Short Stop provides an essential link between F-actin and microtubules during axon extension.
Coordination of F-actin and microtubule dynamics is important for cellular motility and morphogenesis, but little is known about underlying mechanisms. short stop (shot) encodes an evolutionarily conserved, neuronally expressed family of rod-like proteins required for sensory and motor axon extension in Drosophila melanogaster. We identify Shot isoforms that contain N-terminal F-actin and C-terminal microtubule-binding domains, and that crosslink F-actin and microtubules in cultured cells. The F-actin- and microtubule-binding domains of Shot are required in the same molecule for axon extension, though the length of the connecting rod domain can be dramatically reduced without affecting activity. Shot therefore functions as a cytoskeletal crosslinker in axon extension, rather than mediating independent interactions with F-actin and microtubules. A Ca(2+)-binding motif located adjacent to the microtubule-binding domain is also required for axon extension, suggesting that intracellular Ca(2+) release may regulate Shot activity. These results suggest that Shot coordinates regulated interactions between F-actin and microtubules that are crucial for neuronal morphogenesis.


La Sota vaccination may not protect against virus shedding and the lesions of velogenic Newcastle disease in commercial turkeys.
The aim of this project is to study the clinical signs and lesion of velogenic Newcastle disease (vND) in commercial turkeys, and also to find out if La Sota vaccination offered protection against these signs and lesions. The cockerels were included as positive controls. One hundred and twenty turkey poults and cockerels were divided into eight groups as follows: unvaccinated unchallenged turkeys (UUT), unvaccinated challenged turkeys (UCT), vaccinated unchallenged turkeys (VUT), vaccinated challenged turkeys (VCT), and along the same lines, the cockerel groups were UUC, UCC, VUC and vaccinated challenged cockerels (VCC). Vaccination was at 3 weeks of age while challenge was at 6 weeks of age. The unvaccinated turkeys and cockerels (UCT and UCC) showed different degrees of depression, diarrhoea and later paralysis at challenge. Total mortality was 100% in cockerels within 6 days, but 60% in turkeys. Similar but milder clinical signs were found in the VCC with a total mortality of 13.3%. The VCT showed mild drop in feed and water consumption, and no mortality. All the challenged groups had significant (p < 0.05) loss of weight when compared with their controls. Necropsy showed that while the UCC had severe proventricular haemorrhages, intestinal and caecal tonsil ulcers, the UCT had no digestive tract lesion. There was severe atrophy of the lymphoid organs in all the challenged groups. Histopathological sections of the bursa, spleen and thymus in all the challenged groups with special emphasis on the vaccinated and unvaccinated turkeys with mortalities of 0 and 60%, respectively, had very severe necrosis and depletion of the lymphoid tissue. Virus was isolated from the cloacal swabs. The haemagglutination inhibition antibodies were significantly higher (p < 0.05) in the challenged groups than the unchallenged. The above observations in the intestinal tracts of UCT are of diagnostic significance while the gross and microscopic lesions in the UCT and VCT show that La Sota vaccination may not protect turkeys against the destruction of the lymphoid organs by vND as earlier reported in chickens. This may lead to immunosuppression and production problems in areas where vND is enzootic.


The immunocytochemical preservation of IgE and mast cells of the rat.
The localisation of IgE to mast cells of rats infested with Nippostrongylus brasiliensis has been studied in an attempt to find a fixation procedure which will best preserve (a) the antigenicity of IgE for immunocytochemical demonstration, and (b) the histochemical staining properties of mast cells. A fixative comprising Carnoy's fluid and picric acid (CPA) best fulfilled these criteria, allowing localisation of IgE to both the plasma membrane and cytoplasm of mucosal mast cells of rat small intestine, but only to the plasma membrane of connective tissue mast cells of rat tongue. Formaldehyde-containing fixatives prevented labelling of IgE in the cytoplasm of mucosal mast cells.


Tai Chi for heart attack survivors: qualitative insights.
Cardiac rehabilitation (CR) programmes are standard of care for patients following a coronary event. While such exercise-based secondary prevention programme do offer benefits, they are used by less than 30% of eligible patients and attrition within these programmes is high. This project is a nested qualitative assessment of a pilot programme considering Tai Chi (TC) as an alternative to CR. We hypothesised that TC may overcome several key barriers to CR. A semistructured focus group agenda was used to assess three key domains of feasibility: (1) patients' experiences, (2) reasons/barriers for not having attended CR and (3) any improvements in physical activity and other secondary outcomes (quality of life, weight, sleep). A thematic analysis was used to better understand the key concepts. This high-risk group of patients reported that they enjoyed TC exercise, and felt confident and safe doing it. TC practice was reported to support other types of physical activity allowing for a generalisation of positive effects. This analysis is consistent with published reports of TC practice improving mood and psychological well-being. Qualitative methods allowed us to find emergent experiential reports of behaviour change factors found in established behaviour change theories.


Diagnosing nasopharyngeal cancer.
When nasopharyngeal carcinoma is suspected clinically, an adequate tissue sample should be taken at the patient's first visit. Should the initial tissue sample be nondiagnostic, depending on the index of suspicion in the individual case, the process may be repeated under either local or general anesthesia. It is important that a detailed examination of the nasopharynx be undertaken in the outpatient setting. Biopsy should be performed accurately under direct visualization. Large biopsy forceps are essential to obtain an adequate tissue sample. Biopsy under local anesthesia is safe, easy to perform, well tolerated by the patient, and should be undertaken in the outpatient clinic. This direct diagnostic approach achieves a rapid diagnosis in patients with nasopharyngeal carcinoma.


Cytophotometric DNA-analysis of bone-tumors. A new method for preparing formalin-fixed tissue and the regarding of DNA-malignancy grade and its prognostic value.
78 benign and malign, formalin-fixed bone or bone-associated tumors of different origin were prepared for image-cytophotometric measuring with a new method of preparing. The DNA-content of the tumors and the so resulting malignancy-grade were determined and compared with the corresponding measurements of unprepared fresh tumors respectively paraffin-embedded tissue sections. Regarding the comparison of the fresh material with the formalin-fixed material, no significant difference (p < or = 0.01) of the data could be found. There was also no significant difference (p < or = 0.01) concerning the comparison of the data obtained from the formalin-fixed material and the data from the tissue sections. The criterium aneuploidy showed a sensitivity of 86% and a specificity of 100% in regards to identifying a malignant tumor, irrespective of the preparation method. A strong correlation could be found (p < 0.001) between the DNA-malignancy grade and the survival rate of the patients.


Tumor antigen occurs in N-glycan of royal jelly glycoproteins: honeybee cells synthesize T-antigen unit in N-glycan moiety.
In our previous paper (Kimura, Y., et al., Biosci. Biotechnol. Biochem., 67, 1852-1856, 2003), we found that a complex type N-glycans containing beta1-3 galactose residue occurs on royal jelly glycoproteins. During structural analysis of minor components of royal jelly N-glycans, we found complex type N-glycans bearing both galactose and N-acetylgalactosamine residues. Detailed structural analysis of pyridylaminated oligosaccharide revealed that the newly found N-glycan had a complex type structure harboring a tumor marker (T-antigen) unit: Galbeta1-3GalNAcbeta1-4GlcNAcbeta1-2Manalpha1-6 (Galbeta1-3GalNAcbeta1-4GlcNAcbeta1-2Manalpha1-3) Manbeta1-4GlcNAcbeta1-4GlcNAc. To our knowledge, this may be the first report of the presence of the T-antigen unit in the N-glycan moiety of eucaryotic glycoproteins.


Altered postnatal expression of insulin-like growth factor-I (IGF-I) and type X collagen preceding the Perthes' disease-like lesion of a rat model.
The spontaneously hypertensive rat (SHR) is a widely used animal model for the study of hypertension. It also exhibits an osteonecrosis of the femoral epiphysis that resembles the clinical features of Perthes' disease in humans. In this rat model, occlusion of the epiphyseal vessels occurs as a result of a breakdown of the mechanically vulnerable epiphysis. The postnatal development of the epiphysis recapitulates the serial events of the endochondral ossification (i.e., cartilage formation), chondrocyte hypertrophy, cartilage mineralization, vascularization, and introduction of osteoblasts that form the secondary ossification center within the epiphysis. In the present study, a detailed radiographic and histological analysis demonstrates that the osteonecrosis is preceded by a disturbance of the cartilage mineralization and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal development of the femoral epiphysis occurs much earlier than manifestation of the osteonecrosis. They lead us to a hypothesis that yet-unclarified transitional events between the cartilage hypertrophy and the cartilage mineralization may be affected in SHRs. Type X collagen is a developmentally regulated matrix molecule that is implicated in the mineralization of the hypertrophied chondrocytes. We show that the expression of type X collagen during epiphyseal ossification is delayed in SHRs (vs. normal controls), suggesting disturbed growth and/or differentiation of the epiphyseal chondrocytes. Postnatal growth and differentiation of the chondrocytes at least partly depend on insulin-like growth factor-I (IGF-I), which is produced by the chondrocytes in response to the pituitary growth hormone and stimulates cartilage growth in situ. The present study demonstrates an altered IGF-I expression during early postnatal life in SHRs and suggests that the altered IGF-I expression as well as the following delay in upregulation of type X collagen may cause the mechanical vulnerability of the femoral epiphysis in SHRs.


Construction of yellow fever/St. Louis encephalitis chimeric virus and the use of chimeras as a diagnostic tool.
St. Louis encephalitis (SLE) and West Nile (WN) flaviviruses are genetically closely related and cocirculate in the United States. Virus neutralization tests provide the most specific means for serodiagnosis of infections with these viruses. However, use of wild-type SLE and WN viral strains for laboratory testing is constrained by the biocontainment requirements. We constructed two highly attenuated yellow fever (YF) virus chimeras that contain the premembrane-envelope (prM-E) protein genes from the virulent MSI-7 (isolated in the United States) or the naturally attenuated CorAn9124 (Argentina) SLE strains. The YF/SLE (CorAn version) virus and the previously constructed YF/WN chimera were shown to specifically distinguish between confirmed human SLE and WN cases in a virus neutralization test using patient sera. These chimeras have the potential for use as diagnostic reagents and vaccines against SLE and WN.


