAP, and alcohol) of ALI models. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that HZY could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic of SO32-. The successful implementation of this project would promote the accurate in-situ detection of SO32- in liver injury, which was expected to guide the pre-clinical diagnosis and clinical practice.


The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.
Like the systemic inflammatory response syndrome (SIRS), the compensatory anti-inflammatory response syndrome (CARS) is a complex pattern of immunologic responses to severe infection or injury. The difference is that while SIRS is a proinflammatory response tasked with killing infectious organisms through activation of the immune system, CARS is a global deactivation of the immune system tasked with restoring homeostasis. Much research now suggests that the timing and relative magnitude of this response have a profound impact on patient outcomes.


Effect of equilibrium pH on the structure and properties of bleach-damaged human hair fibers.
Hair proteins are significantly affected by environmental pH. This impact tends to increase with prior hair damage. To understand how pH affects bleached hair properties, we utilized a number of techniques allowing for the determination of hair thermal properties, swelling and water sorption, and dry and wet tensile properties. At pH 5, hair proteins had the best structural integrity, as determined by differential scanning calorimetry and the highest tensile modulus. At pH 10, protein cross-linking density decreased, water content and hair cross-sectional diameter increased. Alkaline treatment, when compared with pH 5, did not reduce intermediate filament conditions (evaluated via enthalpy measurement) nor mechanical property performance in the wet state. In contrast to alkaline-treated hair, bleached hair equilibrated at pH 3 behaved very differently: it contained two different crosslink density zones, was the least stiff in dry and stiffest in wet conditions. Additionally, it absorbed less water and had the lowest diameter because of reduced water binding by protonated carboxyl groups. The pH 3 to 10 did not affect the mechanical strength of bleached hair in dry or wet conditions.


Fidelity of histone synthesis in cultured human fibroblasts.
The results in the literature to support Orgel's general error hypothesis of ageing only provide indirect evidence that errors in protein synthesis increase during senescence. This study attempts to provide direct evidence of errors in protein synthesis by measuring the misincorporation of 35S-methionine into histone H1 obtained from young and old fibroblasts (MRC-5). The conclusions that can be drawn from this study are: (a) the error level for the misincorporation of methionine into histone H1 is less than 7 methionines/10(5) amino acids and 2-3 methionines/10(4) amino acids in young and old cells respectively; (b) a methionine containing fraction associated with H1 is obtained after the final purification. The amount of this fraction increases with the age of the cell culture as does the number of methionine residues; (c) there is a variation in the complexity of H1 polypeptide chains, the complexity increasing with the age of cultured cells.


Randomized study comparing the efficacy of a self-retaining bicanaliculus intubation stent with Crawford intubation in patients with canalicular obstruction.
The purpose of this study was to compare the efficacy of self-retaining stent (SRS) bicanalicular intubation with bicanalicular silicone (Crawford) intubation in patients with canalicular and punctal obstruction. In this prospective, randomized clinical trial, 38 patients with canalicular or punctal obstruction (25 partial, 13 complete) and epiphora were randomized into two groups. Twenty-one patients (14 with partial and seven with complete obstruction) underwent SRS intubation and 17 patients underwent bicanalicular silicon intubation in a randomized fashion. After a mean follow-up of 6 months following tube removal, 16 (76%, 12 partial, four complete) of the 21 eyes in the SRS intubation group and 13 (76%, 10 partial, three complete) in the bicanalicular silicon intubation group had a successful outcome and remained symptom-free. For partial obstructions, the success rate was 85% and 90% for the SRS and bicanalicular silicon intubation groups, respectively. The corresponding values for complete obstruction were 63% and 50% for the SRS and bicanalicular silicon intubation groups, respectively. SRS could effectively substitute for a more extensive procedure such as bicanalicular silicon intubation in patients with canalicular obstruction, particularly those with partial obstruction. The newly developed SRS intubation procedure has the advantages of simple, easy implementation and extubation, low cost, and a lower rate of trauma when compared with bicanalicular silicon intubation.


