TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity.
The aggregation of α-synuclein plays a major role in Parkinson disease (PD) pathogenesis. Recent evidence suggests that defects in the autophagy-mediated clearance of α-synuclein contribute to the progressive loss of nigral dopamine neurons. Using an in vivo model of α-synuclein toxicity, we show that the PD-like neurodegenerative changes induced by excess cellular levels of α-synuclein in nigral dopamine neurons are closely linked to a progressive decline in markers of lysosome function, accompanied by cytoplasmic retention of transcription factor EB (TFEB), a major transcriptional regulator of the autophagy-lysosome pathway. The changes in lysosomal function, observed in the rat model as well as in human PD midbrain, were reversed by overexpression of TFEB, which afforded robust neuroprotection via the clearance of α-synuclein oligomers, and were aggravated by microRNA-128-mediated repression of TFEB in both A9 and A10 dopamine neurons. Delayed activation of TFEB function through inhibition of mammalian target of rapamycin blocked α-synuclein induced neurodegeneration and further disease progression. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function, and highlight TFEB as a key player in the induction of α-synuclein-induced toxicity and PD pathogenesis, thus identifying TFEB as a promising target for therapies aimed at neuroprotection and disease modification in PD.


Quantitation of the volume of liquid injected into cells by means of pressure.
The amount of TRITC-labeled bovine serum albumin (TRITC-BSA) released from the tip of standardized microcapillaries at different injection pressures and times was investigated. Three test systems were used: (a) formation of droplets of the test solution (TRITC-BSA) in paraffin oil, (b) injection of the test solution into buffer droplets suspended in paraffin oil, and (c) injection into living 3T3 cells. The amount of test substance released was determined by scanning fluorometry. The first procedure (a) allows the fluorometrically determined amount of TRITC-BSA to be related to the volume of released test solution. For this rather large pressures (about 700 hPa) are required to overcome the surface forces counteracting droplet formation. The volume of the spheres was evaluated from photomicrographs of the droplets. The values obtained correlate very well with those determined by measuring the fluorescence emitted by the droplets. Injection into preformed droplets of buffer (b) can be performed with pressures in the range used for injecting cells (50-400 hPa). High reproducibility in the volume released is obtained with a single microcapillary; however, large variations exist between different capillaries, although these should theoretically be of equal diameter. The volume injected into living cells (c) under a given condition may vary by a factor of 5 or more. This variation may be due to viscosity differences of cytoplasm. We recommend, therefore, injection of fluorescent marker substances together with the test substance, enabling the injected volume to be determined by scanning fluorometry or by image analysis.


Electrocatalytic CO2 Reduction with a Binuclear Bis-Terpyridine Pyrazole-Bridged Cobalt Complex.
A pyrazole-based ligand substituted with terpyridine groups at the 3 and 5 positions has been synthesized to form the dinuclear cobalt complex 1, that electrocatalytically reduces carbon dioxide (CO2 ) to carbon monoxide (CO) in the presence of Brønsted acids in DMF. Chemical, electrochemical and UV-vis spectro-electrochemical studies under inert atmosphere indicate pairwise reduction processes of complex 1. Infrared spectro-electrochemical studies under CO2 and CO atmosphere are consistent with a reduced CO-containing dicobalt complex which results from the electroreduction of CO2 . In the presence of trifluoroethanol (TFE), electrocatalytic studies revealed single-site mechanism with up to 94 % selectivity towards CO formation when 1.47 M TFE were present, at -1.35 V vs. Saturated Calomel Electrode in DMF (0.39 V overpotential). The low faradaic efficiencies obtained (<50 %) are attributed to the generation of CO-containing species formed during the electrocatalytic process, which inhibit the reduction of CO2 .


