The level of urinary α1 microglobulin excretion is a useful marker of peritubular capillaritis in antineutrophil cytoplasmic antibody associated vasculitis.
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis affects small vessels in the kidney (i.e., arterioles, glomerular or peritubular capillaries, or venules). Although crescentic glomerulonephritis is a common histological finding, the incidence of peritubular capillaritis (PTC) or arteriolitis is unclear. Moreover, the laboratory data that reflect the degree of renal histological damage and distinguish between PTC and arteriolitis have not yet been clarified. We investigated laboratory data and histological findings from 11 patients diagnosed with ANCA-associated vasculitis (2 men and 9 women, mean age 70.3 ± 3.3 years) whose renal biopsies were performed between 2009 and 2014. All patients were positive for myeloperoxidase (MPO)-ANCA. PTC or arteriolitis was detected in six patients (54.5 %), respectively. The only significant positive relationship between laboratory data and histological findings observed was that between levels of urinary α1 microglobulin (u-α1MG) excretion and the percentage of tubular atrophy and interstitial fibrosis (r = 0.67, p = 0.035). No significant differences in laboratory data were found between patients with or without arteriolitis. However, the levels of u-α1MG excretion were significantly higher in patients with PTC than in those without PTC (75.2 ± 19.5 vs. 15.0 ± 3.6 mg/dl, p = 0.035). PTC or arteriolitis occurs at a high rate independently of crescentic glomerulonephritis in ANCA-associated vasculitis patients. The levels of u-α1MG excretion reflect the degrees of tubular atrophy and interstitial fibrosis. Moreover, high levels of u-α1MG excretion suggest that PTC is more likely than arteriolitis in ANCA-associated vasculitis patients.


Effect of benzyladenine on recovery of cryopreserved shoot tips of grapevine and citrus cultured in vitro.
The effect of N6-benzyladenine (BA) on the recovery of cryopreserved shoot tips of the LN33 hybrid (Vitis L.) and Troyer citrange [Poncirus trifoliata (L.) Raf. x Citrus sinensis [L.] Osbeck.] cultured in vitro was examined. For the LN33 hybrid, the presence of BA in the recovery medium was essential for survival of control and cryopreserved shoot tips, although the BA concentration did not influence the survival percentage. BA at 5, 2, and 5 microM or higher induced callus formation in control, and shoot tips cryopreserved by vitrification, and by encapsulation-dehydration, respectively. While a BA concentration of 4 microM was found optimal for recovery of control shoot tips, 1 and 2-4 microM produced the best recovery of shoot tips cryopreserved by vitrification and encapsulation-dehydration, respectively. A similar pattern of effect of BA on recovery was found for 'Troyer' citrange. Low survival of control and cryopreserved shoot tips was observed with a BA-free recovery medium. The addition of BA to the recovery medium significantly increased survival. The BA concentration that induced callus formation in shoot tips cryopreserved by encapsulation-vitrification was higher than that which induced it in those cryopreserved by encapsulation-dehydration. Recovery of control shoot tips was best with an addition of 6-10 microM BA to the medium. Optimal recovery of shoot tips cryopreserved by encapsulation-vitrification and encapsulation-dehydration was achieved with 3-4 and 2 microM BA, respectively. Results from the present study suggest that an optimal BA concentration for recovery of control shoot tips may be different from that for cryopreserved shoot tips; furthermore, the optimal BA concentration for recovery of cryopreserved shoot tips may also differ among different cryogenic procedures.


[Incidence of thrombi in implantation of pulmonary artery catheters].
To evaluate the occurrence of thrombi in introducers employed for pulmonary artery catheterization. prospective study. cardiac Surgery ICU in a University Hospital. three groups of 20 subjects each: in group A, undergoing mitral or aortic valve replacement, a pulmonary artery catheter was placed through an introducer; in group B, undergoing myocardial revascularization, a pulmonary artery catheter was placed through an introducer; in group C, undergoing myocardial revascularization, only an introducer was placed. The introducers were removed between the 2nd and the 8th postoperative day and the external surface and the lumen were inspected for thrombi. Endoluminal thrombi were observed in 40% of the introducers, but the patency of the lumen was always maintained. The incidence of thrombi was significantly higher in group A (23% in aggregate) than in group B (10%; p < 0.05) and in group C (6%; p < 0.05); by contrast no significant difference was observed between groups B and C. Endoluminal thrombi are very frequent in introducers employed for pulmonary artery catheterization but they are hardly suspected since the patency of the lumen is usually preserved. The lower incidence of thrombosis in groups B and C could hypothetically originate from antiaggregant therapy started within 24 hours from the end of surgery for myocardial revascularization.


Small bowel volvulus with jejunal diverticulum: Primary or secondary?
Small bowel volvulus, which is torsion of the small bowel and its mesentery, is a medical emergency, and is categorized as primary or secondary type. Primary type often occurs without any apparent intrinsic anatomical anomalies, while the secondary type is common clinically and could be caused by numerous factors including postoperative adhesions, intestinal diverticulum, and/or tumors. Here, we report a rare case of a 60-year-old man diagnosed with small bowel volvulus using multidetector computed tomography (MDCT) angiography. Further discovery by laparotomy showed one jejunal diverticulum, longer corresponding mesentery with a narrower insertion, and a lack of mesenteric fat. This case report includes several etiological factors of small bowel volvulus, and we discuss the possible cause of small bowel volvulus in this patient. We also highlight the importance of MDCT angiography in the diagnosis of volvulus and share our experience in treating this disease.


Rh(I)-Catalyzed Intramolecular Decarbonylation of Thioesters.
Decarbonylative synthesis of thioethers from thioesters proceeds in the presence of a catalytic amount of [Rh(cod)Cl]2 (2 mol %). The protocol represents the first Rh-catalyzed decarbonylative thioetherification of thioesters to yield valuable thioethers. Notable features include the absence of phosphine ligands, inorganic bases, and other additives and excellent group tolerance to aryl chlorides and bromides that are problematic using other metals to promote decarbonylation. Gram scale synthesis, late-stage pharmaceutical derivatization, and orthogonal site-selective cross-couplings by C-S/C-Br cleavage are reported.


Multiple cerebral aneurysms in identical twins.
We report the finding of multiple cerebral aneurysms in a pair of identical twins. One twin had subarachnoid hemorrhage and intracerebral hematoma; her sister had subarachnoid hemorrhage and intraventricular bleeding. Angiography in both cases showed multiple cerebral aneurysms. It is appropriate to recommend a cerebral angiographic examination of an asymptomatic twin after the other twin has suffered an aneurysmal subarachnoid hemorrhage.


The reliability and validity of the Turkish version of the school-based asthma and allergy screening questionnaires.
Asthma is an important public health disease affecting children that may result in school absenteeism and hospitalization. This study aims to assess the validity, reliability, and diagnostic accuracy of the Turkish version of the asthma and allergy screening questionnaire. This study included primary and secondary school students from grades 2 to 7 and their parents or caregivers. For validity, 40 children with asthma and 39 children with allergies diagnosed by the questionnaire were used to determine the sensitivity. The specificity was calculated by using the data of 100 children without asthma and allergies. The study was completed with the participation of 704 students and parents. The intraclass correlation coefficient (ICC) was used to assess item reliability. Receiver operating characteristic (ROC) analysis was used to assess validity. When the cutoff point of the questionnaire was 2/3 for asthma, the sensitivity was 80.0% and 82.5% and the specificity was 56.6% and 76.8% according to the student and parent form, respectively. When the cutoff point of the questionnaire was 0/1 for allergies, the sensitivity was 74.4% and 84.6% and the specificity was 66.3% and 54.2% according to the student (SQ) and parent questionnaire (PQ), respectively. The reliability of test-retest correlation values (≥0.68) of asthma and allergy questionnaires were found to be statistically significant. The internal consistency Cronbach's α values of the asthma SQ and PQ were 0.72 and 0.80, respectively. According to the Turkish questionnaire for students and their parents, the sensitivity of asthma and allergy questionnaires was similar in proportion to the original questionnaire. The Turkish version of the questionnaire can be used for asthma and allergy screening in schools.


Lymphatics in primary cutaneous melanoma.
Using Ulex europaeus I lectin (UEA1) to demonstrate endothelial cells, we have previously shown that frequency of capillary invasion correlates closely with maximum tumor thickness in primary cutaneous melanoma. UEA1 demonstrates both vascular and lymphatic capillaries; however, only vascular capillaries possess basement membranes. In order to ascertain whether these capillaries were lymphatic or vascular, we employed a double staining technique, using UEA1 in conjunction with a monoclonal anti-type IV collagen antibody. We studied 21 primary cutaneous melanomas. Seven of the 21 included lymphatic capillaries, while 14 did not. These lymphatic capillaries were very sparse and appeared to be residual dermal lymphatics rather than a result of lymphangiogenesis. Lymphatic permeation by melanoma was not seen in any of the tumors studied. There was no apparent association among tumor thickness, level of invasion, growth phase, necrosis, regression or mitotic index, and presence of lymphatics within the melanomas. Although scanty lymphatics are present in some primary cutaneous melanomas, this study does not suggest that lymphatic permeation plays a major role in the spread of melanoma to locoregional lymph nodes.


Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review.
Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota. To examine the conduct and reporting of studies assessing FMT. Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017. Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT. Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention. Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non-randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition. Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting. Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported. No specific funding.


Chlamydia trachomatis pneumonia in adults: radiographic appearance.
Radiographic findings in six adults with evidence of community-acquired Chlamydia trachomatis pneumonia were studied. Streaky infiltration, without evidence of consolidation, and multilobar involvement were characteristic. Radiographic features that distinguish this unique entity from other community-acquired pneumonias and from Chlamydia trachomatis pneumonia in infancy are also discussed.