Isolation and characterization of the tandemly repeated U6 genes from the sea urchin Strongylocentrotus purpuratus.
The tandemly repeated U6 genes were isolated from the sea urchin Strongylocentrotus purpuratus. Each 1.8 kb repeat unit contains a single U6 RNA sequence. There are no sequence similarities between the U6 promoter and other sea urchin snRNA genes, other than a long polypyrimidine tract 3' of the U6 sequence.


Activation of enzymes by calmodulins containing intramolecular cross-links.
We have reacted calmodulins containing cysteines substituted at positions 3 and 146 or 5 and 146 with bismaleimidohexane (BMH) to generate intramolecularly cross-linked proteins termed BMHCM or BMHCM1, respectively. Reactions were also performed with N-ethylmaleimide (NEM) in place of BMH to generate corresponding S-ethylsuccinimidylated proteins termed NEMCM or NEMCM1. The abilities of these proteins to activate plant NAD kinase, erythrocyte Ca(2+)-ATPase and bovine brain calcineurin activities were assessed. The BMH- or NEM-reacted proteins activate calcineurin activity as does control calmodulin. Kact values for Ca(2+)-ATPase activation by BMHCM and BMHCM1 are increased 10-fold relative to the control value, with no corresponding change in Vmax values. Activation of this enzyme by NEMCM or NEMCM1 is not different from the control. In NAD kinase activation experiments BMHCM and BMHCM1 are associated with a 10 to 20-fold increase in Kact values and a 60-75% reduction in Vmax values relative to the control. NEMCM1 is not associated with any apparent changes in NAD kinase activation, however, NEMCM is associated with a 10-fold increase in the Kact value. NEM-reacted calmodulin containing a cysteine only at position 3 is not associated with an increased Kact value, implying that this change is due to interactions between S-(ethylsuccinimido)cysteines at positions 3 and 146. In conclusion, cross-linking and associated distortions in the structure of calmodulin appear to have little or no effect on activation of calcineurin enzyme activity. However, bending in the central helix and/or steric restrictions associated with cross-linking increase significantly the Kact value for Ca(2+)-ATPase and NAD kinase activation, and dramatically reduce maximal activation of NAD kinase activity.


Role of the immune system in cardiac tissue damage and repair following myocardial infarction.
The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.


Nodular nongranulomatous vasculitis of the lung detected by 18F-FDG PET/CT.
We report a case of a nodular nongranulomatous vasculitis of the lung detected by (18)F-FDG PET/CT. A 51-year-old woman with fever of unknown origin underwent (18)F-FDG PET/CT, which showed multiple and bilateral pulmonary nodules at CT scan with increased radiopharmaceutical uptake in the largest one (20 mm in diameter). On the basis of the PET/CT findings, the patient was referred for excisional biopsy of the largest pulmonary nodules suspicious for neoplastic disease. Histological examination demonstrated the presence of an obliterative vasculitis with interstitial pulmonary perivascular inflammation.


[Histocytological correlation in fine needle aspiration biopsy of the thyroid gland].
To correlate cytological diagnosis with the anatomicopathological ones to assess the accuracy of cytological examination as a diagnostic test. The results of 328 cytological diagnoses were compared with the corresponding anatomicopathological results from surgical specimens. In all thyroid diseases the accuracy of the method was above 95%. Among the more frequent diseases, the sensitivity of the test was 98%, 69%, 81%, 85% and 89%, respectively for nodular colloid goiter, follicular neoplasms, Hashimoto's thyroiditis, papillary carcinoma and Hürthle-cell neoplasia; in all of them the test specificity was at least 89%. Based on these results and owing to its relative simplicity, this study also documents the FNAB usefulness as a diagnostic method for thyroid diseases.


SIX DECADES OF THE PULA NEUROPSYCHIATRIC MEETINGS--FROM NEUROPSYCHIATRY TO BORDERLANDS OF NEUROLOGY AND PSYCHIATRY BRAIN AND MIND.
In 2010, the International Neuropsychiatric Pula Symposia, from 2005 Congresses (INPS/INPC), founded in 1961 by Zagreb and Graz University Neuropsychiatry Departments, celebrated their 50th anniversary of successful development. The co-author of the paper, Bosko Barac, witnessed their growth from 1966, collaborating in their organization from 1974 with the first Secretary General Gerald Grinschgl; elected for his successor after his unexpected death in 1985, he was leading the Kuratorium (Scientific Board) as Secretary General for 23 years, collaborating in this period with his Austrian partner and friend Helmut Lechner. In 2007, Barac handed over this responsible function to the co-author Vida Demarin. Starting when neuropsychiatry was a unique discipline, the INPC followed the processes of emancipation of neurology and psychiatry and their evolution to independent disciplines with new subspecialties. These respectable conferences greatly surpassed the significance of the two disciplines, neurology and psychiatry, granting collaboration of borderland medical and non-medical disciplines, connecting experts from the region, European countries and the world. Inaugurated in 'cold-war' times, in their first phase they enabled to make professional and human contacts between scientists from the two divided 'blocs' thanks to the 'non-aligned' position of the then Yugoslavia, fostering the ideas of mutual understanding and collaboration. On the other hand, the scientific development of the meetings took in the center of their study fields connecting the two disciplines, giving a quite unique quality to these meetings. For many years, the meetings cherished specific neurologic and psychiatric topics, at the same time planning increasing important topics of the 'borderland areas' in their programs. For the important achievements, they earned the title of the Pula School of Science and Humanism, promoting interdisciplinary scientific collaboration important for humanistic goals of medicine. Medicine, as science and practice, although founded on biological grounds, is primarily a human activity serving to individual man and the whole human race. Modern neurology and psychiatry are no longer restricted to diagnosing and curing brain and nerves or psychiatric disorders, and are nowadays important as a science of human mind and discipline caring about the human brain, the complex organ of each individual man, collective human consciousness and our mental life. Such atmosphere contributed to the fall of the totalitarian, narrow-minded political, ideological or nationalistic thinking, aiming to tolerance and humane democratic developments in the united Europe and the preparation for peaceful living of various nations, races, religions and viewpoints in the 21st century.


Analysis of oak tannins by liquid chromatography-electrospray ionisation mass spectrometry.
Extractable tannins were analysed by liquid chromatography-electrospray ionisation mass spectrometry in two oak species, North American white oak (Quercus alba) and European red oak (Quercus robur). They mainly included various glucose gallic and ellagic acid esters. The structures were partially determined, and they included grandinin/roburin E, castalagin/vescalagin, gallic acid, valoneic acid bilactone, monogalloyl glucose, digalloyl glucose, trigalloyl glucose, ellagic acid rhamnose, quercitrin and ellagic acid.


Step counts of 10- to 11-year-old children by ethnicity and metropolitan status.
The purpose of this study was to conduct a secondary analysis by combining 2 pedometer data sets to describe and analyze pedometer-determined steps/day of children by ethnicity and metropolitan status. Participants were 582 children (309 girls, 273 boys; 53% Hispanic, 26% Caucasian, 21% African American) age 10 to 11 years (M = 10.37 +/- 0.48) attending 1 of 10 schools located in urban, suburban, and rural settings. Participants wore a research grade pedometer for at least 3 week/school days. Mean steps/day were analyzed by gender, ethnicity, and metropolitan status. Statistical analyses indicated 1) boys (12,853 +/- 3831; P < .001) obtained significantly more steps/day than girls (10,409 +/- 3136); 2) African American (10,709 +/- 3386; P < .05) children accumulated significantly less steps/day than Hispanic (11,845 +/- 3901) and Caucasian (11,668 +/- 3369) children; and 3) urban (10,856 +/- 3706; P < .05) children obtained significantly less steps/day than suburban (12,297 +/- 3616) and rural (11,934 +/- 3374) children. Findings support self-report data demonstrating reduced physical activity among African American children and youth, especially girls, and among children and youth living in urban areas. Possible reasons for these discrepancies are explored.


Diurnal intraocular pressure and blood pressure with two dosing regimens of brimonidine in normal tension glaucoma.
To compare the effects of 2 dosing regimens of brimonidine tartrate 0.2% on diurnal intraocular pressure (IOP) and systemic hemodynamics in patients with normal-tension glaucoma (NTG). Twenty NTG patients were enrolled and randomized to receive either brimonidine twice daily (BID) for 4 weeks followed by brimonidine 3 times daily (TID) for another 4 weeks, or in reverse order. Diurnal variations of IOP and ocular perfusion pressure (OPP), as well as the 24-hour ambulatory blood pressure (BP) and pulse rate, were evaluated at baseline and after treatment. Baseline and post-treatment data were compared using a paired Student's t test, and treatment effects were compared between regimens using a crossover-designed analysis of variance. Both regimens decreased the mean (p < 0.001) and minimum (p < 0.001) diurnal IOP, and only the TID regimen decreased the maximum IOP with a marginal significance (p = 0.049). The TID regimen decreased the maximum OPP (p = 0.009) while the BID regimen caused no changes in OPP. No significant difference in IOP or OPP was noted between regimens at each time point. Neither regimen caused changes in BP or pulse rate as assessed using the 24-hour ambulatory monitoring device. The TID regimen of brimonidine produces similar reductions in diurnal IOP for NTG patients as the BID regimen, and it alone decreases the maximum OPP. Neither of the 2 regimens causes exaggerated nocturnal reduction of BP.