The degradation and clearance of Poly(N-hydroxypropyl-L-glutamine)-DTPA-Gd as a blood pool MRI contrast agent.
Although polymeric magnetic resonance imaging (MRI) agents have significantly improved relaxivity and prolonged circulation time in vivo compared with current imaging agents, the potential for long-term toxicity prevents their translation into the clinic. The aim of this study was to develop a new biodegradable, nonionic polymeric blood pool MRI contrast agent with efficient clearance from the body. We synthesized PHPG-DTPA, which possesses two potentially degradable sites in vivo: protein amide bonds of the polymer backbone susceptible to enzymatic degradation and hydrolytically labile ester bonds in the side chains. After chelation with Gd(3+), PHPG-DTPA-Gd displayed an R(1) relaxivity of 15.72 mm(-1)⋅sec(-1) (3.7 times higher than that of Magnevist(T)). In vitro, DTPA was completely released from PHPG polymer within 48 h when incubated in mouse plasma. In vivo, PHPG-DTPA-Gd was cleared via renal route as shown by micro-single photon emission computed tomography of mice after intravenous injection of (111)In-labeled PHPG-DTPA-Gd. MRI of nude rats bearing C6 glioblastoma showed significant enhancement of the tumor periphery after intravenous injection of PHPG-DTPA-Gd. Furthermore, mouse brain angiography was clearly delineated up to 2 h after injection of PHPG-DTPA-Gd. PHPG-DTPA-Gd's biodegradability, efficient clearance, and significantly increased relaxivity make it a promising polymeric blood pool MRI contrast agent.


Are calcium-channel blockers effective in the treatment of tardive dyskinesia?
To review the data describing the use of calcium-channel blockers in the treatment of tardive dyskinesia (TD). A MEDLINE search of the English-language literature and a bibliographic review of pertinent articles examining the use of calcium-channel blockers in the treatment of TD were performed. Medical Subject Headings (MESH) terms used were calcium-channel blockers, tardive dyskinesia, nifedipine, verapamil, and diltiazem. Relevant case reports, open trials, and controlled studies reporting on the efficacy of calcium-channel blockers for treating TD are reviewed. Appropriate conclusions are drawn from the data and guidelines are suggested for the practitioner. Studies addressing the efficacy of calcium-channel blockers in the palliative treatment of TD have yielded mixed results. Positive findings have been reported for nifedipine, verapamil, and diltiazem; nifedipine may be the most efficacious treatment and diltiazem the least. It appears that patients with TD who can tolerate higher doses of calcium-channel blockers may respond more favorably to treatment. Patient characteristics that may help determine a better response to treatment with calcium-channel blockers include advanced age and more-severe TD. To determine the efficacy of calcium-channel blockers in the treatment of TD, additional data are needed from double-blind, placebo-controlled studies with larger sample sizes and longer durations of treatment. Until these data are available, calcium-channel blockers should be considered potentially useful therapy for the heretofore unresponsive TD.


Enhanced photocatalytic activities of facile auto-combustion synthesized ZnO nanoparticles for wastewater treatment: An impact of Ni doping.
In the current work, we present the facile one-pot synthesis of 0.0, 0.5, 1.0, 2.0 and 3.0 wt% of Ni doped ZnO nanoparticles (Ni:ZnO NPs) through combustion route at 550 °C. Structural and vibrational studies approve the synthesis of monophasic hexagonal Ni:ZnO NPs. The crystallite size was calculated to be in the range of 36-60 nm for pure and doped samples. The composition of all elements in the final product along with their homogeneity, was approved through EDX/FESEM e-mapping analysis. The morphology and phase confirmation of the prepared samples was investigated through FESEM and TEM/HRTEM analyses. TEM/HRTEM study shows that the size of grains is within the range of 100 nm and grown along the c-axis as the lattice spacing is found ∼2.6005 Å. Diffused reflectance study was used to estimate the energy gap for all samples and found to reduce from 3.287 eV for pure to 3.258 eV for 3.0 wt% Ni doping. From an applications point of view, the photocatalytic performance of Ni:ZnO NPs was studied, and with 3.0 wt% of Ni doping in ZnO the degradation of methylene blue (MB) and tetracycline (TCN) pollutants were found to be remarkably improved.


The Tn10-encoded tetR mRNA has heterogeneous 5' ends in vivo and in vitro.
The 5' ends of the Tn10-encoded mRNAs have been analyzed by quantitative primer extensions of the in vivo synthesized RNA and in vitro run-off transcription. The gene is transcribed by a tandem promoter system consisting of PR1 and PR2. While PR1 contributes about 25% of the total PR activity in vitro, more than 95% of the in vivo-produced transcripts originate from PR2. Transcription from PR2 shows extensive heterogeneity at the 5' ends of the mRNAs in vitro and most likely also in vivo. A deletional and oligodeoxyribonucleotide-directed mutational analysis of the PR2 transcript reveals that length heterogeneity results from reiterative copying of a run of five A's at the transcription start point. In vivo transcription leads to longer reiteration products than in vitro transcription.