Social networks and mental health in post-conflict Mitrovica, Kosova.
To investigate the relation between social networks and mental health in the post-conflict municipality of Mitrovica, Kosovo. Using a three-stage stratified sampling method, 1239 respondents aged 16 years or above were recruited in the Greater Mitrovica region. Social network depth was measured by the frequency of contacts with friends, relatives and strangers. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression was used to examine the association between social network depth and mental health. The analytical sample consisted of 993 respondents. The prevalence of depression (54.3%) and anxiety (64.4%) were extremely high. In multiple regression analysis, a lower depth of social network (contact with friends) was associated with higher levels of both depression and anxiety. This study has shown that only one variety of social network--contact with friends--was important in terms of mental health outcomes in a population living in an area heavily affected by conflict. This suggests that the relation between social networks and mental health may be complex in that the effects of different forms of social network on mental health are not uniform and may depend on the way social networks are operationalised and the particular context in which the relationship is examined.


Clinical Validation of a CXCR4 Mutation Screening Assay for Waldenstrom Macroglobulinemia.
Waldenstrom macroglobulinemia (WM) is a B-cell lymphoma characterized by the accumulation of lymphocytes and plasmacytic cells in the bone marrow and by excess production of immunoglobulin M in serum. WM has been closely linked with the MYD88(L265P) mutation. Whole genome sequencing has identified somatic mutations in the CXCR4 gene in ∼29% of WM cases with MYD88(L265P). CXCR4 mutations may interfere with treatment response to ibrutinib. The goal of this study was to design and validate a clinical assay to detect CXCR4 mutations. Thirty-three low-grade B-cell lymphomas with plasmacytic differentiation (23 MYD88(L265P) and 10 MYD88(WT)) involving various samples types (fresh and formalin-fixed tissues) formed the study group. We designed and validated Sanger sequencing and pyrosequencing assays to detect mutations in CXCR4 in a Clinical Laboratory Improvement Amendments-approved clinical laboratory. We identified 8 cases with CXCR4 mutations, including 5 single nucleotide substitutions (3 resulting in p.S338* and 1 in p.R334*), and 3 insertion/deletions. Seven of 8 CXCR4 mutated cases were also MYD88(L265P) mutant. Among the single nucleotide substitutions, we identified a novel missense variant (p.L326P) and a previously reported variant (G335S) of uncertain clinical significance. We successfully validated a set of clinical assays to detect mutations in CXCR4 mutations in a clinical laboratory.


The Expression of Gli3 and Teashirt3 in the Stenotic Tissue of Congenital Pelvi-Ureteric Junction Obstruction in Children.
The aim of this study was to determine the expression pattern of Gli3 and Teashirt3 in stenotic segments in children with congenital hydronephrosis due to pelvi-ureteric junction obstruction (PUJO) versus in normal control subjects. 60 patients and 10 controls were included in this study. Immunohistochemistry, Western blot and real-time PCR were used to investigate into the expression of Gli3 and Teashirt3. Immunohistochemistry identified that Gli3 and Teashirt3 located in the cytoplasm of smooth muscle in normal ureter. However, the expression of Gli3 and Teashirt3 was negative in the PUJO group. Gli3 and Teashirt3 protein and mRNA expression was significantly decreased in PUJO group compared with control group on Western blot and real time PCR. The expression of protein and mRNA of Gli3 and Teashirt3 was significantly decreased in the PUJO group. Gli3 and Teashirt3 protein was mainly located in the cytoplasm of smooth muscle in normal ureter. Gli3 and Teashirt3 might play an important role in the normal development of the ureter. The down-regulated Gli3 and Teashirt3 perhaps participated in the pathogenesis of the congenital hydronephrosis due to PUJO.


The application of tris buffer and copper sulfate for the preservation of phenylurea pesticides analyzed using U.S. EPA method 532 in the UCMR Survey.
A high performance liquid chromatographic method was developed to meetthe U.S. Environmental Protection Agency's (EPA) Unregulated Contaminant Monitoring Rule (UCMR) Survey need for the analysis of phenylurea pesticides in drinking waters. Many of these phenylurea compounds were demonstrated to degrade rapidly in the presence of the residual chlorine disinfectant in drinking waters. This degradation was halted by the addition of a tris buffer, which was initially chosen to optimize the sample pH prior to extraction. Copper sulfate was found to prevent the regrowth of microorganisms in surface waters, which was observed upon dechlorination. Tris buffer provided the additional benefit of keeping the copper sulfate preservative in solution even in groundwater matrices that caused precipitation of copper in its absence. A C18 solid phase, in cartridge or disk form, was used to efficiently extract target compounds from the preserved drinking water matrices. A 21-day storage stability study, together with precision and accuracy studies, demonstrated thatthis method had suitable sensitivity, selectivity, accuracy, precision, and ruggedness for use in the EPA's UCMR drinking water occurrence survey.


Idiopathic pontine Streptococcus salivarius abscess in an immunocompetent patient: management lessons through case illustration and literature review.
A 55-y-old woman with no previous medical history presented with a 3-day history of progressive headache, nausea, emesis, right-sided facial numbness, and right-sided extremity weakness. Serial magnetic resonance imaging demonstrated rapid enlargement of a left-sided ring-enhancing dorsal pontine lesion with an exophytic portion, raising concern for an abscess. A stereotactically guided left-sided retrosigmoid craniotomy for abscess incision and decompression was performed given the rapid progression of her neurological deficits. Streptococcus salivarius was isolated from the intra-operative samples. After an extensive evaluation, no source for the S. salivarius was identified. Solitary brainstem abscesses are uncommon intracranial infections with high morbidity and mortality. Patients can present with non-specific symptoms and often have no previous medical history. Since 1974, 40 patients with solitary brainstem abscess have survived to hospital discharge. We outline management strategies for solitary brainstem abscess based on a literature review of survivors.


Variable Expression of Opa Proteins by Neisseria gonorrhoeae Influences Bacterial Association and Phagocytic Killing by Human Neutrophils.
Neisseria gonorrhoeae infection is characterized by local and abundant recruitment of neutrophils. Despite neutrophils' antimicrobial activities, viable N. gonorrhoeae is recovered from infected individuals, leading to the question of how N. gonorrhoeae survives neutrophil attack. One feature impacting N. gonorrhoeae-neutrophil interactions is the phase-variable opacity-associated (Opa) proteins. Most Opa proteins engage human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) to facilitate bacterial binding and invasion. Neutrophils express two transmembrane CEACAMs, CEACAM1 and the granulocyte-specific CEACAM3. While N. gonorrhoeae isolated from infected individuals is frequently Opa+, expression of OpaD from strain FA1090, which interacts with CEACAMs 1 and 3, is associated with reduced N. gonorrhoeae survival after exposure to human neutrophils. In this study, we hypothesized that the receptor-binding capability of individual Opa proteins impacts bacterial survival in the presence of neutrophils. To test this hypothesis, we introduced opa genes that are constitutively expressed into a derivative of strain FA1090 with all 11 opa genes deleted. The engineered genes encode Opa proteins that bind CEACAM1 and -3, CEACAM1 but not CEACAM3, or neither CEACAM1 nor -3. N. gonorrhoeae expressing CEACAM3-binding Opa proteins survived significantly less well than bacteria expressing other Opa proteins when exposed to primary human neutrophils. The CEACAM3-binding N. gonorrhoeae had significantly greater association with and internalization by neutrophils. However, once internalized, bacteria were similarly killed inside neutrophils, regardless of Opa expression. Furthermore, Opa expression did not significantly impact neutrophil granule mobilization. Our findings indicate that the extent to which Opa proteins mediate nonopsonic binding is the predominant determinant of bacterial survival from neutrophils. IMPORTANCE Neisseria gonorrhoeae, the cause of gonorrhea, is an urgent-threat pathogen due to increasing numbers of infections and increased antibiotic resistance. Many surface components of N. gonorrhoeae are phase variable, including the Opa protein family of adhesins and invasins. While Opa protein expression is selected for in vivo, bacteria expressing some Opa proteins are readily killed by neutrophils, which are recruited to sites of infection. The reason for this discrepancy has remained unresolved. Our work shows that Opa-dependent differences in bacterial survival after exposure to primary human neutrophils correlates with Opa-dependent bacterial binding and phagocytosis. These findings underscore how the ability of N. gonorrhoeae to change Opa expression through phase variation contributes to bacterial resistance to neutrophil clearance.


Increased metabotropic glutamate 2/3 receptor binding in the perigenual anterior cingulate cortex of Cloninger type 2 alcoholics: a whole-hemisphere autoradiography study.
Metabotropic glutamate receptors 2 and 3 (mGluR2/3) contribute to control the level of glutamate in the synapse. In rodents, mGluR2/3 agonists attenuate the reinstatement of alcohol-seeking behavior. Linking possible alterations of the mGluR2/3 system to the etiology and type of alcoholism could provide valuable information for the development of novel mGluR2/3 function modulating therapies in addiction treatment. To date, mGluR2/3 binding density has not been studied in human alcoholics. We aimed to investigate the possible differences in mGluR2/3 binding between Cloninger type 1 anxiety-prone and type 2 impulsive alcoholics and controls. We performed a post-mortem whole-hemisphere autoradiography to study the mGluR2/3 binding density of 9 type 1 alcoholics, 8 type 2 alcoholics and 10 controls. [(3)H]LY341495, a potent group II metabotropic glutamate receptor antagonist, was used as the radio-ligand with l-glutamate as a displacer. [(3)H]LY341495 binding density was statistically significantly increased (P = 0.046) in the perigenual anterior cingulate cortex (pACC) of type 2 alcoholics when compared with controls. In other brain areas, no significant difference between the groups was found. This preliminary study suggests that impulsive type 2 alcoholics might have alterations in the mGluR2/3 function in the pACC, a brain area presumed to be involved in the control of drug-seeking behaviors and self-control.