Subarachnoid hemorrhage as complication of phenylephrine injection for the treatment of ischemic priapism in a sickle cell disease patient.
Ischemic priapism (IP) is a urologic condition, which necessitates prompt management. Intracavernosal injection of phenylephrine is a usual treatment modality utilized for the management of these patients. Aim. We present a case of subarachnoid hemorrhage following intracavernosal injection of phenylephrine for IP in a patient with sickle cell disease. We analyzed the degree of subarachnoid hemorrhage in our patient after intracavernosal injection of phenylephrine. The patient had an acute rise in blood pressure during corporal irrigation. This was followed by the onset of severe headache. Computed tomography (CT) scan confirmed the diagnosis of a subarachnoid hemorrhage. Subarachnoid hemorrhage associated with intracavernosal injection of phenylephrine. Result. A 23-year-old African American male with a history of sickle cell disease presented with a painful penile erection. The patient was started on intravenous fluids, oxygen by nasal canula, and analgesic medication. After this, a blood gas was obtained from his left corpora cavernosa. This was followed by normal saline irrigation and injection of phenylephrine. The patient complained of a sudden, severe "terrible headache" immediately following the last injection, and noncontrast CT scan of the head was obtained and a subarachnoid hemorrhage was noted. The patient was admitted for observation and no significant changes were noted. Intracavernosal injection of phenylephrine for the management of IP can be associated with several possible complications. We present our single case complicated with the formation of a subarachnoid hemorrhage. The patient was treated conservatively and had no long-term neurologic sequelae. Davila HH, Parker J, Webster JC, Lockhart JL, and Carrion RE. Subarachnoid hemorrhage as complication of phenylephrine injection for the treatment of ischemic priapism in a sickle cell disease patient.


Human urine kininogenase attenuates balloon-induced intimal hyperplasia in rabbit carotid artery through transforming growth factor β1/Smad2/3 signaling pathway.
Effective treatments against restenosis after percutaneous transluminal angioplasty and stenting are largely lacking. Human tissue kallikrein gene transfer has been shown to be able to attenuate neointima formation induced by balloon catheter. As a tissue kallikrein in vivo, human urinary kininogenase (HUK) is widely used to prevent ischemia-reperfusion injury. However, the effects of HUK on neointima formation have not been explored. We therefore investigated whether HUK could alleviate balloon catheter-induced intimal hyperplasia in rabbits fed with high-fat diets. The effects of HUK on neointima and atherosclerosis formation were analyzed by hematoxylin-eosin staining and immunohistochemical staining in balloon-injured carotid arteries of rabbits. Local inflammatory response was evaluated by detecting the gene expression of tumor necrosis factor α and interleukin 1β with real-time quantitative polymerase chain reaction plus the invasion of macrophages with immunohistochemical staining. Western blotting was employed to investigate the effects of HUK on activities of endothelial nitric oxide synthase (eNOS), transforming growth factor β1 (TGF-β1), and Smad signaling pathway. The long-term effect of HUK on intimal hyperplasia of the injured carotid artery was assessed by angiography. Quantitative image analysis showed that intravenous administration of HUK for 14 days significantly decreased the intimal areas and intima area/media area ratios (day 14, 54% decrease in intimal area and 58% decrease in intima area/media area ratios; day 28, 63% and 85%). Significant decreases were also noted in macrophage foam cell-positive area after 7-day or 14-day administration of HUK (day 7, 69% decrease in intimal area and 78% decrease in media area; day 14, 79% and 60%; day 28, 68% and 44%). Actin staining for smooth muscle cells in neointima at 2 months showed similar results (vascular smooth muscle cell-positive area of neointima, 28.21% ± 5.58% vs 43.78% ± 8.36%; P < .05). Real-time quantitative polymerase chain reaction or Western blot analysis showed that HUK reduced expression of tumor necrosis factor α, interleukin 1β, TGF-β1, and p-Smad2/3 but increased the expression of p-eNOS. Angiography analysis showed that 14-day administration of HUK significantly decreased the degree of stenosis (26.8% ± 7.1% vs 47.9% ± 5.7%; P < .01) at 2 months after balloon injury. Our results indicate that HUK is able to attenuate atherosclerosis formation and to inhibit intimal hyperplasia by downregulating TGF-β1 expression and Smad2/3 phosphorylation, upregulating eNOS activity. HUK may be a potential therapeutic agent to prevent stenosis after vascular injury.


Single center experience with percutaneous and laparoscopic cryoablation of small renal masses.
While partial nephrectomy remains the gold standard for the management of most small renal masses, increasing experience with renal cryoablation has suggested a viable alternative with a favorable morbidity profile and good efficacy. We report intermediate-term oncologic outcomes from a single-center experience with laparoscopic and percutaneous renal cryoablation. We performed a retrospective review of our laparoscopic renal cryoablation (LRC) and percutaneous renal cryoablation (PRC) experience between January 2003 and April 2007. Patients with at least 12 months of follow-up were included in the analysis. Follow-up consisted of imaging and laboratory studies at regular intervals. Persistent mass enhancement or interval tumor growth was considered a treatment failure. Sixty-six patients (44% women/56% men; 42% African-American/58% Caucasian/other; mean body mass index, 29.7) with 72 tumors underwent either LRC (n = 52) or PRC (n = 20) with a mean follow-up of 30 months (median 25.1 mos; range 13-63 mos). Average patient age was 66.5 years (range 34-82 yrs). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 76% hypertension, 36% hyperlipidemia, 24% chronic kidney disease, 29% diabetes mellitus, 36% tobacco use, and 32% heart disease. RESULTS of pretreatment biopsy were 62% renal-cell carcinoma and 38% benign or nondiagnostic. Overall cancer-specific and cancer-free survival were 100% and 97%, respectively. There were two treatment failures (3.8%) in the LRC group and five primary failures in the PRC group (25%) (P = 0.015), four of which were salvaged with repeated PRC with no evidence of recurrence at 6 to 36 months of follow-up. There has been no significant local or metastatic progression. LRC and PRC achieved good oncologic control with minimal morbidity at a mean follow-up of 30 months in a patient cohort characterized by numerous comorbid conditions. PRC had a significantly higher primary treatment failure rate than LRC, but re-treatment offered salvage oncologic control with no significant complications.


Variation in unit costs of hospitals in the English National Health Service.
In England, the Department of Health places high priority on reducing the variation in unit costs of National Health Service (NHS) hospitals. Efficiency targets are set for hospitals to create incentives for relatively high cost hospitals to reduce their costs and shift performance closer to that of their lower cost counterparts. We examine empirically the dispersion in unit costs to assess the extent of variation in the productivity of hospitals and trends over time. We use econometric panel data techniques on data from 235 NHS acute hospital trusts over a six-year period, 1994/95 to 1999/00, supplemented with information from semi-structured interviews with key individuals in hospitals and purchasing bodies. There appears to have been no reduction in variation during this period. Relative unit costs for individual trusts also appear stable, with little movement from relatively high cost to low cost. Judging from limited quantitative evidence outside health care, the variation in costs between NHS hospitals may be comparatively low. Given all the other aspects of hospital performance that government is seeking to change, reduction in the dispersion of unit costs per se should not be a major policy objective. It is far more important to examine variation in quality-adjusted unit costs.


Golf for the senior player.
In no other sport does the senior player enjoy as much opportunity to participate and compete at various skill levels as in golf. No other sport encourages as much mixed competition. Because of their spending power, equipment and travel packages are often geared to the senior player. Advancing medical technology and specialized instruction effectively combat the physical effects of aging. These and other factors will ensure the continued popularity of the game of golf.


[Evaluation of drug cost reduction resulting from the free supply of investigational drugs].
Excluding all other costs or benefits of participation in clinical trials, the objective of this study was to evaluate and analyse the cost avoidance represented by the free supply of the investigational drug in place of paying for a marketed drug. The cost avoided was defined as money that would most likely have been spent, but not because of inclusion of the patient in the clinical study. Only studies for which a marketed alternative drug was available with a standard dosage have been analysed. The numbers of delivered doses or the treatment durations were tabulated from pharmacy dispensing records for each study, and were used to calculate the medication cost avoided. No marketed alternative drug was available for 10 of 56 clinical studies. In total, in 2000, the cost avoidance was estimated between [symbol: see text] 585,492 and [symbol: see text] 603,674, with a wide variability between studies or between patients (CV: 120-520%). The two disease categories associated with the largest cost avoidance were multiple sclerosis and growth hormone deficiency. The cost avoidance was essentially of benefit to the medical insurance or the patient (98%) and was lower than [symbol: see text] 10,000 for the hospital, because 91% of patients are not hospitalised. So, why are clinical studies involving ambulatory patients performed in hospital? Of the 56 studies analysed, 46 could be shown to be non-innovative, because a marketed alternative drug was available. Few studies appeared to permit free access to treatment with non-reimbursable marketed drugs.


Factors predicting the effectiveness of palliative care in patients with advanced cancer.
The purpose of this study was to assess the factors that predict the effectiveness of palliative care in patients with advanced cancer. Cross-sectional data were collected from 240 patients recruited from three tertiary care hospitals in Bangkok and suburban Thailand aged 18 years or older who were willing to participate; able to speak, read, and write Thai; were not receiving aggressive cancer treatment; and had been diagnosed with advanced-stage cancer. Participants were asked to complete a Personal Information Questionnaire (PIQ), a Palliative Care Assessment Form (PCAF), and the Spiritual Well-Being Scale (SWBS). The significant predictors of the effectiveness of palliative care in patients with advanced cancer were found to be spiritual well-being (p = 0.000) and palliative care strategies: a combination of pharmacological and psychosocial care, mind-body intervention, and spiritual care; physical management; and traditional medicine, herbal treatment, and diet management (p = 0.027). The likelihood of effectiveness for patients whose spiritual well-being and palliative care strategies scores increased by an average of one point increased by factors of 1.058 and 2.271, respectively. These findings suggest that patients who experienced better spiritual well-being and who employed a variety of palliative care strategies also experienced enhanced effectiveness of palliative care.