The in vitro inhibition of bovine milk lipoprotein lipase by a glycoprotein preparation from human atherosclerotic intima.
Intimal tissue from human atherosclerotic aortae was collected by the Dermatome procedure. The tissue was extraved with 5 mM Tris.HCl buffer containing 0.3 M NaCl and 1 mM EDTA, pH 7.4. The ammonium sulfate precipitate between 0.4--0.8 saturation obtained from the extract was fractionated on a DEAE-cellulose column and the effluent was monitored for lipoprotein lipase inhibition employing purified bovine milk enzyme. The substrate used was an emulsion of purified olive oil and tritiated triolein. Human serum was the source of activator of the substrate. A peak of inhibitory activity was eluted between 0.15--0.17 M NaCl. The major component in the purified material had properties similar to a glycoprotein (lipolipin) which has previously been purified from porcine aorta and shown to inhibit lipoprotein lipase activity. The partially purified human inhibitor decreased both the basal and the serum-stimulated activity of milk lipoprotein lipase. The inhibition was non-competitive with respect to serum. However, high levels of triglyceride substrate appeared to relieve the inhibitory effect. It is postulated that the inhibitor may be involved in an interaction with the emulsified lipid denying the enzyme access to its substrate.


Analyzing Outcomes Among Older Adults With Necrotizing Soft-Tissue Infections in the United States.
Necrotizing soft-tissue infections (NSTIs) encompass a group of severe, life-threatening diseases with high morbidity and mortality. Evidence suggests advanced age is associated with worse outcomes. To date, no large data sets exist describing outcomes in older individuals, and risk factor identification is lacking. Retrospective data were obtained from the 2015 Medicare 100% sample. Included in the analysis were those aged ≥65 y with a primary diagnosis of an NSTI (gas gangrene, necrotizing fasciitis, cutaneous gangrene, or Fournier's gangrene). Risk factors for in-hospital mortality and discharge disposition were examined. Continuous variables were assessed using central tendency, t-tests, and Wilcoxon rank-sum tests. Categorical variables were assessed using the chi-squared and Fisher's exact tests. Statistical significance was defined as P < 0.05. 1427 patient records were reviewed. 59% of patients were male, and the overall mean age was 75.4±8.6 y. 1385 (97.0%) patients required emergency surgery for their NSTI diagnosis. The overall mortality was 5.3%. Several underlying comorbidities were associated with higher rates of mortality including cancer (OR: 3.50, P = 0.0009), liver disease (OR: 2.97, P = 0.03), and kidney disease (OR: 2.15, P = 0.01). While associated with high in-hospital mortality, these diagnoses were not associated with a difference in the rate of discharge to home compared with skilled nursing or rehab. Overall, patients discharged to skilled nursing facilities or rehab had higher rates of underlying comorbidities than patients who were discharged home (3 or more comorbid illness 84.3% versus 68.6%, P < 0.0001); however, no individual comorbid illness was associated with discharge location. In our Medicare data set, we identified several medical comorbidities that are associated with increased rates of in-hospital mortality. Patients with underlying cancers had the highest odds of increased mortality. The effect on outcomes of the potentially immunosuppressive cancer treatments in these patients is unknown. These data suggest that patients with underlying illnesses, especially cancer, kidney disease, or liver disease have higher mortalities and are more likely to be discharged to skilled nursing facilities or rehab. It is unclear why these illnesses were associated with these worse outcomes while others including diabetes and heart disease were not. These data suggest that these particular comorbid illnesses may have special prognostic implications, although further analysis is necessary to identify the causative factors.


Tumor expression studies indicate that HEM-1 is unlikely to be the active factor in oncogenic osteomalacia.
HEM-1 was isolated as a putative factor responsible for oncogenic osteomalacia by Kumar et al. (Proc Assoc Am Phys 107:296-305; 1995). The cDNA was identified on the basis of PTH-like immunoreactivity; however, no studies have been reported of the expression of HEM-1 mRNA in oncogenic osteomalacia tumors. In this study, expression of HEM-1 mRNA was investigated in two oncogenic osteomalacia tumors and in a series of normal tissues. An HEM-1 PCR product was amplified from a cDNA library from one of the tumors, with six base changes identified, as compared with the published sequence. No expression was detected, however, in the oncogenic osteomalacia tumors either by Northern blot analysis or by reverse transcriptase PCR. This indicates that, although a region of HEM-1 sequence is present in the tumor cell cDNA library, any HEM-1 expression must be at very low levels. It is unlikely, therefore, that the HEM-1 product is the active factor responsible for oncogenic osteomalacia. In the normal tissues examined, human placenta, fibroblasts, parathyroid gland, liver, fetal bone, and rat kidney cortex, HEM-1 mRNA was not detected, suggesting that it does not have a physiological role in these tissues.