Intrathecal midazolam combined with low-dose bupivacaine improves postoperative recovery in diabetic mellitus patients undergoing foot debridement.
Intrathecal midazolam acts synergically with other anesthetics to relieve surgical pain, and the drug combination may decrease complications attributable to each component drug. This prospective study was to determine the spinal effects of low-dose of bupivacaine (5 mg) combined with intrathecal midazolam (2 mg) in diabetes mellitus (DM) patients undergoing foot debridement. Sixty diabetic patients were admitted for foot debridement under spinal anesthesia were equally divided into two groups. Group 1 (M) received 7.5 mg of hyperbaric bupivacaine; group 2 (M+M) received 5 mg of hyperbaric bupivacaine combined with 2 mg of midazolam intrathecally. The intensity of motor block was assessed with modified Bromage scale 20 minutes after injection, and at 0, 30, 60, 90 and 120 min after arriving at the post anesthesia care unit (PACU). Pain score was assessed with a 10 cm visual analog scale (VAS, 0 = no pain and 10 = intolerable pain) at 0, 1, 2, 6 h and 24 h postoperatively. Anesthesia was smooth in all patients except one in group M, whose analgesia was inadequate and general anesthesia was given to complete the surgery. The number of patients who sustained moderate to severe pain (VAS > 5) was significantly less in the M+M group than in M group as accessed 6 and 24 h postoperatively. The requirement of additional analgesic as reinforcement was significantly less in the M+M group than in the M group within the space of 24 h postoperatively. Recovery of motor function was significantly faster in the M+M group. The combination of intrathecal midazolam and bupivacaine was a safe and effective anesthetic technique, and it also provided early recovery of motor function and reduced the requirement of analgesics postoperatively.


Serotonin and substance P coexist i, neurons of the rat's central nervous system.
5-Hydroxytryptamine (serotonin)-containing neurons in the rat's medullary raphe and interfascicularis hypoglossi cell groups were identified by means of autoradiography following prolonged intraventricular administration of 5-hydroxy[(3)H]tryptamine, fluorescence histochemistry for the demonstration of endogenous 5-hydroxytryptamine, and microspectrofluorimetric analysis of excitation and emission spectra. Immunocytochemical methods (the unlabeled primary antibody-peroxidase antiperoxidase and indirect immunofluorescence methods) were applied with antisera to substance P in order to localize immunoreactivity in these medullary neurons. It was demonstrated that the raphe nuclei and the interfascicularis hypoglossi nucleus are heterogeneous cell groups that contain: (i) Neurons that display both an uptake-storage capacity for 5-hydroxy[(3)H]tryptamine and a formaldehyde-induced fluorescence with spectral characteristics identical to those of the 5-hydroxytryptamine fluorophor. These cells exhibit high to low fluorescence intensities without detectable substance P-like immunoreactivity. (ii) Neurons with various 5-hydroxytryptamine fluorescence intensities and intense to low degrees of substance P-like immunoreactivity. (iii) Neurons with various degrees of substance P-like immunoreactivity without detectable 5-hydroxytryptamine fluorescence or 5-hydroxy[(3)H]tryptamine uptake and storage capacity. These results indicate that some neurons contain high or low levels of only 5-hydroxytryptamine or substance P, whereas other neurons contain both 5-hydroxytryptamine and substance P in various proportions. The present findings demonstrate the presence of two putative transmitters, a biogenic amine and a polypeptide, within the same neuron in the mammalian central nervous system.


Mutagenicity of red wine in the L-arabinose resistance test with Salmonella typhimurium.
The forward mutation assay to L-arabinose resistance (Ara test) in Salmonella typhimurium detected a Spanish red table wine (Rioja) as a direct-acting mutagen. The best mutagenic response was obtained by preincubating strain BA13 with the wine sample in the presence of sodium phosphate buffer and in the absence of any external metabolic activation. In fact, the S9 mixture abolished most of the mutagenic activity of red wine in the Ara test. Such an inactivating capacity seems to be independent of microsomal enzymes and mediated through some kind of heat-stable component(s) in the S9 fraction. Both regular wine (directly from the bottle) and lyophilized wine were strong mutagens in the Ara test, inducing 4914 and 2739 AraR mutants/ml. Both pKM101 and delta uvrB were critical factors in the detection of the mutagenicity of wine, exhibiting a synergic effect in strain BA13. The mutagenicity of red wine was somehow pH-dependent, increasing with the pH value of the preincubation mixture. In comparison with the Ara test, the His reverse mutation assay (Ames test) was much less sensitive to the mutagenicity of lyophilized red wine, TA102 being the most (448 His+/ml) and TA98 the least (38 His+/ml) sensitive strain. TA100, TA104 and TA97 manifested intermediate mutagenicities to red wine. Previous reports have identified strain TA98 as the His strain most sensitive to the apolar fraction (e.g. XAD-2-bound) of red wine. Based on these results we propose that TA98 mainly detects glycosides of mutagenic flavonols present in red wine (quercetin, rutin, etc.), which do not constitute the major direct-acting mutagens detected with the Ara test.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of thyroid status and thyrostatic drugs on hepatic glucuronidation of lodothyronines and other substrates in rats : Induction of phenol UDP-glucuronyltransferase by methimazole.
Glucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but the effect of thyroid status on hepatic glucuronidation of iodothyronines is unknown. We examined the effects of hypothyroidism induced by treatment of rats with propylthiouracil (PTU) or methimazole (MMI) or by thyroidectomy as well as the effects of T4-induced hyperthyroidism on the hepatic UGT activities for T4, T3, bilirubin,p-nitrophenol (PNP), and androsterone. Bilirubin UGT activity was increased in MMI- or PTU-induced hypothyroid and thyroidectomized rats, and decreased in hyperthyroid animals. T4 and, to a lesser extent, T3 UGT activities were increased in MMI- or PTU-induced hypothyroid rats, and T4 but not T3 glucuronidation also showed a significant increase in thyroidectomized rats. T4 but not T3 UGT activity was slightly decreased in hyperthyroid rats. While PNP UGT activity was decreased in thyroidectomized rats and increased in hyperthyroid animals, it was also markedly increased by MMI and slightly increased by PTU-induced hypothyroidism. In T4-substituted rats, MMI did not affect T4, T3, bilirubin and androsterone UGT activities but again strongly induced PNP UGT activity, indicating that this represented a direct induction of PNP UGT by the drug independent of its thyrostatic action. Androsterone UGT activity was hardly affected by thyroid status. Our results suggest a modest, negative control of the hepatic glucuronidation of thyroid hormone by thyroid status, which may be mediated by changes in bilirubin UGT activity. To our knowledge, this is the first report of the marked induction of a hepatic enzyme by MMI, which is not mediated by its thyroid hormone-lowering effect.


Protective Effects of Chlorogenic Acid against Experimental Reflux Esophagitis in Rats.
Esophageal reflux of gastric contents causes esophageal mucosal damage and inflammation. Recent studies show that oxygen-derived free radicals mediate mucosal damage in reflux esophagitis (RE). Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and possesses anti-inflammatory, antibacterial and anti-oxidant activities. In this context, we investigated the effects of CGA against experimental RE in rats. RE was produced by ligating the transitional region between the forestomach and the glandular portion and covering the duodenum near the pylorus ring with a small piece of catheter. CGA (10, 30 and 100 mg/kg) and omeprazole (positive control, 10 mg/kg) were administered orally 48 h after the RE operation for 12 days. CGA reduced the severity of esophageal lesions, and this beneficial effect was confirmed by histopathological observations. CGA reduced esophageal lipid peroxidation and increased the reduced glutathione/oxidized glutathione ratio. CGA attenuated increases in the serum level of tumor necrosis factor-α, and expressions of inducible nitric oxide synthase and cyclooxygenase-2 protein. CGA alleviates RE-induced mucosal injury, and this protection is associated with reduced oxidative stress and the anti-inflammatory properties of CGA.


Factors associated with referral to medical oncology and subsequent use of adjuvant chemotherapy for non-small-cell lung cancer: a population-based study.
Adjuvant chemotherapy (act) for non-small-cell lung cancer (nsclc) is associated with improved survival in the general population, but may be underutilized. We explored the factors associated with referral to medical oncology and subsequent use of act among all patients with resected nsclc in Ontario, Canada. The Ontario Cancer Registry was used to identify all incident cases of nsclc diagnosed in Ontario during 2004-2006. We linked electronic records of treatment and of physician billing to identify surgery, act, and medical oncology consultation. A multivariate logistic regression model was used to evaluate factors associated with referral to medical oncology and subsequent use of act. Among 3354 cases of nsclc resected in Ontario during 2004-2006, 1830 (55%) were seen postoperatively by medical oncology, and 1032 (31%) were treated with act. Patients more than 70 years of age were less likely than younger patients to have a consultation [odds ratio (or): 0.4; p < 0.001]. A higher proportion of cases with stage ii or iii nsclc than with stage i disease were referred (ors: 2.7, 2.0 respectively; p < 0.005). We observed substantial geographic variation in the proportion of surgical cases referred (range: 32%-88%) that was not explained by differences in case mix. Among cases referred to medical oncology, older patients (age 60-69 years, or: 0.4; age 70+ years, or: 0.1; p < 0.001) with greater comorbidity (Charlson comorbidity index: 3+; or: 0.5; p < 0.05) and a longer postoperative stay (median length of stay: 7+ days; or: 0.7; p = 0.001) were less likely to receive act. Use of act was greater in patients with stage ii or iii than with stage i disease (ors: 3.0, 2.7 respectively; p < 0.001); use also varied with geographic location (range: 46%-63%). The initial decision to refer to medical oncology is associated with age and stage of disease, and those factors have an even greater effect on the decision to offer act. Comorbidity and postoperative length of stay were not associated with initial referral, but were associated with use of act in patients seen by medical oncology.