The ontogeny of independent ingestion in mice: or, why won't infant mice feed?
Unlike infant rats, which show deprivation-related ingestion in several different test situations, infant mice appeared to be relatively unwilling to feed independently of suckling until 12 days of age. We tested mouse pups that were deprived (of food, water, suckling, and maternal care) for 1, 7, or 24 hr in ingestive tests in which a milk diet was spread on the floor of their test container (Experiment 1). Pups at 3, 6, and 9 days of age consumed small amounts of the diet and showed little increase in intake when deprivation was increased. In contrast (and like rat pups of all ages), mouse pups 12 and 15 days of age actively ingested the diet and increased their intake with increased deprivation. Six-day-old mouse pups were similarly unwilling to ingest a 5% sucrose solution, though 12-day-old pups showed deprivation-related intake (Experiment 2). Cellular dehydration (produced by hypertonic saline injection), a potent stimulus for ingestion in infant rats, did not stimulate ingestion in mice younger than 12 days of age (Experiment 3). Finally, when ingestion was tested with diet infusions made through oral cannulas, mouse pups at 6 and 9 days of age showed only a slight increase in intake with increased deprivation. However, by 12 days of age, pups' ingestion increased markedly with deprivation (Experiment 4). Thus, mouse pups seem to be very different from rat pups with respect to the early existence of ingestive systems. The neural substrates for the ingestive responses that subserve independent ingestion are only minimally present in infant mice or are somehow inhibited.


Estimating Parameter Uncertainty in Binding-Energy Models by the Frequency-Domain Bootstrap.
We propose using the frequency-domain bootstrap (FDB) to estimate errors of modeling parameters when the modeling error is itself a major source of uncertainty. Unlike the usual bootstrap or the simple χ^{2} analysis, the FDB can take into account correlations between errors. It is also very fast compared to the Gaussian process Bayesian estimate as often implemented for computer model calibration. The method is illustrated with a simple example, the liquid drop model of nuclear binding energies. We find that the FDB gives a more conservative estimate of the uncertainty in liquid drop parameters than the χ^{2} method, and is in fair accord with more empirical estimates. For the nuclear physics application, there are no apparent obstacles to apply the method to the more accurate and detailed models based on density-functional theory.


Pressures and rewards of working in community mental health teams.
Community mental health teams (CMHTs) are widely regarded as the mainstay of community services, bringing health and social services professionals together to target people with severe mental health problems. Heather Harper and Edana Minghella report the findings of a recent survey looking at the pressures and rewards of working in these community-based, multi-disciplinary teams.


Bilateral organization of physiological tremor in the upper limb.
The bilateral patterns of physiological tremor in the upper limb of adults were examined under conditions where eight combinations of the elbow, wrist and index-finger joints of the right arm were braced using individually molded splints. The hypotheses tested were that: (a) coordination of upper-limb tremor involves (compensatory) coupling of intra- but not inter-limb segments, (b) splinting the respective joints of the right arm changes the organization of this synergy in both limbs, and (c) reducing the involvement of joint-space degrees of freedom through restricting their motion (by splinting) results in increased tremor in the distal segments. Under no-splinting conditions, significant relationships were only observed between adjacent (intra-limb) effector units, with the strength of the correlation increasing from proximal to distal. Splinting the right limb resulted in an increase in the strength and number of significant intra-limb relationships in both limbs. No inter-limb tremor relationships were found between any segment during this task, irrespective of the splinting condition. The frequency profile for the tremor in each limb segment showed two prominent frequency peaks (at 2-4 Hz and 8-12 Hz). A third, higher frequency peak (18-22 Hz) was observed in the index fingers only. Splinting the right limb produced a general increase in the amplitude and variability of tremor in the fingertip of both arms. This effect was particularly strong under conditions where the more proximal joints were splinted. The lack of any between-limb relationships, coupled with the fact that splinting one limb influenced both limbs, suggests that some form of linkage does exist between the limbs. It is unlikely that mechanical linkages can explain fully these relationships. It is proposed that the tremor observed in either limb represents the output of a central oscillatory mechanism(s), but that this output is subsequently independently filtered in a parallel fashion on its way to each respective limb. A common bilateral (compensatory) strategy is employed to minimize the tremor in either limb during this multiple-degrees-of-freedom task.


Improving quality of care in osteoporosis: opportunities and challenges.
Osteoporosis is a chronic disease with a projected escalation in fracture prevalence and costs as the population ages. Osteoporosis care aims to prevent fractures and ultimately improve health-related quality of life. Despite significant evidence-based advances in testing and treatment, a large proportion of patients with fragility fracture or other osteoporosis risk factors are never evaluated with bone mineral density measurement testing and never receive therapy. This suboptimal quality of care can be attributed to barriers at the patient, provider, and health system levels. In addition, significant disparities in care exist across age, ethnicity, and gender. Recent studies have indicated that restructuring care at the system level is more likely to be successful, dependable, and durable than traditional quality improvement interventions focusing predominantly on physicians.


Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad.
A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality.


A dissolution rate apparatus for the prediction of initial drug absorption patterns in beagles: tolbutamide tablets.
An apparatus utilizing liquid turbulence to simulate hydrodynamic conditions generated by gastrointestinal peristalsis was designed to estimate drug release from solid oral dosage forms; This turbulence was achieved through special arrangements of a pipetting pump to a dissolution chamber. By adjusting the flow rate of the pump to deliver and withdraw a fixed volume of dissolution medium per minute, a correlation was developed between dissolution rates and absorption patterns in beagles of two commerical tolbutamide tablets, A and B, and a micronized tolbutamide suspensionmon the basis of this relationship, it was possible to predict the initial absorption patterns of two misformulated tablets, C and D.


Karyotype abnormalities and their clinical significance in a group of chronic myeloid leukemia patients treated with hematopoietic stem cell transplantation.
Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5%). Among these, 23 (82.3%) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.


[Infrared spectroscopy technology, one of the faster and more convenient methods to detect the stability of stored Niuxi].
To detect the change of Niuxi in reserve and establish one easier method of evaluating the quality change of Niuxi. Infrared spectroscopy and compare software were used to distinguish the different Niuxi, and simulation testing were used to observe calefactive stability. There were obvious difference between transmutative and normal Niuxi, and Niuxi had evident change when the temperature above 140 degrees C in the simulation testing. Infrared spectroscopy can be used to evaluae the quality stability of Niuxi. It is one tried method to provide the establishment of reserve and torrefaction conditions.


RCN call to 'value nurses' in Scotland.
Nurses and midwives in Scotland are pressing the Scottish Executive to fund in full return to practice courses. The calls have come in support of an RCN Scotland campaign 'Value Nurses'.


Influence of phenytoin on the disposition of irinotecan: a case report.
Irinotecan (CPT-11), a water-soluble topoisomerase I inhibitor, is metabolized by carboxylesterase enzymes to form an active metabolite, SN-38. Recent studies have shown that irinotecan also undergoes oxidative metabolism by the P450 isozyme CYP3A4, leading to the formation of a minor inactive metabolite, 7-ethyl-10-[4-N-[(5-aminopentanoic acid)-1-piperidino]-carbonyloxy-camptothecin (APC). The elucidation of this metabolic pathway suggests the potential for drug interactions when irinotecan is administered with other inducers or substrates of CYP3A4. In this report, the authors summarize the pharmacokinetic profile of irinotecan and its major metabolites with and without concomitant phenytoin administration in an individual patient. These studies revealed that concomitant phenytoin administration resulted in a marked decrease in the systemic exposure to irinotecan and SN-38 and an increase in the exposure to APC. The area under the curve of irinotecan and SN-38 decreased by 63% and 60%, respectively; the area under the curve of APC increased by approximately 16%. Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population.


A cone beam CT-guided online plan modification technique to correct interfractional anatomic changes for prostate cancer IMRT treatment.
The purpose of this work is to develop an online plan modification technique to compensate for the interfractional anatomic changes for prostate cancer intensity-modulated radiation therapy (IMRT) treatment based on daily cone beam CT (CBCT) images. In this proposed technique, pre-treatment CBCT images are acquired after the patient is set up on the treatment couch using an in-room laser with the guidance of the setup skin marks. Instead of moving the couch to rigidly align the target or re-planning using the CBCT images, we modify the original IMRT plan to account for the interfractional target motion and deformation based on the daily CBCT image feedback. The multileaf collimator (MLC) leaf positions for each subfield are automatically adjusted in the proposed algorithm based on the position and shape changes of target projection in the beam's eye view (BEV). Three typical prostate cases were adopted to evaluate the proposed technique, and the results were compared with those obtained with bony-structure-based rigid translation correction, prostate-based correction and CBCT-based re-planning strategies. The study revealed that the proposed modification technique is superior to the bony-structure-based and prostate-based correction techniques, especially when interfractional target deformation exists. Its dosimetric performance is closer to that of the re-planned strategy, but with much higher efficiency, indicating that the introduced online CBCT-guided plan modification technique may be an efficient and practical method to compensate for the interfractional target position and shape changes for prostate IMRT.


[Efficacy of naftopidil for nocturia and consequent sleep disturbance in patients with benign prostatic hyperplasia].
Nocturnal urinary frequency is a predominant complaint among males presenting with benign prostatic hyperplasia (BPH), which markedly impacts quality of life (QOL) and often causes sleep disturbance. We studied the efficacy of naftopidil an alpha 1-adrenoreceptor antagonist used for treatment of BPH for improvement of nocturia and consequent sleep disturbance. Twenty-five patients diagnosed with BPH were administered daily oral doses of naftopidil (50 or 75 mg/day) for eight weeks. The symptoms were assessed quantitatively using the following criteria : International Prostate Symptoms Score (I-PSS), QOL index, frequency volume chart, and Pittsburgh Sleep Quality Index (PSQI). After treatment, the mean+/-SD of total I-PSS and nocturia decreased from 16.9+/-5.2 to 10.3+/-4.9 (p<0.001) and 3.5+/-1.2 to 2.3+/-1.3 (p<0.001), respectively. In addition, all categories of storage symptoms in I-PSS were also significantly improved. PSQI results were obtained in 21 of the 25 patients, and decreased from 6.4+/-4.2 to 5.3+/-3.5 (p=0.026) (normal range: less than 5.5). This is the first report of a quantitative analysis of the effect of naftopidil on sleep quality in BPH patients. In conclusion, naftopidil appears to be an effective agent not only for nocturia and other urinary storage symptoms, but also for improving the quality of sleep.