The clinical use of a fast screening test based on technology of capillary zone electrophoresis (CZE) for identification of Escherichia coli infection in biological material.
Escherichia coli is a Gram-negative bacterium which is a basic, symbiotic element of the physiological flora of the large intestine of humans and warm-blooded animals. However, in specific cases it may become a very dangerous pathogen (eg, diarrhoea, infection of the urinary tract, lungs, and generalized infections). Its early detection, as a cause of infectious disease, helps to achieve optimal treatment results; however, classical microbiological tests require at least 24 hours from sample taking to diagnosis. We present a unique solution based on CZE technologies enabling identification of E. coli presence in studied sample within half an hour. Altogether, 30 E. coli-infected wounds and ulcerations were examined, comparing the results obtained by classical culture method with the result of capillary zone electrophoresis (CZE) electropherogram. The method, which does not require any preparation of the sample, achieved 86.7% sensitivity and 85%specificity in the examined clinical material (infections of surgical wounds). The obtained results enable reliable, very fast testing for E. coli as a pathogen.


Distribution of crushing strength of tablets.
The distribution of a given set of data is important since most parametric statistical tests are based on the assumption that the studied data are normal distributed. In analysis of fracture mechanics the Weibull distribution is widely used and the derived Weibull modulus is interpreted as a material constant. However, the estimation of this parameter is laborious and subject to estimation problems. It is shown that the Weibull modulus is inherently connected to the coefficient of variation and that the information obtained from the modulus is unclear. The distribution of crushing strength data from nine model tablet formulations and four commercial tablets are shown to follow the normal distribution. The importance of proper cleaning of the crushing strength apparatus is demonstrated.


PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus.
Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQR11 of the progestin and AdipoQ receptors family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state. Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQR11. The simulation of ERK phosphorylation by overexpressed PAQR10/PAQR11 is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.


Sonographic diagnosis of fibromatosis.
To investigate the value of sonography in the diagnosis of fibromatosis. We retrospectively reviewed the sonographic findings, pathologic results, and other medical records of 42 patients with pathologically proven fibromatosis. The tumor's size and location were recorded. Echogenicity, margins, vascularity, and relationship with the adjacent tissue were analyzed. A total of 42 patients with 44 lesions were included in the study. In 21 patients, the tumor was a primary tumor. In 7 of these patients, a preoperative diagnosis of fibromatosis was obtained via sonographically guided biopsy or surgical biopsy. In another 21 patients, the tumor was a recurrence (including 1 case of malignant transformation). Well-defined and regular margins were demonstrated in 26 lesions (59%), whereas poorly defined and irregular borders were seen in the other 18 lesions. On Doppler imaging, vascularity was absent in 66% (29/44) lesions, moderate in 23% (10/44), and marked in 11% (5/44). Infiltration into the adjacent skeletal muscles, cortical bone, or encasement vessels, nerves, or tendons was found in 21 (48%) lesions. In patients with fibromatosis, sonography demonstrates a nonspecific hypoechoic solid mass and can guide the percutaneous needle biopsy.


A Shared Medical Appointment on the Benefits and Risks of Opioids Is Associated With Improved Patient Confidence in Managing Chronic Pain.
To evaluate a shared medical appointment (SMA) on opioids in the treatment of chronic pain. This prospective study was conducted at an ambulatory clinic within a health-care delivery system. The SMA is a single 90-minute encounter, led by a physician. We included adult patients who attended the SMA and completed an immediate pre-post survey. Survey items were measured on a scale from 0 (worst) to 5 (best). Mean differences in pre-post responses were assessed by a paired t test. A total of 130 patients were included in the analysis. Patients showed improvements in confidence in self-managing pain (+0.44; 95% confidence interval [CI]: 0.29-0.59; P < .001) and their providers' ability to help manage pain (+0.28; 95% CI: 0.14-0.43; P < .001). Most patients (81%) were very/extremely satisfied with the SMA. An SMA on the benefits and risks of opioids was associated with prompt improvements in patients' confidence in self-managing pain and in their health-care providers' ability to help manage pain. Such confidence can lay the foundation for increased patient engagement and activation in pain management.