A classification of contour deformities after bariatric weight loss: the Pittsburgh Rating Scale.
Contour deformities after massive weight loss are diverse and often severe in nature. Current progress has necessitated a valid, accessible, and comprehensive rating system that correlates appearance and appropriate surgical treatment. Presently, no existing rating system addresses the breadth and variety of deformities that can occur or allows for adequate postsurgical evaluation. The authors reviewed full-body photographs of over 300 female patients seen between October of 2002 and May of 2004. The authors targeted body areas most frequently demonstrating skin and soft-tissue laxity and ptosis. A 10-region, four-point grading system was designed to describe the common deformities found in each region of the body. To validate the scale, 12 trained observers applied the rating scale to photographs of 25 patients who showed the 10 regions. Each grading scale ranged from 0, indicating normal, to 3, indicating the most severe deformity. Repeat testing was performed at 2 weeks. Interobserver validity and test-retest reliability were determined using weighted kappa analysis. In all 10 categories, the kappa value was 0.6 or higher (0.6 = threshold for good validity), with a mean kappa value of 0.68 (range, 0.61 to 0.78) and an overall agreement of 69 percent over two sessions. All 12 observers scored an individual mean kappa value of greater than 0.6, indicating good interobserver validity. A given observer had a mean 67 percent agreement, indicating reasonable test-retest reliability. The Pittsburgh Rating Scale is a validated measure of contour deformities after bariatric weight loss. This scale may have applications in preoperative planning and evaluating surgical outcomes.


FITNESS CONSEQUENCES OF MATING SYSTEM, SEED WEIGHT, AND EMERGENCE DATE IN A WINTER ANNUAL, COLLINSIA VERNA.
Selfed and outcrossed progeny of 60 maternal parents were produced to investigate the joint and individual effects of mating system, seed weight, and emergence date on the expression of characters related to fitness and adult fecundity. A series of analyses of variance investigated these effects through time and indicated that 1) mating system explained 56% of the variance in seed weight, 2) seed weight explained 51% and mating system explained 38% of the variance in emergence date, and 3) mating system explained 71% and seed weight explained 15% of the variance in fecundity. Outcrossed-seed means differed significantly from selfed-seed means for all traits measured. On average, outcrossed seeds were larger, germinated earlier, had higher percentage emergence, and produced plants that were more fecund than selfed seeds. The coefficient of inbreeding depression increased through time in this study, from 0.05 for seed weight to 0.23 for fecundity. Seed weight and emergence date were positively correlated, both phenotypically and genetically, for both mating systems. Genetically, this indicates that genes that increase the value of seed weight also increase the value of emergence date and vice versa. Phenotypically, the positive correlation indicates that larger seeds germinate later. Outcrossed seeds were significantly larger but germinated earlier than selfed seeds, suggesting that mating system has an overriding effect in influencing fitness. In light of the selection on emergence date quantified in a previous study, seed weight, emergence date, and mating system may be functioning as a cluster of characters on which selection acts jointly in this species.


[Unusual historical cases of uterine inversion].
Professor Martial Dumont presents four cases of inverted uterus which are quite old. They come from the book by Mr Planque, M.D., entitled: "Selected Medical Library, from periodical publications, French as well as Foreign", published in Paris in 1748, by D'Houry senior, publisher and bookseller of His Royal Highness the Duke of Orleans, rue de la Vieille Boucherie. These findings are reported in Volume One, pages 406-413.


Mental health outcomes in a population-based cohort of patients with prostate cancer.
Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer. Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided. The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P < .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis. Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer.


Dependence of Raman and resonance Raman intensities on sample self-absorption.
Resonance Raman cross sections are generally larger than normal or preresonance Raman cross sections. Thus, higher Raman intensities are expected for resonance excitation, especially for backscattering measurements. However, self absorption decreases the observed Raman intensities. In the work here we examine the effect of self absorption on the observed preresonance and resonance Raman intensities. For the simplest case where a single electronic transition dominates the Raman scattering, and where the resonance enhancement scales with the square of the molar absorptivity of the absorption band, theory predicts that for close to resonance excitation the observed Raman intensities monotonically increase as resonance is approached. In the case that an impurity absorbs, the observed Raman intensities may decrease as excitation moves close to resonance for particular conditions of impurity absorption band widths and frequency offsets. Impurity absorption also causes decreases in observed Raman intensities for the more slowly increasing preresonance excitation.


Plasmonically nanoconfined light probing invisible phonon modes in defect-free graphene.
We present a simple plasmonic method that enables tuning of accessibility to the dipole-forbidden transition states of matter. This technique is realized by well-controlled plasmonic dimers, which can confine optical fields on the order of molecular dimensions. As an example, the approach is applied to activate invisible noncenter phonon modes of defect-free graphene in resonance Raman spectra. The relative intensity of the normally forbidden modes with respect to the dipole allowed modes progressively increases as the degree of field confinement increases. This opens up a novel avenue for both photochemical excitation of molecular systems and nanoscale characterization of materials.


Radiographic heart volume, stroke volume and exercise cardiac frequency: relationship to body composition and other factors in healthy adult males.
Amongst 288 healthy male workers in heavy industry the radiographic heart volume was related to the fat-free mass and the percentage body fat which between them explained 27% of the variance. Exercise was performed on a treadmill using a belt speed of 80 m.min-1 (3 mph) and an incline which was increased progressively to 14% when the oxygen uptake was on average 61% of the maximum for these subjects. The exercise cardiac output was related to the uptake of oxygen, the fat-free mass and the ambient temperature; these factors accounted for 52% of the variance. The exercise stroke volume was related to the heart volume, the fat-free mass, the thigh muscle width, the ambient temperature, the Harvard Pack Index and other measurements which between them accounted for 42% of the variance. The exercise cardiac frequency was correlated negatively with the heart volume, the fat-free mass, the age and the Harvard Pack Index. The variates between them described 41% of the variance. The findings provide reference values for heart volume, stroke and exercise cardiac frequency in similar subjects.


Replantation of the heel pad.
A heel microvascular replantation was done to a 17-year-old patient. The replanted heel survived completely. A year after the operation, the patient is working in agriculture and has no problem walking.


Mapping by laser photostimulation of connections between the thalamic reticular and ventral posterior lateral nuclei in the rat.
We used laser scanning photostimulation through a focused UV laser of caged glutamate in an in vitro slice preparation through the rat's somatosensory thalamus to study topography and connectivity between the thalamic reticular nucleus and ventral posterior lateral nucleus. This enabled us to focally stimulate the soma or dendrites of reticular neurons. We were thus able to confirm and extend previous observations based mainly on neuroanatomical pathway tracing techniques: the projections from the thalamic reticular nucleus to the ventral posterior lateral nucleus have precise topography. The reticular zone, which we refer to as a "footprint," within which photostimulation evoked inhibitory postsynaptic currents (IPSCs) in relay cells, was relatively small and oval, with the long axis being parallel to the border between the thalamic reticular nucleus and ventral posterior lateral nucleus. These evoked IPSCs were large, and by using appropriate GABA antagonists, we were able to show both GABA(A) and GABA(B) components. This suggests that photostimulation strongly activated reticular neurons. Finally, we were able to activate a disynaptic relay cell-to-reticular-to- relay cell pathway by evoking IPSCs in relay cells from photostimulation of the region surrounding a recorded relay cell. This, too, suggests strong responses of relay cells, responses strong enough to evoke spiking in their postsynaptic reticular targets. The regions of photostimulation for these disynaptic responses were much larger than the above-mentioned reticular footprints, and this suggests that reticulothalamic axon arbors are less widespread than thalamoreticular arbors, that there is more convergence in thalamoreticular connections than in reticulothalamic connections, or both.


The evaluation of primary stenting of sirolimus-eluting versus bare-metal stents in the treatment of atherosclerotic lesions of crural arteries.
A comparison was made of sirolimus-eluting stents and bare stents as an effective means of treatment of stenosis in crural arteries. Patients were randomly divided into two groups: (1) patients treated with sirolimus-eluting stents and (2) patients treated with bare stents. Each group consisted of 25 patients, and every patient had one stent implanted. All patients showed symptoms of ischemia of the peripheral arteries, classified according to the Rutherford scale into categories 3, 4, and 5. All patients were examined 24 h before and 24 h and 6 months after the intervention. The results were analyzed according to clinical, hemodynamic, and angiographic criteria. Technically, the procedure was successful in 100% of cases, and both groups presented an equal improvement in clinical and hemodynamic parameters. The follow-up angiographic examination demonstrated a significantly lower rate of restenosis among the sirolimus-eluting stent group (4, 16%) versus the bare stent group (19, 76%) (p < 0.001), with lower target lesion revascularization in 3 (12%) versus 14 (56%) (p < 0.05), respectively. Quantitative angiography demonstrated that all variables used to assess restenosis were superior for sirolimus-eluting stents 6 months after intervention: late lumen loss 0.46 +/- 0.72 versus 1.70 +/- 0.94 (p < 0.001) and minimal lumen diameter 2.25 +/- 0.82 versus 0.99 +/- 1.08 (p < 0.001). Results of this study reveal that the use of sirolimus-eluting stents decreases the risk of restenosis in comparison to standard stents.