Carrier ampholyte-free solution isoelectric focusing as a prefractionation method for the proteomic analysis of complex protein mixtures.
The field of proteomics requires methods that offer high sensitivity and wide dynamic range. One of the strategies used to improve the dynamic range is sample prefractionation, such as microsolution isoelectric focusing (IEF). We have modified a commercial solution IEF instrument, the Rotofor, to prefractionate protein mixtures by carrier ampholyte-free solution IEF. The focusing chamber of the Rotofor was divided into several compartments by polyacrylamide membranes with imbedded Immobiline mixtures of specific pH values. When an electric field is applied, each protein migrates to the compartment confined by membranes with pH values flanking its isoelectric point. The approach was demonstrated for the focusing of myoglobin into a predicted compartment, as well as the separation of a complex soluble yeast protein mixture into several distinct fractions. The proteins were dissolved in water or 30% isopropanol. The method is applicable to both gel-based and solution-phase protein identification methods, without the need for further sample preparation.


[Infection by human herpesvirus type 6 (HHV-6) and renal transplantation].
Human herpes virus type 6 (HHV-6) infection was serologically investigated in renal transplant recipients. Before transplantation, 75.5% of patients was seropositive for HHV-6 and no correlation with age, sex and time on dialysis was found. During the first month after transplantation 66% of patients showed a variation in serological status against HHV-6 (seroconversion or fourfold increase of antibody titer). All patients who seroconverted had received the kidney from a HHV-6 seropositive donor, furthermore, in 11/13 (84.6%) pairs of patients receiving the kidney form the same seropositive donor, both members or had HHV-6 active infection or had no infection. The frequency of HHV-6 active infection in seropositive patients is almost the same in case of seronegative or seropositive donor. Comparing HHV-6 and CMV infections, they resulted independent as CMV infection in these patients occurs in a following period (II-III month). Notwithstanding a higher frequency of kidney rejection in patients with active HHV-6 infection, no significative correlation was found.


Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo.
In mammals, Pax3, Six4, Six1 and Six5 genes are co-expressed with Eya1, Eya2 and Eya4 genes during mouse somitogenesis. To unravel the functions of Eya genes during muscle development, we analyzed myogenesis in Eya2-/- and in Eya1-/- embryos. A delay in limb myogenesis was observed between E10 and E13 in Eya1-/- embryos only, that is later compensated. Compound E18 Eya1-/-Eya2-/+ fetuses present a muscle phenotype comparable with that of Six1-/- fetuses; lacking a diaphragm and with a specific absence of limb muscles, suggesting either genetic epistasis between Six and Eya genes, or biochemical interactions between Six and Eya proteins. We tested these two non-exclusive possibilities. First, we show that Six proteins recruit Eya proteins to drive transcription during embryogenesis in the dermomyotomal epaxial and hypaxial lips of the somites by binding MEF3 DNA sites. Second, we show that Pax3 expression is lost in the ventrolateral (hypaxial) dermomyotomes of the somite in both Eya1-/-Eya2-/- embryos and in Six1-/-Six4-/- embryos, precluding hypaxial lip formation. This structure, from which myogenic cells delaminate to invade the limb does not form in these double mutant embryos, leading to limb buds without myogenic progenitor cells. Eya1 and Eya2, however, are still expressed in the somites of Six1Six4 double mutant and in splotch embryos, and Six1 is expressed in the somites of Eya1Eya2 double mutant embryos and in splotch embryos. Altogether these results show that Six and Eya genes lie genetically upstream of Pax3 gene in the formation of ventrolateral dermomyotome hypaxial lips. No genetic links have been characterized between Six and Eya genes, but corresponding proteins activate key muscle determination genes (Myod, Myogenin and Mrf4). These results establish a new hierarchy of genes controlling early steps of hypaxial myogenic commitment in the mouse embryo.


Differences in cocaine- and morphine-induced cognitive impairments and serum corticosterone between C57BL/6J and BALB/cJ mice.
Addictive drug exposure is associated with impairments in various cognitive domains. Murine models of drug-induced cognitive impairment have helped to inform research on interventions to attenuate such cognitive diminishment; however, while differences between the drug-induced cognitive impairments exhibited by C57BL/6J and BALB/cJ mice have been observed, they remain unclear. This study measured differences in cognitive behavior performance on the object recognition test (ORT) and social recognition test (SRT) and serum levels of corticosterone (CORT) between C57BL/6J and BALB/cJ mice after 14-day chronic exposure to either cocaine (5 mg/kg) or morphine (3 mg/kg) at a dosage of 10 ml/kg/day. The ORT revealed that cocaine and morphine exposure significantly reduced the discrimination ratio in both C57BL/6J and BALB/cJ mice, exploration time was only reduced in C57BL/6J mice: the exploration times of C57BL/6J mice from the control (p < 0.05), cocaine (p < 0.05), and morphine (p < 0.01) administration groups were significantly less than those of BALB/cJ mice. The SRT demonstrated that drug exposure significantly reduced exploration time (cocaine, p < 0.01; morphine, p < 0.01) and impaired social recognition in C57BL/6J mice. No significant effect in BALB/cJ mice was observed. Serum CORT levels were lower in control C57BL/6J mice than in control BALB/cJ mice (p < 0.05), but no difference was observed after drug administration. In conclusion, changes in object and social learning recognition indicate that C57BL/6J mice are more sensitive than BALB/cJ mice to chronic drug exposure, especially to cocaine; concomitant changes in serum CORT may mediate these effects.


Corrigendum
In a previous manuscript the staining pattern of a monoclonal antibody generated to the N-terminal sequence of the ORL-1 receptor was described in the rat CNS (Anton et al., 1996). Subsequently, this antibody was used in double-label confocal experiments to map mu opioid and ORL-1 receptors in areas of brain associated with pain processing (Monteillet-Agius et al., 1998). In order to stain sections in mice, the monoclonal antibody was biotinylated, and as one of the specificity controls, brain sections from mutant mice lacking the ORL-1 receptor were stained. Mice null for both exon 2 and 3 of the ORL-1 receptor (generated by Zhenping Chen in John Pintar's laboratory, UMDNJ-Robert Wood Johnson Medical School, unpublished) as well as exon 1 knockout mice, which eliminates the epitope to which the antibody was raised, (Nishi et al., 1997) were tested and the same results obtained. The biotinylated antibody showed a staining pattern in the ORL-1 knockout mice indistinguishable from wild-type mice and similar to the pattern found in rat brain. Although the CNS staining pattern in rat was consistent with the distribution of mRNA for the receptor, the retained staining pattern in ORL-1 null mice demonstrates that the monoclonal antibody is recognizing a protein distinct from the ORL-1 receptor.


Self-evaluation by community older adults on the applicability of the healthy beat acupunch exercise program.
Objectives To evaluate the applicability of the Healthy Beat Acupunch (HBA) exercise program for older adults at community care centers and to explore their perceived impacts and suggestions for program protocol after six months of HBA exercises. Design & setting This prospective and descriptive study recruited 113 older adults from four community care centers. Intervention The HBA exercises were conducted 3 times a week, 40 min per session, for six months. Main outcome measures The program evaluation focused on four criteria: simplicity, safety, suitability, and helpfulness of the three phases of the HBA program using a 10-point ladder scale. The semi-structured interviews were focused on the participants' exercise experiences, perceived impacts on their health, and suggestions for the HBA program protocol. Results The average scores of the four criteria in each phase of the program ranged between 9.59 and 9.98 points. Participants reported an increase in their limb flexibility (n = 31) and that they were more relaxed (n = 26) and more energetic (n = 26) after engaging in the HBA exercises. Most of the participants suggested that the HBA program should be offered three times a week, 40 min per session, with 30 people in a group, and led by instructors who were professional, hardworking, easygoing, and enthusiastic, regardless of gender and age. Conclusions The HBA program was rated at a high level of simplicity, safety, suitability, and helpfulness by community older adults, which indicated that the program was considered as appropriate and applicable for the older population.


Food-based oral rehydration salt solution for acute childhood diarrhoea.
The efficacy in acute childhood diarrhoea of oral rehydration therapy (ORT) based on staple foods (maize, millet, wheat, sorghum, rice, or potato) was compared with that of standard ORT based on glucose. 266 children aged 1-5 years, with a history of acute diarrhoea for 48 h or less, moderate to severe dehydration, and no complications, were assigned to treatment with one of the food-based oral rehydration salt solutions (ORS) or standard ORS. The mean stool output over the first 24 h of treatment in the group receiving standard ORS was significantly higher than that of any other treatment group, and the groups receiving food-based ORT showed substantial reductions in stool output compared with the standard ORT group. Abnormalities in electrolyte concentrations were corrected in all treatment groups with similar efficiency. The digestibility of the food-based ORS was assessed by the stool pH, glucose content before and after acid hydrolysis, and osmolality; there were no significant differences between the standard ORS and food-based ORS groups. Food-based ORT should be more acceptable to users in developing countries since the mixtures are similar to traditional weaning foods and since, unlike standard ORT, it reduces stool output substantially.


MPer1 and mper2 are essential for normal resetting of the circadian clock.
Mammalian Per1 and Per2 genes are involved in the mechanism of the circadian clock and are inducible by light. A light pulse can evoke a change in the onset of wheel-running activity in mice by shifting the onset of activity to earlier times (phase advance) or later times (phase delays) thereby advancing or delaying the clock (clock resetting). To assess the role of mouse Per (mPer) genes in circadian clock resetting, mice carrying mutant mPer1 or mPer2 genes were tested for responses to a light pulse at ZT 14 and ZT 22, respectively. The authors found that mPer1 mutants did not advance and mPer2 mutants did not delay the clock. They conclude that the mammalian Per genes are not only light-responsive components of the circadian oscillator but also are involved in resetting of the circadian clock.