Re-evaluation of over-the-counter histamine H1-receptor antagonists based on their effects on murine models of allergen-induced nasal hyperresponsiveness.
T cells play an essential role in the development of allergen-induced nasal hyperresponsiveness (NHR), a pathophysiological response in allergic rhinitis. The effects of histamine H1-receptor antagonists (antihistamines) on murine NHR models were investigated. Intragastric epinastine, fexofenadine, and loratadine administration suppressed allergen-induced immediate nasal response but not NHR in immunized mice. Regardless of the alleviation of stimulation-induced Th2 cytokine expression by loratadine and desloratadine in vitro, allergen-induced NHR and nasal eosinophil infiltration in Th2 cell-transferred mice were unaffected by loratadine in vivo. This influence on T cell-mediated NHR was excluded from the pharmacological effects of antihistamines.


SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges.
Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these - alpha and delta - subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.


Effect of lithium carbonate on subchondral bone in sexually mature Wistar rats.
Clinical and experimental studies have shown that lithium carbonate causes a number of clinical manifestations such as hyperparathyroidism, hypothyroidism, renal toxicity, and diabetes insipidus. The effect of this drug on the bone biology of experimental animals has not been studied to date. Therefore, the aim of the present experimental work was to study the effect of lithium on bone tissue in healthy sexually mature Wistar rats. Ten female Wistar rats, aged 312-412 months, 210-220 g body weight, were assigned to one of the following groups: untreated control group and experimental group receiving 45 mg/kg body weight/day of lithium carbonate in their drinking water during 3 months. Prior to euthanasia, blood samples were obtained in order to determine plasma phosphorus, calcium alkaline phosphatase, and lithium. After sacrifice, the tibiae were resected, processed, and embedded in paraffin. The following histomorphometric parameters were determined on digital photographs of the histologic sections: BV/TV (%), bone volume; Tb.Th (microm), trabecular thickness; Tb.N (mm(-2)/mm), trabecular number; Tb.Sp (microm), trabecular separation; Ob.S/BS (%), osteoblast surface; ES/BS (%), total erosive surface; Lc.S (%), lining cells surface; and GPC.Th (microm), thickness of growth plate cartilage. The results showed that administration of lithium carbonate cause bone loss in healthy sexually mature Wistar rats. Although the mechanism involved in bone toxicity remains to be clarified, the results obtained in the present study suggest that patients under long-term lithium therapy should be thoroughly evaluated, particularly those presenting other risk factors of osteopenia, such as menopause, low calcium intake, alcohol consumption, and glucocorticoid therapy.


Effect of maternal age curve on the predicted detection rate in maternal serum screening for Down syndrome.
The effect of the choice of maternal age-specific prevalence curve on the model predicted Down syndrome detection rate was examined. All 19 published regression curves from 11 birth prevalence series in four meta-analyses were included. The detection rate for a five per cent false-positive rate was estimated for three combinations of markers. For free beta human chorionic gonadotropin and alpha-fetoprotein the lowest predicted detection rate was 62.3 per cent and the highest 64.1 per cent, a range of 1.8 per cent. When unconjugated oestriol was added as a third marker it was 65.6-67.3 per cent, a 1.7 per cent range, and when inhibin A was the fourth marker the detection rate was 72.0-73.4 per cent, a 1.4 per cent range. The number of series included in the regression had the biggest effect: when the authors had used a subset thought to have the highest ascertainment the predicted detection rate generally increased. The type of regression equation used and restrictions on the age range over which the regression was performed were less important factors. The effect of the choice of curve on the predicted increase in detection achieved by incorporating additional markers was relatively small: 3.1-3.3 per cent for unconjugated oestriol and a further 6.1-6.5 per cent for inhibin A. This analysis shows that the model inaccuracy caused by the maternal age curve is not small but is unlikely to be large enough to influence Down syndrome screening policy decisions.