Identification of the thromboxane A2 receptor in hepatic sinusoidal endothelial cells and its role in endotoxin-induced liver injury in rats.
The presence of the thromboxane A2 receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined. The receptor was measured with a binding assay using a specific thromboxane A2 receptor antagonist, [3H]S-145. Scatchard analysis of the binding indicated the presence of a single class of high-affinity binding sites with a dissociation constant of 5.00 +/- 0.96 nmol/L, a maximal binding of 22.85 +/- 2.71 fmol/10(6) cells and 13.80 +/- 1.60 x 10(3) binding sites per cell. The addition of a cyclooxygenase inhibitor, indomethacin, during the cell preparation increased the maximal binding value and the number of binding sites of 37.34 +/- 3.01 and 22.50 +/- 1.80 x 10(3) sites/cell, respectively. The binding was displaced by various thromboxane A2 analogs such as ONO-3708 and STA2 but was not effectively competed for by other prostaglandins. Endotoxin injection reduced dissociation constant, maximal binding and the number of binding sites in sinusoidal endothelial cells to 3.49 +/- 0.87 nmol/L, 6.03 +/- 0.64 fmol/10(6) cells and 3.65 +/- 0.39 x 10(3) sites/cell, respectively. A cyclooxygenase inhibitor and a Kupffer cell inhibitor added before endotoxin treatment significantly prevented the reduction in the number of thromboxane A2 receptors. It is possible that these effects were due to a reduction in the agonist-induced internalization of the thromboxane A2 receptor brought about by the prevention of thromboxane A2 production. Preadministration of both a cyclooxygenase inhibitor and a thromboxane A2 receptor antagonist attenuated the degree of endotoxin-induced liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)


Income, Wealth and Health Inequalities - A Scottish Social Justice Perspective.
This paper considers health inequalities through a social justice perspective. The authors draw on a variety of existing sources of evidence, including experiential, scientific and contextual knowledge. The authors work with NHS Health Scotland, a national Health Board working to reduce health inequalities and improve health. Working closely with the Scottish Government and with a variety of stakeholders across different sectors, NHS Health Scotland's vision for a fairer, healthier Scotland is founded on the principles of social justice. The paper takes social justice as the starting point and explores what it means for two interlinked paradigms of social injustice-health inequality and income inequality. Utilising the wealth of evidence synthesised by NHS Health Scotland as well as drawing on the writings and evidence of philosophers, epidemiologists, the Scottish Government and international bodies, the authors explore the links between income and wealth inequality, social justice, the right to health and health inequalities. The paper ends by considering the extent to which there is appetite for social change in Scotland by considering the attitudes of the people of Scotland and of Britain to poverty, inequality and welfare.


Wavefront restoration from lateral shearing data using spectral interpolation.
Although a lateral-shear interferometer is robust against optical component vibrations, its interferogram provides information about differential wavefronts rather than the wavefronts themselves, resulting in the loss of specific frequency components. Previous studies have addressed this limitation by measuring four interferograms with different shear amounts to accurately restore the two-dimensional wavefront. This study proposes a technique that employs spectral interpolation to reduce the number of required interferograms. The proposed approach introduces an origin-shift technique for accurate spectral interpolation, which in turn is implemented by combining two methods: natural extension and least-squares determination of ambiguities in uniform biases. Numerical simulations confirmed that the proposed method accurately restored a two-dimensional wavefront from just two interferograms, thereby indicating its potential to address the limitations of the lateral-shear interferometer.


Regulation of Near-Field Radiative Heat Transfer between Multilayer BP/hBN Heterostructures.
As an allotrope of phosphorus and a promising 2D semiconductor, black phosphorus (BP) exhibits in-plane anisotropy along its armchair and zigzag crystal directions, allowing for efficient regulation of near-field radiative heat transfer (NFRHT). In this work, we investigate the NFRHT between two multilayer BP/hBN heterostructures and theoretically demonstrate that thermal regulation can be realized by tuning the electron density and rotation angle of BP. Results show that a larger electron density leads to the coupling of anisotropic surface plasmon polaritons (SPPs) of BP with hyperbolic modes of hBN, and rotation of BP changes the anisotropic characteristic of coupled SPPs on both sides, whereby a regulation ratio of 5.8 can be obtained. We also analyze the effects of period number, hBN layer thickness, and topmost-layer material on the NFRHT. This work may be beneficial for efficient nanoscale thermal management and physical understanding of radiative heat transfer based on anisotropic SPPs.


Voluntary Assisted Dying by Practitioner Administration Is Not Suicide: A Way Past the Commonwealth Criminal Code?
Five Australian States - Victoria, Western Australia, Tasmania, South Australia and Queensland - have now legalised voluntary assisted dying (VAD). These State legislative schemes intersect with provisions in the Criminal Code Act 1995 (Cth) (Commonwealth Criminal Code) which prohibit using electronic communication to counsel, promote, or provide instruction on "suicide". These provisions may prevent some conversations and assessments relating to self-administration of VAD occurring via telehealth, thereby restricting access for prospective VAD patients in regional and remote areas. However, as practitioner administration of VAD is not "suicide", the Commonwealth Criminal Code does not apply. The Commonwealth law creates the absurd result that the same conversation conducted via telehealth is illegal when contemplating VAD by self-administration, but legal when discussing practitioner-administered VAD. To avoid this, we advocate amending the Code to remove the inconsistency with state VAD laws. We also recommend State legislatures consider permitting greater access to VAD by practitioner-administered VAD.


Ultrasonic and biochemical evaluation of human diabetic lens.
To evaluate the ultrasonic attenuation and amount of soluble proteins of human diabetic lens. The examination was performed in the Clinic of Eye Diseases of Kaunas University of Medicine. The study included 4 groups of patients (110 eyes). The first group consisted of healthy subjects (32 eyes), the second group--of patients with initial senile cataract (13 eyes), the third group--patients with type I diabetes mellitus (24 eyes) and the fourth group--patients with type II diabetes mellitus (41 eyes). In vivo examination of human lenses was carried out by Mentor A/B ultrasonic imaging system using 7 MHz A-mode probe and the ultrasound attenuation coefficient was calculated. The phacoemulsification technique has been used for cataract extraction. Gel chromatography of the supernatant fraction on the Sepharose CL 6B column was used for fractionation of soluble lens proteins. Protein concentration was determined by the method of Lowry using bovine serum as standard. The least mean lens thickness of 3.58+/-0.18 mm was found in the healthy patients' group. There was a significant difference (p<0.05) between the thicknesses of the lenses in the healthy group and in the type I diabetic group. The difference between senile cataract and type II diabetic cataract was insignificant (p>0.05). The mean ultrasound attenuation coefficient in the groups of healthy and type I diabetic cataract was nearly the same, as so as in the groups of senile cataract and type II diabetic cataract. The significant difference (p<0.001) in the values of attenuation coefficient was found between the groups of type I and type II diabetics. The amount of soluble proteins was lowest in cataractous lenses of patients with type II diabetes (0.053+/-0.007 mg/1 mg tissue) and highest in the lenses of patients with type I diabetes (0.063+/-0.004 mg / 1 mg tissue), but those differences were statistically insignificant. Distribution of soluble proteins into the different molecular mass fractions in the group of type I diabetic lenses was found to be similar to the type II diabetic lenses and to the patients with senile cataract. The diabetic changes stronger influence the thickness of lenses of young people; in the elder age the difference between the thickness of senile and diabetic cataract is not so distinct. Ultrasound attenuation coefficient has a tendency to be higher in patients with senile and type II diabetic cataract. Human lens crystallins of patients with type I diabetes and type II diabetes are damaged at the same degree, the amount of soluble proteins decrease with age and biochemical changes of the lens.


Ciproxifan attenuates the memory impairment induced by lipopolysaccharide through modulation of cholinergic transmission in the mouse brain.
We investigated the protective effect of ciproxifan on lipopolysaccharide (LPS)-induced memory impairment by altering the cholinergic system in a mouse model. Groups of mice were given ciproxifan (1 or 3 mg/kg, p.o.) for 30 days. Neurotoxicity was induced with four doses of LPS (250 µg/kg, i.p.) from day-22 to day-25 of drug treatment in three groups. Then, mice were subjected to behavioral assessments using tests [elevated plus maze (EPM), novel object recognition (NOR), and Y-maze]. Also, brain tissues were collected for estimation of cholinergic transmission [acetylcholine (ACh) and acetylcholinesterase (AChE) levels]. Ciproxifan could rescue the memory impairment caused by LPS by shortening the transfer latency in the EPM test, increasing the time spent to explore a novel object and increasing the Discrimination Index in the NOR test and increasing the number of entries to the novel arm and duration of time spent in the novel arm in the Y-maze test. Ciproxifan increased the levels of ACh by decreasing AChE activity in LPS-treated mice. Ciproxifan treatment can improve memory impairment in mice by increasing ACh levels and decreasing AChE levels.


A proteomics approach towards understanding blast fungus infection of rice grown under different levels of nitrogen fertilization.
Proteins extracted from leaf blades of rice plants infected with blast fungus, Magnaporthe grisea, were separated by two-dimensional polyacrylamide gel electrophoresis. The separated proteins were electroblotted onto a polyvinylidene difluoride membrane, and 63 proteins were analyzed by a gas-phase protein sequencer. The N-terminal amino acid sequences of 33 out of 63 proteins were determined in this manner. N-terminal regions of the remaining proteins could not be sequenced. The internal amino acid sequences of 12 proteins were determined by sequence analysis of peptides obtained by the Cleveland peptide mapping method. The amino acid sequences were compared with those of known plant and animal protein sequences to understand the nature of these proteins. As expected, leaf blades revealed predominantly the presence of photosynthetic proteins. Using this experimental approach named as proteome analysis, the functional proteins during blast fungus infection of rice with different levels of nitrogen nutrient were analyzed. Twelve proteins which appeared to change with different levels of nitrogen nutrient were identified. It was revealed that the level of ribulose-1,5-bisphosphate carboxylase/oxygenase was increased by top-dressing with nitrogen nutrient. Additionally, the pathogenesis related protein were observed following blast fungus infection using immunoblot analysis. It was conjectured that these proteins might be involved in incompatible interaction in rice plants following blast fungus infection. The information obtained on the amino acid sequences and antibodies interaction is expected to be helpful in predicting the function of these proteins.