Inhibition of biotransformation of xenobiotic p-nitroanisole after cryopreservation of isolated rat hepatocytes.
Cryopreservation of isolated rat hepatocytes with dimethyl sulfoxide (Me2SO) using a rapid two-step freezing protocol allows significant preservation of cell recovery and xenobiotic p-nitroanisole (p-NA) metabolism. A decrease in the rate of O-demethylation of p-NA after cryopreservation correlates with a change in cellular viability. A freeze-thaw procedure in the absence of a cryoprotectant results in a sharp inhibition and subsequent washing causes a complete loss of the ability of cells to metabolize the xenobiotic. In the presence of exogenous NADPH the rate of p-NA biotransformation is restored. The content of cytochrome P-450 does not change during a hepatocyte freeze-thaw procedure in the presence or absence of Me2SO. Separation of cells after cryopreservation using a Percoll solution permits the isolation of a suspension, the viability of which does not differ from that of the freshly isolated control, but which metabolizes p-NA at a slower rate. During incubation, viability of cryopreserved cells was reduced. The data indicate that inhibition of monooxygenative activity after hepatocyte cryopreservation results from the loss of endogenous reduced pyridine nucleotides. The loss of pyridine nucleotides results from damage of plasma membrane during both cryopreservation and subsequent incubation in the presence of xenobiotic.


Hard and soft tissue changes of osteomyelitis of the jaws on CT images.
This study aimed to assess the hard and soft tissue changes in osteomyelitis (OM) of the jaws using CT images. The CT images of 153 patients (59 males and 94 females) with OM of the jaws were retrospectively reviewed. The relationships between each space involvement, between space and muscle involvements, between cortical bone defect and space involvement, and between cortical bone defect and muscle involvement were evaluated. The cortical bone defect was more common on the buccal side in the maxilla and on the lingual side in the mandible. The most commonly involved muscle was the buccinator muscle in the maxilla and the masseter muscle in the mandible and the most frequently involved space was the buccal space followed by the masticator space. CT is a useful tool in evaluating both hard and soft tissue changes of OM of the jaws.


Externality and burnout among dentists.
This study investigates the relationship between burnout as measured by the Maslach Burnout Inventory and locus of control as measured by the Adult Nowicki-Strickland Internal-External Locus of Control (ANS-IE) for 82 dentists. Significant Pearson correlations between two Maslach subscales and locus of control show Personal Accomplishment to be negatively associated -.31 and Emotional Exhaustion to be positively correlated .21 to externality.


Adenosine Deaminases That Act on RNA (ADARs).
Inosine is one of the most common modifications found in human RNAs and the Adenosine Deaminases that act on RNA (ADARs) are the main enzymes responsible for its production. ADARs were first discovered in the 1980s and since then our understanding of ADARs has advanced tremendously. For instance, it is now known that defective ADAR function can cause human diseases. Furthermore, recently solved crystal structures of the human ADAR2 deaminase bound to RNA have provided insights regarding the catalytic and substrate recognition mechanisms. In this chapter, we describe the occurrence of inosine in human RNAs and the newest perspective on the ADAR family of enzymes, including their substrate recognition, catalytic mechanism, regulation as well as the consequences of A-to-I editing, and their relation to human diseases.


Interstitial deletion of 1q42.13-q43 with Duane retraction syndrome.
Duane retraction syndrome is a congenital eye movement disorder characterized by failure of the sixth cranial nerve or nucleus to develop properly, resulting in restriction of abduction, narrowing of the palpebral fissure, and retraction of the globe on attempted adduction and/or restricted adduction. The gene loci of Duane syndrome have been mapped on 8q and 2q, indicating a heterogeneity. We report here a patient with interstitial deletion of 1q with Duane syndrome. The karyotype of our patient suggests another possible locus of the Duane syndrome, and the mapped genes around the deleted region, 1q42.13-43, contain possible candidate genes such as a homeobox gene. However, further clinical descriptions of patients with Duane syndrome and genetic investigations of the deleted regions are needed for a more accurate delineation.


Feasibility of macrophage mediated on-demand drug release from surface eroding poly(ethylene carbonate).
Macrophage induced surface degradation of poly(ethylene carbonate) (PEC) was investigated under in vitro conditions. Degradation of PEC with the MW of 41 kDa (PEC41) was slower than that of PEC with the MW of 200 kDa (PEC200). In terms of macrophage mediated drug release from PEC matrix, in cell-free medium, less than 1% of levofloxacin was released from both PEC samples in 10 days, while more than 60 and 20% of the drug, levofloxacin, can be detected in medium with macrophages from PEC200 and PEC41 films, respectively. This work indicated that on-demand drug delivery induced by macrophages can be achieved with PEC polymer.


A study of the detection of sperm antibody in cervical mucus with a modified immunobead method.
To develop a new immunobead binding test (IBT) procedure that will detect sperm antibody in cervical mucus (CM), especially in very small samples of mucus. After the interaction of donor sperm with bromelin-dissolved CM, the motile sperm cells were separated from other cells and debris and then tested with a standard immunobead method. The CM and serum samples were obtained from a sequence of referred patients who were sent to this testing laboratory. There were 60 women who provided 64 samples of CM and 41 samples of blood serum. They were partners in infertile couples. None. A useful distinction was made between positive and negative results for the mucus samples by this CM-IBT procedure. The usable samples of mucus could be as little as 0.05 g (wet weight). From the 60 women, seven mucus samples were positive; in the repeated testing, the same results were obtained with five of the six positive samples and seven of seven negative samples. This method (CM-IBT) can be clinically useful for detecting sperm antibody in CM, especially because it is effective for tiny samples. In this method, the motile sperm cells are better separated from the debris after the incubation step. When the IBT was applied to the serum samples from the same women, there was no correlation between serum-IBT and CM-IBT, showing that both materials must be tested.


Cancer-Associated Fibroblasts Accelerate Malignant Progression of Non-Small Cell Lung Cancer via Connexin 43-Formed Unidirectional Gap Junctional Intercellular Communication.
Gap junctions, which are assembled by connexins, can directly connect the cytoplasm of adjacent cells and enable gap junctional intercellular communication (GJIC) as well as metabolic coupling between neighboring cells. Here, we investigated the role of connexin 43 (Cx43) and its derived GJIC in the interplay between non-small cell lung cancer (NSCLC) cells and cancer-associated fibroblasts (CAFs). CAFs and NSCLC cells were co-cultured with direct contact and separated using flow cytometry. Glucose uptake, lactate production, and the expression and activity of PKM-2 and LDH-A in sorted CAFs were measured by a colorimetric assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Meanwhile, E-cadherin and N-cadherin expression and the migration and invasion of sorted NSCLC cells were detected by western blotting, wound width, and Transwell assays. Pyruvate, acetyl-CoA, and citric acid levels, ATP levels, and LDH-B and α-KG activity in sorted NSCLC cells were determined by a colorimetric or fluorometric assay and ELISA, respectively. Functional GJIC between cells and the subcellular location of connexins were detected by a "Parachute" assay and immunofluorescence. Levels of α-SMA, Cx43, and LDH-B in tissue from patients with NSCLC were determined by immunohistochemistry. Cx43 accumulated in the plasma membrane, which favored the assembly of asymmetric unidirectional GJIC from CAFs to NSCLC cells. CAFs underwent increased aerobic glycolysis and promoted the epithelial-mesenchymal transition, migration, and invasion of NSCLC cells. In contrast, NSCLC cells experienced enhanced oxidative phosphorylation upon CAF stimulation, with an increase in ATP generation and thereby activation of the PI3K/Akt and MAPK/ERK pathways. Metabolic coupling between CAFs and NSCLC cells was under the strict control of Cx43-formed unidirectional GJIC. Patients with high tri-expression of α-SMA, Cx43, and LDH-B had the shortest overall survival and relapse-free survival compared with those with individual overexpression or high bi-expression. Cx43-formed unidirectional GJIC plays a critical role in mediating close metabolic cooperation between CAFs and NSCLC cells to support the malignant progression of NSCLC.


At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction.
Starting from the well-documented effects of marijuana smoking on heart rate and blood pressure, the cardiovascular effects of Δ⁹-tetrahydrocannabinol (THC, the main psychotropic ingredient of Cannabis) and endocannabinoids [THC endogenous counterparts that activate cannabinoid receptor type 1 (CB₁) and 2 (CB₂)] have been thoroughly investigated. These studies were mostly aimed at establishing the molecular bases of the hypotensive actions of THC, endocannabinoids and related molecules, but also evaluated their therapeutic potential in cardiac injury protection, metabolic cardiovascular risk factors and atherosclerotic plaque vulnerability. The results of these investigations, reviewed here, also served to highlight some of the most peculiar aspects of endocannabinoid signaling, such as redundancy in endocannabinoid targets and the often dualistic role of CB₁ and CB₂ receptors during pathological conditions.


Physical modalities for complex regional pain syndrome.
Hand therapy is the backbone of a treatment program for complex regional pain syndrome. Various treatment techniques and physical modalities are described in the framework of a clear set of treatment goals. Hand therapy is often the only treatment necessary for simple cases. Adjunct treatments, such as injections or other pharmacologic agents, may be needed when pain control is problematic.


The Disgust Propensity and Sensitivity Scale-Revised: an examination of a reduced-item version.
The Disgust Propensity and Sensitivity Scale-Revised (DPSS-R [Pers. Indiv. Differ. 41 (2006) 1241-1252]) is a new assessment tool thought to assess two distinguishable factors contributing to disgust reactions, Disgust Propensity and Disgust Sensitivity. Extant data though indicate the presence of four unreliable DPSS-R items. The present study examined the psychometric properties of a reduced-item version of the DPSS-R, in which these four problematic items were removed, using data from two large independent samples of nonclinical college students. Results from Study 1 revealed that the reduced-item DPSS-R factor structure provided more favorable goodness-of-fit indices than the two previous full-length DPSS-R factor structures. In Study 2, the reduced-item DPSS-R scales showed good reliability, stronger relationships with symptoms of disgust-relevant than fear-relevant phobias, and adequate incremental concurrent validity in predicting symptoms of disgust-relevant phobias. The present study suggests that the reduced-item DPSS-R is both reliable and valid, and likely addresses the limitations of the full-length version.


Functional absence of extraocular photoreception in hamster circadian rhythm entrainment.
The mammalian circadian pacemaker is entrainable by light via the retina. The putative role of extraocular light perception was investigated in blinded hamsters. These animals were shaved and exposed to a light-emitting pad for either 30 min or 3 h. The absence of any phase-shifting effects on wheel running activity rhythms indicates that extraocular light perception plays no functional role in photic entrainment of the circadian pacemaker in the hamster.


[Treatment of hepatitis C - an imminent revolution].
Treatment of hepatitis C is approaching a revolution. During the last years, many agents have been developed that directly interfere with the viral replication cycle. Therapy of hepatitis C will no longer need Interferon in the future. The new therapies will be shorter, more efficient and with fewer side effects. For patients, the burden of treatment will drop substantially. Even patients are traditionally classified who as "difficult to treat", such as cirrhotic patients, HIV/hepatitis C coinfected patients and patients after liver transplantation will have better chances of cure. For more patients to benefit from the new therapies, identification of infected individuals and diagnostic investigations have to be improved.


Double-Shelled TiO2 Hollow Spheres Assembled with TiO2 Nanosheets.
High-quality double-shelled TiO2 hollow spheres (DHS-Ti) assembled with TiO2 nanosheets have been synthesized for the first time through a simple hydrothermal treatment of sSiO2 @TiO2 (TiO2 -coated solid SiO2 spheres). The double-shelled structure shows a high BET surface area up to 417.6 m2 g-1 . Anatase DHS-Ti of high crystallinity can be obtained without structural collapse by calcination treatment. The effects of cetyl trimethylammonium bromide (CTAB) concentration, pH, and hydrothermal reaction temperature have also been investigated with a series of contrast experiments. A formation mechanism involving the in situ growth of amorphous TiO2 nanosheets followed by the redeposition of dissolved silica species is proposed. Lastly, the DHS-Ti forming strategy can be extended as a general strategy to fabricate various morphological hollow nanostructures and double-shelled Pt nanocatalysts by rationally selecting functional sSiO2 nanoparticles as core materials. This work could open up a new strategy for controllable synthesis of complex hollow structures and other functional materials.


Early life sensory ability-ventilatory responses of thornback ray embryos (Raja clavata) to predator-type electric fields.
Predator avoidance is fundamental for survival and it can be particularly challenging for prey animals if physical movement away from a predatory threat is restricted. Many sharks and rays begin life within an egg capsule that is attached to the sea bed. The vulnerability of this sedentary life stage is exacerbated in skates (Rajidae) as the compulsory ventilatory activity of embryos makes them conspicuous to potential predators. Embryos can reduce this risk by mediating ventilatory activity if they detect the presence of a predator using an acute electrosense. To determine how early in embryonic life predator elicited behavioral responses can occur, the reactions of three different age groups (1/3 developed, 2/3 developed, and near hatching) of embryonic thornback rays Raja clavata were tested using predator-type electric field stimuli. Egg capsules were exposed to continuous or intermittent stimuli in order to assess varying predator-type encounter scenarios on the ventilatory behavior of different developmental stages. All embryos reacted with a "freeze response" following initial electric field (E-field) exposure, ceasing ventilatory behavior in response to predator presence, demonstrating electroreceptive functionality for the first time at the earliest possible stage in ontogeny. This ability coincided with the onset of egg ventilatory behavior and may represent an effective means to enhance survival. A continuous application of stimuli over time revealed that embryos can adapt their behavior and resume normal activity, whereas when presented intermittently, the E-field resulted in a significant reduction in overall ventilatory activity across all ages. Recovery from stimuli was significantly quicker in older embryos, potentially indicative of the trade-off between avoiding predation and adequate respiration. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 721-729, 2016.


The differing prognostic utility of exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction.
Previous studies have documented the prognostic utility of left ventricular ejection fraction response to exercise primarily in populations without prior myocardial infarction. We undertook a study to assess the prognostic utility of exercise left ventricular ejection fraction and segmental wall motion response during exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction. We examined the comparative prognostic utility of left ventricular ejection fraction and segmental wall motion response during upright bicycle exercise radionuclide ventriculography in 419 coronary artery disease patients with (n = 217) and without (n = 202) prior myocardial infarction using univariate and multivariate hierarchical regression analyses. During an average followup period of 61 months, 96 patients (23%) suffered cardiac events, including 55/217 (25%) of the patients with prior myocardial infarction and 41/200 (21%) of the patients without prior myocardial infarction (p = ns). Both cumulative Kaplan-Meier survival analyses and stepwise hierarchical Cox survival analyses demonstrated that peak left ventricular ejection fraction < 55% was a significant predictor of cardiac events in patients without prior myocardial infarction (p = 0.04), whereas an exercise wall motion worsening score > or = 2 was a significant predictor in patients with a prior myocardial infarction (p = 0.0001). The prognostic utility of exercise radionuclide ventriculography variables differ according to the presence or absence of prior myocardial infarction. Global function, assessed by peak left ventricular ejection fraction, adds the greatest prognostic information in patients without prior myocardial infarction, whereas regional function, assessed by exercise wall motion worsening, is the best predictor among patients with prior myocardial infarction.


The dependence on the distance of shortening of the energy output from frog skeletal muscle shortening at velocities of Vmax, 1/2Vmax and 1/4Vmax.
Shortening heat and work were measured, during and after the shortening, in contractions in which muscles shortened various distances (all ending at 2.05 micron of sarcomere length) at various velocities. Shortening heat and work were produced as a non-linear function of the distance shortened at velocities greater than 1/ 2Vmax , which was probably caused by a redistribution of the crossbridge population to different state(s) during the approach to the steady state.


Probing Structural Changes during Self-assembly of Surface-Active Hydrophobin Proteins that Form Functional Amyloids in Fungi.
Hydrophobins are amphiphilic proteins secreted by filamentous fungi in a soluble form, which can self-assemble at hydrophilic/hydrophobic or water/air interfaces to form amphiphilic layers that have multiple biological roles. We have investigated the conformational changes that occur upon self-assembly of six hydrophobins that form functional amyloid fibrils with a rodlet morphology. These hydrophobins are present in the cell wall of spores from different fungal species. From available structures and NMR chemical shifts, we established the secondary structures of the monomeric forms of these proteins and monitored their conformational changes upon amyloid rodlet formation or thermal transitions using synchrotron radiation circular dichroism and Fourier-transform infrared spectroscopy (FT-IR). Thermal transitions were followed by synchrotron radiation circular dichroism in quartz cells that allowed for microbubbles and hence water/air interfaces to form and showed irreversible conformations that differed from the rodlet state for most of the proteins. In contrast, thermal transitions on hermetic calcium fluoride cells showed reversible conformational changes. Heating hydrophobin solutions with a water/air interface on a silicon crystal surface in FT-IR experiments resulted in a gain in β-sheet content typical of amyloid fibrils for all except one protein. Rodlet formation was further confirmed by electron microscopy. FT-IR spectra of pre-formed hydrophobin rodlet preparations also showed a gain in β-sheet characteristic of the amyloid cross-β structure. Our results indicate that hydrophobins are capable of significant conformational plasticity and the nature of the assemblies formed by these surface-active proteins is highly dependent on the interface at which self-assembly takes place.


Syphilitic gummatous iridocyclitis.
We present a rare case of gummatous syphilitic iridocyclitis. The differential diagnosis, clinical characteristics, and treatment of this ocular disease are discussed.


Gradient-excitation encoding combined with frequency and phase encodings for three-dimensional ultra-low-field MRI.
Ultra-low-field magnetic resonance imaging (ULF MRI) in microtesla fields is a new technology with features unseen in tesla-range MRI. Instead of induction coils as sensors, superconducting quantum interference device (SQUID) sensors are used, providing a frequency-independent signal-to-noise ratio (SNR). Owing to its tolerance for large relative imaging-field inhomogeneities, electromagnet shimming is not necessary. ULF MRI can also be combined with magnetoencephalography (MEG) to image the brain with close to millimetre-millisecond resolution. In this paper, the hybrid MEG-MRI device developed at Aalto University will be presented, as well as a 3D imaging scheme combining gradient-excitation encoding with frequency and phase and encodings. It is noteworthy that, regarding the presented gradient-excitation encoding in ULF MRI, the kilohertz-range Larmor frequencies allow MR signals to propagate unattenuated through tissue, which is not the case in tesla-range MRI with Larmor frequencies even above 100 MHz. Thus, the presented encoding method is especially compatible with ULF MRI, where the use of three different encoding mechanisms for three-dimensional imaging is possible. The feasibility of image reconstruction with the gradient-excitation-encoding method is demonstrated by simulations.


Autocorrelation techniques in fetal monitoring.
Fetal monitors that feature autocorrelation have recently been introduced. This paper discusses autocorrelation and describes how it extracts periodic signals from a noisy background. An example of its performance under clinical conditions demonstrating advantages and limitations is discussed.


[The nature of evoked potentials, recorded at neocortical transplants].
Evoked potentials (EP) recorded from a barrelfield of adult rats were compared with those recorded from neocortical embryonal grafts 4-6 month after their transplantation into the barrelfield of adult rats. EPs at the surface of the intact barrelfield started with a positive component followed by a negative wave. EPs reversed their polarity at a depth of 0.4-1.0 mm from the cortical surface. EPs registered from the surface of grafts has the same latency as those in the intact barrelfield, but consisted exclusively of a negative component. It is concluded that though the simultaneously activated grafted neurons can generate local field potentials, their detection during EP recording is prevented as a result of diffuse neuronal organization of the grafts and they can be masked by passive current spreading from the adjacent intact areas of the host brain.


Laparoscopic temporary clipping of uterine and ovarian arteries for the treatment of interstitial ectopic pregnancy.
To assess the effect of laparoscopic temporary clipping of uterine and ovarian arteries for the treatment of interstitial ectopic pregnancy. A 29-year-old woman with vaginal bleeding and pelvic pain was admitted to the current clinic. She had secondary amenorrhea for nine weeks. Transvaginal ultrasonography revealed normal empty uterus and right interstitial ectopic pregnancy with viable embryo. Laparoscopic temporary clipping of uterine and ovarian arteries, interstitial pregnancy resection, and primary myometrial suturing was performed. Following dissection Latzko pararectal space for the visualization of both uterine arteries, four vascular clips were placed (two to uterine arteries, two to infundibulopelvic ligaments). Excision of interstitial pregnancy and primary myometrial suturing was performed with minimal blood loss. The patient was discharged from the hospital after one day without any remarkable complications. To the best of the authors' knowledge, this is the first case of interstitial pregnancy that was successfully treated by temporary laparoscopic clipping of uterine and ovarian vessels prior to interstitial ectopic pregnancy resection.