The magnitude of adhesion-related problems.
Adhesions perhaps should be considered to be the most frequent complication of abdominopelvic surgery. The incidence is well documented but the burden to the cost of healthcare is not given the recognition it deserves. For any other disease or operation, with a recognized complication with such a high incidence, a prophylactic therapy or preventative strategy would be recommended if not mandatory. Adhesions occur in over 95% of all abdominal operations and can account for up to 6% of all readmissions. The problem affects all ages and exists for the life of the patient.


[Treatment of hypertension with device-guided breathing exercise].
Hypertension has been documented as a major risk factor for cardiovascular morbidity and mortality and lowering blood pressure (BP) can reduce this risk. Life style modifications such--as physical exercise, salt restriction and weight reduction can lower BP. Recently, a number of studies showed that device-guided breathing exercise, which lowers the respiration rate and modifies respiratory patterns, can also lower BP. Deep and slow breathing increase baroreflex sensitivity and heart rate variability, improve small vessels blood flow, and decrease peripheral resistance, thereby leading to BP reduction. Several studies including 268 hypertensive patients showed that 15 minutes of daily breathing exercise lowered BP within 8 weeks by 12.1/6.1 mmHg as compared to 7.6q3.4 mmHg in the control group. Most patients complied with the treatment. These results suggest that device guided breathing exercise can be used to lower BP.


Intelligent querying and exploration of multiple time-oriented medical records.
Querying and analyzing multiple time-oriented patient data is a key task during medical research, clinical trials or the assessment of the quality of therapy. In this paper, we present several aspects of the VISITORS system, which includes knowledge-based tools for graphical querying and exploration of multiple longitudinal patient records. We focus on the syntax and semantics of the knowledge-based aggregation query language for multiple time-oriented patient records, and on the graphical query-construction interface. The query language assumes an underlying computational method for deriving meaningful abstractions from single and multiple patient records, such as we had previously developed. The aggregation query language enables population querying using an expressive set of constraints. By using our underlying temporal mediator architecture, the time needed to answer typical temporal-abstraction aggregation queries on databases of 1000 to 10,000 patients was reasonable.


Gonadotropin-releasing hormone stimulates phosphatidylinositol labeling and prostaglandin E production in Leydig cells.
The direct effects of gonadotropin releasing hormone (GnRH) upon testicular function include a rapid (integral of 20 min) receptor-mediated increase in phosphatidylinositol (PI) turnover. Incubation of rat interstitial cells with the super-agonist [D-Ala6]desGly10-GnRH N ethylamide (GnRHa) resulted in increased incorporation of [32P]Pi into PI (2-fold at 20 min). The effect on phospholipid turnover was followed by increased prostaglandin E (PGE) and testosterone production (3 h; with ED50 values of 0.5 and 0.75 nM respectively). It is concluded that increased PI turnover and PGE production might be involved in mediating the direct testicular effects of GnRH and its agonists.


Ambulation and physical function after eccentric resistance training in adults with incomplete spinal cord injury: A feasibility study.
Background: Strengthening the lower extremities has shown to positively influence walking mechanics in those with neurological deficiencies. Eccentric resistance training (ERT) is a potent stimulus for the development of muscular strength with low metabolic demand. Thereby, ERT may benefit those with incomplete spinal cord injuries (iSCI) seeking to improve ambulatory capacity. Design: This study was aimed to determine the effect of ERT on walking speed, mobility, independence, and at home function following iSCI. Methods: Individuals with longstanding iSCI trained twice a week for 12 weeks on an eccentrically biased recumbent stepper. Outcome measures: Walking speed (10 meter walk test; 10MWT), mobility (timed up and go), independence (Walking Index for Spinal Cord Injury; WISCI), and at home function (Spinal Cord Independence Measure; SCIM) were assessed at baseline, after 6 weeks, and after 12 weeks of ERT. Results: There were improvements in walking mobility (158.36 + 165.84 seconds to 56.31 + 42.42 seconds, P = .034, d = 0.62), speed (0.34 + 0.42 m/s to 0.43 + 0.50 m/s, P = .005, d = .23), and independence (8 + 7 to 13 + 7, P = .004, d = .73) after 12 weeks of ERT. At home function remained unchanged (22 + 10 to 24 + 10, P = .10, d = .12). Conclusions: Improving lower extremity strength translated to walking performance and independence in those with iSCI. Additionally, ERT may diminish therapist burden in programs designed to improve ambulatory capacity or strength in those with iSCI.


Nanoparticle assisted photothermal deformation of individual neuronal organelles and cells.
Stimulation of the localized surface plasmon of metallic nanoparticles has been shown to be an effective mechanism to induce photothermal damage in biological tissues. However, few studies have focused on single cell or subcellular ablation. Our results show that, upon incubation, gold nanostars are internalized by neurons of acute mouse cerebellar brain slices, clustering inside or close to the nucleus. By stimulating the nanostars' surface plasmon using a femtosecond laser, we show deformation of single nuclei and single cells. Given its precision and extremely localized effect, this is a promising technique for photothermal therapy in areas sensitive to collateral thermal damage such as the nervous system.


Recurrent cholangiocarcinoma in the biliary tree after liver transplantation.
Four liver transplant recipients with recurrent cholangiocarcinoma (CCA) within the allograft biliary tree are described. One patient received a transplant for known CCA and three received transplants for end-stage primary sclerosing cholangitis, in which CCA was found within the hepatectomy specimen. All four developed biliary obstruction due to malignant stricture at the bile duct anastomosis 9-15 months after transplantation. Diagnosis of recurrent CCA was made by means of transhepatic brush biopsy in two patients. Recognition that the biliary tract, especially the anastomosis, is a site of recurrence of CCA should facilitate prompt diagnosis by means of transhepatic brush biopsy in patients with biliary obstruction due to stricture. In addition, because of an association between CCA and primary sclerosing cholangitis, preoperative bile duct biopsy should be considered for liver transplantation candidates with the latter condition. Positive biopsy findings may preclude transplantation.


Machine-learning prediction of the formation of atomic gold wires by mechanically controlled break junctions.
One of the challenging issues in the formation of atomic wires in break-junction experiments is the formation of stable monoatomic chains of reasonable length. To address this issue, in this study, we present a combination of unsupervised and supervised machine learning models trained on the experimentally measured conductance traces, with a goal to develop a microscopic understanding. Applying a machine learning model to two independent data sets from two different samples containing 72 000 and 90 000 conductance-displacement traces of single-atomic junctions, respectively, we first obtain the optimum conditions of bias and the stretching rate for the formation of chains of length > 4 Å. A deep learning method is subsequently applied for the classification of individual breaking traces, leading to the identification of trace features related to long-chain formation. Further investigation by ab initio molecular dynamics simulations provides a molecular-level understanding of the problem.


A wearable computing platform for developing cloud-based machine learning models for health monitoring applications.
Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge. In this paper, we present a novel wearable computing platform for unobtrusive collection of labeled datasets and a new paradigm for continuous development, deployment and evaluation of machine learning models to ensure robust model performance as we transition from the lab to home. Using this system, we train activity classification models across two studies and track changes in model performance as we go from constrained to unconstrained settings.


Intracranial metastases in prostate cancer.
In a clinicopathologic review of 126 autopsied cases with prostate cancer, 14 demonstrated intracranial metastases. Only two of nine symptomatic patients were evaluated for suspected central nervous system metastases prior to death, and five asymptomatic patients were incidentally found to have metastases at autopsy. Intracranial metastases in prostate cancer occur in the setting of widespread disease, and tissue pathology may reveal moderately to poorly differentiated tumor (11 of 14 cases).


Molecular dynamics simulations reveal statistics and microscopic mechanisms of water permeation in membrane-embedded artificial water channel nanoconstructs.
Understanding water transport mechanisms at the nanoscale level remains a challenge for theoretical chemical physics. Major advances in chemical synthesis have allowed us to discover new artificial water channels, rivaling with or even surpassing water conductance and selectivity of natural protein channels. In order to interpret experimental features and understand microscopic determinants for performance improvements, numerical approaches based on all-atom molecular dynamics simulations and enhanced sampling methods have been proposed. In this study, we quantify the influence of microscopic observables, such as channel radius and hydrogen bond connectivity, and of meso-scale features, such as the size of self-assembly blocks, on the permeation rate of a self-assembled nanocrystal-like artificial water channel. Although the absolute permeation rate extrapolated from these simulations is overestimated by one order of magnitude compared to the experimental measurement, the detailed analysis of several observed conductive patterns in large assemblies opens new pathways to scalable membranes with enhanced water conductance for the future design.


Association between spoligotype-VNTR types and virulence of Mycobacterium bovis in cattle.
Mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that affects approximately 5% of Argentine cattle. The aim of this research was to study if it is possible to infer the degree of virulence of different M. bovis genotypes based on scorified observations of tuberculosis lesions in cattle. In this study, we performed association analyses between several parameters with tuberculosis lesions: M. bovis genotype, degree of progression of tuberculosis, and animal age. For this purpose, the genotype was determined by spoligotyping and the degree of bovine tuberculosis gross lesion was quantified with a score based on clinical observations (number, size, and location of granulomas along with histopathologic features). This study was performed with naturally infected cattle of slaughterhouses from three provinces in Argentina. A total of 265 M. bovis isolates were obtained from 378 pathological lesion samples and 192 spoligotyping and VNTR (based on ETR sequences) typing patterns were obtained. SB0140 was the most predominant spoligotype, followed by SB0145. The spoligotype with the highest lesion score was SB0273 (median score of 27 ± 4.46), followed by SB0520 (18 ± 5.8). Furthermore, the most common spoligotype, SB0140, had a median score of 11 ± 0.74. Finally, the spoligotype with the lowest score was SB0145 (8 ± 1.0). ETR typing of SB0140, SB0145, SB0273, and SB0520 did not subdivide the lesion scores in those spoligotypes. In conclusion, SB0273 and SB0520 were the spoligotypes with the strongest association with hypervirulence and both spoligotypes were only found in Río Cuarto at the south of Córdoba province. Interestingly, there is no other report of any of these spoligotyes in Latin America.


Detecting ordered small molecule drug aggregates in live macrophages: a multi-parameter microscope image data acquisition and analysis strategy.
Following prolonged administration, certain orally bioavailable but poorly soluble small molecule drugs are prone to precipitate out and form crystal-like drug inclusions (CLDIs) within the cells of living organisms. In this research, we present a quantitative multi-parameter imaging platform for measuring the fluorescence and polarization diattenuation signals of cells harboring intracellular CLDIs. To validate the imaging system, the FDA-approved drug clofazimine (CFZ) was used as a model compound. Our results demonstrated that a quantitative multi-parameter microscopy image analysis platform can be used to study drug sequestering macrophages, and to detect the formation of ordered molecular aggregates formed by poorly soluble small molecule drugs in animals.


Using Virtual Care to Facilitate Direct Hospital Admissions in Outpatients with Worsening COVID-19 Infection.
Recognizing emergency department overcrowding during the COVID-19 pandemic, a pathway to facilitate direct admissions for outpatients with worsening COVID-19 infection was created using the COVID-19 expansion to outpatients (COVIDEO) virtual care program. Outpatients appropriate for direct admission had oxygen saturations consistently <92% without severe respiratory distress. Pulse oximeters were proactively delivered to high-risk patients, and patients contacted the program in the event of worsening symptoms or desaturation persistently <92%. Over a 15-month period, 9,116 outpatients were managed by the program, 164 of whom were hospitalized, and 83 of those hospitalized (50.6%) were directly admitted through this pathway. Of those directly admitted, 10 (12.0%) patients required ICU admission, occurring a median of 4 days from hospital admission. The mortality rate among directly admitted patients was 3.6% (3/83). Implementation of a virtual care program to facilitate direct admissions in outpatients with COVID-19 created a safe, efficient, and patient-centered pathway of care.


Design of Binary-Sequence Zone Plates in High Wavelength Domains.
The design of zone plates is an important topic in many areas of physics, such as optics, X-rays, microwaves or ultrasonics. In this paper, a zone plate design method, which provides high flexibility in the shaping of the focusing profile, is analyzed. This flexibility is achieved through the use of binary sequences that produce zone plates with different properties and applications. It is shown that this binary-sequence method works properly at low wavelengths, but requires a modification term to work accurately in high wavelength domains. This additional term extends this powerful design method to any wavelength. Simulation results show acoustic focusing profiles for Fresnel, Fibonacci and Cantor zone plates operating at a wavelength of 1.5 mm without any distortion.


Thin layer chromatography-ion mobility spectrometry (TLC-IMS).
Ion mobility spectrometry (IMS) is a fast and sensitive analytical method which operates at the atmospheric pressure. To enhance the capability of IMS for the analysis of mixtures, it is often used with preseparation techniques, such as GC or HPLC. Here, we report for the first time the coupling of the thin-layer chromatography and IMS. A variety of coupling schemes were tried that included direct electrospray from the TLC strip tip, indirect electrospray from a needle connected to the TLC strip, introducing the moving solvent into the injection port, and, the simplest way, offline introduction of scratched or cut pieces of strips into the IMS injection port. In this study a special solvent tank was designed and the TLC strip was mounted horizontally where the solvent would flow down. A very small funnel right below the TLC tip collected the solvent and transferred it to a needle via a capillary tubing. Using the TLC-ESI-IMS technique, acceptable separations were achieved for two component mixtures of morphine-papaverine and acridine-papaverine. A special injection port was designed to host the pieces cut off the TLC. The method was successfully used to identify each spot on the TLC by IMS in a few seconds.


Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy.
5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to evaluate the bioavailability of s.c. granisetron. Patients receiving platinum-based chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance. From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration-time curve for 0-12 hours (AUC(0-12h)) and higher levels at 12 hours, with similar values for AUC(0-24h). The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration. Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration might be especially relevant for outpatient management of emesis in cancer patients.


Protonophore properties of hyperforin are essential for its pharmacological activity.
Hyperforin is a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), recommended as a treatment for a range of ailments including mild to moderate depression. Part of its action has been attributed to TRPC6 channel activation. We found that hyperforin induces TRPC6-independent H(+) currents in HEK-293 cells, cortical microglia, chromaffin cells and lipid bilayers. The latter demonstrates that hyperforin itself acts as a protonophore. The protonophore activity of hyperforin causes cytosolic acidification, which strongly depends on the holding potential, and which fuels the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na(+) cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines. In summary the pharmacological actions of the "herbal Prozac" hyperforin are essentially determined by its protonophore properties shown here.


The categories of cutaneous mosaicism: A proposed classification.
Mosaic disorders can most easily be studied in the skin. This article presents a comprehensive overview of the different forms of cutaneous mosaicism. Major categories are genomic versus epigenetic mosaicism and nonsegmental versus segmental mosaicism. The class of nonsegmental mosaics includes single point mosaicism as exemplified by solitary benign or malignant skin tumors; disseminated mosaicism as noted in autosomal dominant tumor syndromes such as neurofibromatosis 1; and patchy mosaicism without midline separation as found in giant melanocytic nevus. The class of segmental mosaics includes segmental manifestation of lethal genes surviving by mosaicism as noted in Proteus syndrome; type 1 segmental mosaicism of autosomal dominant skin disorders reflecting heterozygosity for a postzygotic new mutation; type 2 segmental mosaicism of autosomal dominant skin disorders reflecting loss of heterozygosity that occurred at an early developmental stage in a heterozygous embryo; and isolated or superimposed segmental mosaicism of common polygenic skin disorders such as psoriasis or atopic dermatitis. A particular form of genomic mosaicism is didymosis (twin spotting). Revertant mosaicism is recognizable as one or more areas of healthy skin in patients with epidermolysis bullosa or other serious genodermatoses. The category of epigenetic mosaicism includes several X-linked, male lethal disorders such as incontinentia pigmenti, and the patterns of lyonization as noted in X-linked non-lethal disorders such as hypohidrotic ectodermal dysplasia of the Christ-Siemens-Touraine type. An interesting field of future research will be the concept of epigenetic autosomal mosaicism that may explain some unusual cases of autosomal transmission of linear hypo- or hypermelanosis.


Geometric analysis of light-field position of a multileaf collimator with curved ends.
The purpose of this work was to analyze the difference between the light-field edge and the radiation field edge produced by multileaf collimator (MLC) leaves that are constructed with rounded ends. A formula was derived using three-dimensional geometry predicting the location of the ideal point-source light-field edge relative to the geometric projection of the tip of the rounded leaf end. The theoretical edge of the radiation field for a point source was also calculated along the projection of a chord whose length was one Half-Value Thickness (HVT). Analytic solutions were found for the radiation-field edge and the transmission penumbra. The displacement of the light-field edge relative to the projection of the leaf tip varied from 0 mm for the leaf tip projected onto the central axis to approximately 3.2 mm for the leaf tip projected to 20 cm off the central axis. The light-field edge was always displaced into the unblocked area. The location of the projection of the 1 HVT chord was displaced from the light-field edge by a small and essentially constant distance (approximately 0.3 mm) for all field sizes. The transmission penumbra (80%-20%) was about 1.2 mm for all leaf positions. The calibration of the leaf position must account for the nonlinear relationship between the leaf-tip projection and the light-field (or radiation-field) edge.


Preliminary Report on Histopathology of Odontogenic Keratocyst in Third Dimension: Three-Dimensional Video and Images.
Odontogenic keratocyst (OKC) is a developmental odontogenic cyst of the jaws that causes extensive destruction even before the clinical manifestations are evident. It is a well-known entity among private practitioners as it has a high recurrence rate and requires meticulous treatment planning. Unfortunately, clinicians have less understood its basic histopathology. This article highlights the preliminary attempt of an author in designing third dimension of histopathological aspect of OKC so that it is easily understood by oral pathologists, general pathologists, nonpathologists, students, and even patients too. Preliminary three-dimensional (3D) images and videos on histopathological aspect of OKC were designed by the author using 3DMax (Autodesk Media and Entertainment) and Adobe Premiere Pro 5.5 software which is a video editing software (Adobe Systems) based on two-dimensional descriptions mentioned in the literature. Internal cellular architecture of OKC was created in a lifelike manner through 3D animation video and images. Histopathological aspect of all oral lesions should be explained in third dimension too.


[Transmissivity of drug resistance in Salmonella].
The experiments showed that among 110 Salmonella strains resistant to 1 or more antibiotics 54.5 per cent of the cultures transfered their resistance to E. coli when grown in vitro. The frequency of the transmissive drug resistance in Salmonella was directly proportional to the number of r-determinants in R-factor. The cultures resistant to ampicillin and kanamycin proved to be the most competent donors.


Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells.
Aberrant expression of the protease-activated receptor (PAR)-1 has been associated with tumour progression. Indeed, PAR-1 expression correlates with tumour invasiveness, as well as with cancer cell survival. As the tumour microenvironment is characterised by a low oxygen tension, we decided to investigate the role of PAR-1 in cancer cells exposed to a hypoxic microenvironment. In this study we show that hypoxia enhances PAR-1 expression in MDAMB231 breast cancer cells. We next provided evidence for a novel role of PAR-1 in protecting hypoxic breast cancer against cell death, since inhibition of PAR-1 by RNA interference resulted in a decreased cell survival. Finally, we found that treatment of hypoxic MDAMB231 cells with the specific PAR-1 agonist peptide (TRAP) resulted in a significant increase of cell survival and migration. The overall results identify for the first time a functional role for PAR-1 in the cellular responses of breast cancer to a hypoxic microenvironment.