Economic burden and absenteeism from influenza-like illness in healthy households with children (5-17 years) in the US.
School children (5-17 years) function as vectors in influenza epidemics. The objective of this study was to quantify the burden of influenza-like illness (ILI) on US healthy households with school-aged children. The Medical Expenditure Panel Survey database of 1996-2002 was queried to compare annual total medical expenses and absenteeism incurred by otherwise healthy households with school-aged children that reported experiencing ILI to similar households that did not experience ILI. We identified 12,850 healthy households with at least one school-aged child. Households reporting one or more ILI episodes incurred $281.47 higher total annual medical expenses than those without an ILI. Employed members in households with ILI lost an average of 1.12 more workdays from their illness compared to those in the households without ILI. Furthermore, households with ILI in which all members were employed and medically insured lost an additional 0.89 workdays due to caring for other ill household members. School children in households with ILI missed 1.91 more school days annually and 4.87 more school days if the household had three or more students. The total annual additional cost to a household experiencing ILI, including medical expenses and productivity losses was $538.75 for fully employed and insured households and $424.83 if one or more members were unemployed or uninsured. ILI increase economic burden among households with school-aged children and lead to more school and workdays lost. Initiatives to vaccinate school-aged children should be explored.


Role of thyroid hormones in the effects of selenium on mood, behavior, and cognitive function.
Changes in thyroid function may affect mood, behavior, and cognitive function. Selenium is required for appropriate thyroid hormone synthesis, activation, and metabolism. Selenium status influences thyroid function. Selenium status also affects psychological condition and cognitive function. The author suggests that the effects of selenium status on mood, behavior, and cognition may be partly mediated by changes induced by selenium deficiency or selenium supplementation in thyroid function. Selenium deficiency decreases immunocompetence and promotes viral infections. The author proposes that patients who have a combination of depression, hypothyroidism, and increased susceptibility to viral infections, could reasonably be assessed for selenium deficiency, especially if they live in an area where the soil is low in selenium.


Sequencing the 500-kb GC-rich symbiotic replicon of Rhizobium sp. NGR234 using dye terminators and a thermostable "sequenase": a beginning.
Genomes of the soil-borne nitrogen-fixing symbionts of legumes [Azo(Brady)Rhizobium species] typically have GC contents of 59-65 mol%. As a consequence, compressions (up to 400 per cosmid) are common using automated dye primer shotgun sequencing methods. To overcome this difficulty, we have exclusively applied dye terminators in combination with a thermostable "sequenase" for shotgun sequencing GC-rich cosmids from pNGR234a, the 500-kbp symbiotic replicon of Rhizobium sp. NGR234. A thermostable sequenase incorporates dye terminators into DNA more efficiently than Taq DNA polymerase, thus reducing the concentrations needed (20- to 250-fold). Unincorporated dye terminators can simply be removed by ethanol precipitation. Here, we present data of pXB296, one of 23 overlapping cosmids representing pNGR234a. We demonstrate that the greatly reduced number of compressions results in a much faster assembly of cosmid sequence data by comparing assembly of the shotgun data from pXB296 and the data from another pNGR234a cosmid (pXB110) sequenced using dye primer methods. Within the 34,010-bp sequence from pXB296, 28 coding regions were predicted. All of them showed significant homologies to known proteins, including oligopeptide permeases, an essential cluster for nitrogen fixation, and the C4-dicarboxylate transporter DctA.


Enhanced depth imaging optical coherence tomography of intraocular tumors: from placid to seasick to rock and rolling topography--the 2013 Francesco Orzalesi Lecture.
To review enhanced depth imaging optical coherence tomography of intraocular tumors. Review of tumor surface topography and internal characteristics based on published reports and personal experience. Using enhanced depth imaging optical coherence tomography, choroidal nevus showed smooth moderate dome-shape and with overlying retinal pigment epithelial alterations, subretinal cleft, and photoreceptor loss. Choroidal melanoma was smooth, moderately dome-shaped, and with overlying "shaggy" photoreceptors. Choroidal metastasis showed "lumpy, bumpy" irregular surface topography, subretinal fluid, and shaggy photoreceptors. Choroidal hemangioma was smooth, acutely dome-shaped and with subretinal fluid and/or cystoid retinal edema. Choroidal lymphoma showed "placid, rippled, or seasick" surface, correlating with increasing tumor thickness. Choroidal osteoma displayed smooth undulating surface with intralesional lamellar lines and tubules, representing bone lamellae or vessels. Choroidal melanocytosis produced flat but uniformly thickened choroid with increased stromal density. Choroidal hemorrhage displayed slightly "scalloped" surface in the outer choroid. All choroidal tumors showed inward compression of the choroidal vasculature, except for hemangioma in which the vessels were expanded. Sclerochoroidal calcification arose within the sclera as a "rocky" or "rolling" topography and solitary idiopathic choroiditis appeared as a domed or "volcanic" focal scleral thickening, each causing intense choroidal compression. Retinal tumors such as small retinoblastoma, astrocytic hamartoma, and hemangioblastoma arose abruptly adjacent to normal retina. Exophytic retinoblastoma and retinal hemangioblastoma depicted a full-thickness disorganized retinal mass with normal retina draped over the margins. Flat astrocytic hamartoma arose within the nerve fiber layer, and thicker tumors involved full-thickness retina with "moth-eaten" or cavitary appearance. Retinal pigment epithelial lesions such as congenital hypertrophy of retinal pigment epithelial showed flat topography with transmission of light through lacunae, occasional subretinal cleft and uniform photoreceptor loss, whereas combined hamartoma of retina/retinal pigment epithelial showed "sawtooth" pattern of vitreoretinal traction leading to mini-peak or maxi-peak retinal folds. Enhanced depth imaging optical coherence tomography shows characteristic topographical and intralesional patterns that appear to be suggestive for selected intraocular tumors.


Red cell fragmentation syndrome with the use of subclavian hemodialysis catheters.
The red cell fragmentation syndrome can occur due to abnormalities of the heart or the blood vessels or vascular malformations. We describe three patients who developed symptomatic hemolytic anemia due to red cell fragmentation with the use of single-lumen subclavian hemodialysis catheters. Retrospective analysis of 75 other patients who had undergone dialysis through this catheter disclosed five additional cases. Red cell fragmentation appears to be associated with partial catheter occlusion by thrombus or development of a clot at the catheter tip or both. The fragmentation resolved in all cases on withdrawal of the catheter. All patients with this catheter should be closely monitored for the red cell fragmentation syndrome, and the catheter should be withdrawn if it develops. White cell fragmentation was also seen in one patient.


Pelvic reconstruction after abdominoperineal resection: a pilot study using an absorbable synthetic prosthesis.
Abdominoperineal resection (APR) is not free of complications, in particular complications due to the occupation of the pelvis by the small bowel after surgery. A number of surgical techniques have been described to prevent the small bowel from entering and adhering to the pelvis (pelvic partition), but there is no agreement concerning their use. The aim of this study was to evaluate the feasibility, effectiveness and safety of using an absorbable synthetic prosthetic material for pelvic partitioning after APR. A prospective non-randomised longitudinal pilot study was carried out on a series of 10 patients who underwent APR due to lower-third rectal cancer, in order to evaluate the feasibility, safety and efficacy of pelvic partitioning with an absorbable synthetic prosthetic material. In all the patients, it was possible to perform a radical resection and to install the prosthesis. After a mean follow-up of 9 months (range: 4-18 months), no abdominal or perineal complications were detected. One patient (10%) suffered chronic pelvic pain. Pelvic partition after APR of the rectum with an absorbable synthetic prosthesis is feasible, effective and safe.


Non-islet cell hypoglycemia.
NICTH is a fairly uncommon disorder but has been well characterized and the molecular mechanisms involved have given insights into the IGF system, both normal and abnormal. NICTH has brought together the molecular biologists and endocrinologists in a classic cross cultural coordination to study the disorder from all angles and to further understand the disorder.


A novel therapy for the treatment of pyoderma gangrenosum.
Pyoderma gangrenosum (PG) is an uncommon, chronic, painful, ulcerative skin disease of unknown origin, often associated with systemic diseases including inflammatory bowel disease, rheumatoid arthritis; monoclonal gammopathy, hepatitis and myeloproliferative disorders. The mainstay of therapy for PG has been high-dose corticosteroids but not all patients have a favourable outcome. Other systemic agents have also been used such as cyclosporine, azathioprine, cyclophosphamide and tacrolimus. However, all these systemic therapies can be complicated by serious side effects. In this paper, we report a series of four patients with pyoderma gangrenosum treated successfully with topical cyclosporine. No side-effects were observed in any of the patients and there was minimal systemic absorption of the topical cyclosporine.


Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune.
Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was verified to involve in chemotherapy resistance in non-small cell lung cancer (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is recognized to boost immune and has anti-cancer activity against a majority of carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could attenuate the PD-L1 expression induced by resistance to cisplatin and draw out the underlying mechanisms of PD-L1 in this process. Human lung cancer cell lines A549 and A549/DDP (cisplatin-resistance) were used. Cell viability was detected by MTT assay, the PD-L1, Akt and NF-κB p65 protein expression were detected using Western blot analysis, the T cells cytotoxity to tumor cells was detected by crystal violet staining living residual tumor cells after coculture of tumor cells and T cells. The results showed that Rg3 could inhibit the growth and alleviate the resistant to cisplatin of A549/DDP cells. PD-L1 was overexpression in A549/DDP cells than A549 cells. Rg3 could decrease the PD-L1 expression induced by chemoresistance and resume the T cells cytotoxity to cancer cells. NF-κB p65 and Akt were involved in the PD-L1 overexpression and restrained by Rg3. Therefore, Rg3 could be regarded as a new agent targeting PD-L1 in chemotherapy refractory NSCLC.