The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell protection.
Microglia of the central nervous system serve a variety of functions that may ultimately lead to the development or detriment of neighboring neuronal and vascular cells. These scavengers of the nervous system have been associated with a variety of neurodegenerative disorders, but the toxic potential of microglia is equally balanced by the protective nature of these cells to exclude foreign microorganisms and promote new tissue proliferation and reorganization. To this extent, our work outlines a series of endogenous microglial cellular pathways that can constitute protection for microglia against during oxygen-glucose deprivation (OGD). We demonstrate in both primary microglia and the microglial cell line EOC 2 that endogenous microglial protection against OGD relies upon the activation and expression of the phosphatidylinositol 3-kinase pathways of mammalian target of rapamycin (mTOR) and protein kinase B (Akt1), since pharmacological inhibition of mTOR or Akt1 as well as the gene silencing of Akt1 protein expression leads to significantly increased microglial apoptotic cell injury, DNA fragmentation, and membrane phosphatidylserine exposure. The mTOR pathway may offer endogenous protection through mechanisms that do not entirely rely upon inhibition of glycogen synthase kinase-3beta (GSK-3beta) activity while Akt1 appears to converge upon the necessary blockade of GSK-3beta. Closely aligned to these endogenous protective mechanisms is the subcellular presence and nuclear translocation of nuclear factor-kappaB p65 (NF-kappaB p65), since microglial cell injury is significantly increased during the gene silencing of NF-kappaB p65. Elucidating the underlying pathways that can afford endogenous protection and maintain functional integrity of microglia should offer new prospects for the treatment of a broad range of nervous system disorders.


Properties of nearly one-electron molecules. I. An iterative Green function approach to calculating the reaction matrix.
An ab initio R-matrix method for determining the molecular reaction matrix of scattering theory is introduced. The method makes use of a principal-value Green function to compute the collision channel wave functions for the scattered electron, in combination with the Kohn variational scheme for the evaluation of R-matrix eigenvalues on a spherical boundary surface at short range. This technique permits the size of the bounded volume in the variational calculation to be reduced, making the computations fast and efficient. The reaction matrix is determined in a form that minimizes its energy dependence. Thus the procedure does not require modification or an increase in the computational effort to study the electronic structure and dynamics in Rydberg molecules with extremely polar ion cores. The analysis is specialized to examine the bound-state and free-electron scattering properties of nearly one-electron molecular systems, which are characterized by a Rydberg/scattering electron incident on a closed-shell ion core. However, it is shown that the treatment is compatible with all-electron/ab initio representations of open-shell and nonlinear polyatomic ion cores, emphasizing its generality. The introduced approach is used to calculate the electronic spectrum of the calcium monofluoride molecule, which has the extremely polar (Ca+2F-)+e- closed-shell ion-core configuration. The calculation utilizes an effective single-electron potential determined by M. Arif, C. Jungen, and A. L. Roche [J. Chem. Phys. 106, 4102 (1997)] previously. Close agreement with experimental data is obtained. The results demonstrate the practical utility of this method as a viable alternative to the standard variational approaches.


Angiotensin II and IV stimulate expression and release of plasminogen activator inhibitor-1 in cultured human coronary artery endothelial cells.
There is increasing evidence that angiotensin II influences thrombogenesis by regulating the expression of plasminogen activator inhibitor-1 (PAI-1). In this study, the effects of angiotensin II and its receptors on the expression and release of PAI-1 and tissue-type plasminogen activator (t-PA) were examined in human coronary artery endothelial cells (HCAECs). As control, cells were treated with angiotensin IV. HCAECs incubated with angiotensin II increased the expression of PAI-1 mRNA in a concentration (10-9-10-5 M)- and time (6-24 h)-dependent manner. PAI-1 protein release was also increased in the culture medium of HCAECs treated with angiotensin II. The effects of angiotensin II (10-6 M) were blocked completely by the AT1 receptor blocker losartan (10-6 M) but not by the AT2 receptor blocker PD123319 (10-6 M). Angiotensin II pretreatment also slightly, but significantly, increased t-PA mRNA expression. This effect of angiotensin II on t-PA mRNA was blocked by losartan but not by PD123319. HCAECS treated with angiotensin II revealed large amounts of the lipid peroxidation product, malonaldehyde (MDA). The effects of angiotensin II on PAI-1 expression and MDA release were blocked by pretreatment of cells with alpha-tocopherol (10-5 M). In control experiments, treatment of HCAECs with angiotensin IV markedly increased PAI-1 mRNA expression and protein release. This effect of angiotensin IV was blocked by the AT4 receptor blocker divalinal (10-6 M). These observations indicate that AT1 receptor activation plays an important role in the stimulation of PAI-1 expression and release in response to angiotensin II. Upregulation of t-PA gene may reflect autoregulation in response to PAI-1 release. Angiotensin II-mediated activation of oxidation pathways may relate to uupregulation of PAI-1. This study also confirms that angiotensin IV upregulates PAI-1 expression in HCAECs.


Infra-cranial radiographic comparison for human identification: A study of analyst expertise.
Radiographic comparison for identification is widely utilized. However, these methods are qualitative and subject to analyst ability to correctly read and interpret radiographs. With regards to infra-cranial radiographs, few studies have been conducted to explore the role of practitioner expertize on correct classification rates (CCRs). Here, we undertake two such studies using forensic anthropologists [American Board of Forensic Anthropology (ABFA) certified, practicing but not board-certified anthropologists, and chest radiograph comparison (CXR) anthropologists trained via the Defense POW/MIA Accounting Agency CXR competency training program] and compare their results to novices. To ensure participants only referred to the same skeletal morphology, we cropped radiographs to single bones. An array of four simulated antemortem radiographs was presented to each assessor with each postmortem radiograph. Assessors evaluated arrays for a correct match, which was always present, yielding a 25% rate for random correct selections. Study 1 used anteroposterior C7, posteroanterior second metacarpal, and lateral calcaneus radiographs (three arrays each for nine arrays total), which yielded 86, 81, 69, and 68% mean CCRs for CXR experts, ABFA anthropologists, non-ABFA anthropologists and novices, respectively. Study 2 used anteroposterior C7 and left clavicles (three arrays each for six arrays total), yielding mean CCRs of 100, 96, and 84% for CXR experts, ABFA anthropologists and novices, respectively. As reflected by the CCRs, expertise is clearly a factor for radiographic comparisons, evident not just between novices and anthropologists, but also between anthropologists. We recommend all radiographic comparison analysts be subject to competency/proficiency tests prior to their engagement for forensic casework.


Latent mobility of osteoporotic vertebral compression fractures.
To describe the property of latent mobility in osteoporotic vertebral compression fractures (VCFs) and discuss its clinical significance. This was a retrospective case series of 14 patients with 14 painful osteoporotic VCFs who were comfortably confined to the supine position overnight for the purpose of vertebral height restoration. There was sufficient additional vertebral height restoration the following morning to allow percutaneous vertebroplasty (PV) in some patients when this had initially been deemed unsafe or technically impossible. Anterior vertebral height of the index VCF was measured from the preoperative standing lateral, immediate cross-table supine lateral, and postconfinement cross-table supine lateral radiographs as well as the first postoperative standing lateral radiograph. Dynamic mobility was defined as the difference in anterior vertebral height between preoperative standing lateral and immediate cross-table supine lateral radiographs. Latent mobility was defined as difference in anterior vertebral height between immediate cross-table supine lateral and postconfinement cross-table supine lateral radiographs. Postoperative vertebral height restoration was defined as the difference in anterior vertebral height between preoperative and first postoperative standing lateral radiographs. Mean patient age was 81.0 years, and mean fracture age was 83.6 days. Dynamic mobility averaged +4.7 mm (range, -2.1 to +12.6 mm; P = .001). Latent mobility averaged +2.7 mm (range, -1.9 to +15.5; P < .02). The average sum of preoperative dynamic and latent mobility (+7.4 mm; range -1.0 to +17.0; P < .001) was not different from final postoperative vertebral height restoration (P > .4). PV was successfully accomplished in all cases. Latent mobility occurs in some VCFs and contributes to vertebral height restoration. Recognition of latent mobility may permit vertebroplasty in some patients in whom the procedure had otherwise been deemed unsafe. Reports of vertebral height restoration following vertebral augmentation should account for that proportion resulting from dynamic and latent mobility.


Reversal of Lead-Induced Acute Toxicity by Lipoic Acid with Nutritional Supplements in Male Wistar Rats.
Lead (Pb) is a pleiotropic toxicant. The potential role of oxidative stress injury that is associated with Pb poisoning suggests that antioxidants may enhance the efficacy of treatment designed to mitigate Pb-induced toxicity. The aim of this study is to investigate the comparative ameliorative potential of lipoic acid (LA) alone or in combination with calcium (Ca) and zinc (Zn). Pb acetate (50 mg/kg, intraperitoneally) was administered for 3 d. After 24 h of the last toxicant dose, LA (100 mg/kg, orally [po]) alone or in conjuction with Ca (50 mg/kg, po) and Zn (10 mg/kg, po) was administered for 3 d. Significant alterations in the concentration of urea, uric acid, triglycerides, cholesterol, aspartate amino transferase, alanine amino transferase, lipid peroxidation, and reduced glutathione as well as alterations in enzyme activity of δ-aminolevulinic acid (ALA) dehydratase were observed following acute Pb exposure. These findings were also supported by elevated mean DNA damage and Pb body burden in blood and soft tissues compared to controls (p ≤ 0.05). Three d posttreatment with LA along with Zn and Ca could significantly restore the biochemical parameters and Pb body burden to near-normal status through antioxidant activity or by preventing bioaccumulation of Pb within the blood and tissues of experimental rats.