Advanced detector signal acquisition and electron beam scanning for high resolution SEM imaging.
The advancement of materials science at the mesoscale requires improvements in both sampling volumes/areas and spatial resolution in order to make statistically significant measurements of microstructures that influence higher-order material properties, such as fatigue and fracture. Therefore, SEM-based techniques have become desirable due to improvements in imaging resolution, large sample handling capability, and flexibility for in-situ instrumentation. By using fast sampling of SEM electron detector signals, intrinsic beam scanning defects have been identified that are related to the response time of the SEM electron beam deflectors and electron detectors. Mitigation of these beam scanning defects using detector sampling approaches and an adaptive model for settling time is shown to produce higher resolution SEM images, at faster image acquisition times, with a means to quantify the different response functions for various beam deflectors and detectors including those for electrons and ions.


"Differentiation Induction" culture of human leukemic myeloid cells stimulates high production of macrophage differentiation inducing factor.
A suitable procedure for the production of human monokines was defined as 'differentiation-induction' culture. Human monocytic leukemia THP-1 cells were well-differentiated from nonfunctional promonocytes into macrophage-like cells by the induction with a combination of mezerein, retinoic acid, and aMycoplasma fermentans extract. The differentiated THP-1 cells secreted a high amount of macrophage differentiation-inducing factor (DIF) activity and concomitantly produced other known monokines, such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β), into the medium. These results suggest that other novel human monokines may also be found in the conditioned medium of THP-1 cells induced by the 'differentiation-induction' culture conditions defined in this study. Macrophage DIF was purified to homogeneity and NH(2)-terminal amino acid sequence analysis revealed that macrophage DIF is very similar or identical to human leukemia inhibitory factor (LIF). The cDNA encoding human LIF was isolated using the polymerase chain reaction, and a clone producing 3.7 μg/10(6) cells day recombinant LIF was selected from Chinese hamster ovary (CHO) cells which were transfected with the LIF cDNA. The recombinant LIF production in CHO cells was quantified using MTT reduction assay with M1 cells.


Mesenteric Ischemia: A Deadly Miss.
Mesenteric ischemia has 4 etiologies: arterial embolus, arterial thrombosis, venous thrombosis, and nonocclusive. No history or physical examination finding can definitively diagnose the condition. A wide variety of presentations occur. Pain out of proportion and gut emptying may occur early, with minimal tenderness. Once transmural infarction occurs, peritoneal findings and tenderness to palpation may occur. Physicians must be suspicious of pain out of proportion and scrutinize risk factors. Computed tomography angiography is the best imaging modality. Treatment requires surgery and interventional radiology consultation, intravenous antibiotics and fluids, and anticoagulation. The physician at the bedside is the best diagnostic tool.


Pelvic lymph node metastasis of uterine cervical cancer.
The state of pelvic lymph node metastasis was observed in 627 cases of Okabayashi's radical hysterectomy performed from 1950 to 1984 of which 589 cases with a known 5-year survival rate were examined according to their relationship to prognosis. The incidence of lymph node metastasis was 29.7%, becoming progressively higher with succeeding clinical stages. The metastasis rates according to site were 6.9% hypogastric nodes, 4.9% obturator nodes, 4.4% iliac nodes, and 25.0% parametrial nodes. Among the factors considered in the postoperative classification, lymph node metastasis demonstrated high values in cervical infiltration cancer, positive parametrial infiltration, positive vaginal invasion, and infiltration into the uterine body and L type of CPL classification. The 5-year survival rate was 83.0% in negative cases of pelvic lymph node metastasis, while in positive cases, it was as poor as 45.8%. Considering the relationship of various factors, it is shown that the presence of lymph node metastasis has a great effect on prognosis.


Two ankle joint laxity testers: reliability and validity.
Two test devices were manufactured to objectively measure ankle joint laxity: the dynamic anterior ankle tester (DAAT) and the quasi-static anterior ankle tester (QAAT). The primary aim was to analyse the reliability of both testers; The secondary aim was to assess validity in correlation with TELOS stress test and manual anterior drawer test. Twenty-four normal subjects and 14 patients 1 year after acute lateral ankle ligament injury were included. Both ankles were tested with the DAAT and QAAT by two different observers; one experienced orthopaedic surgeon performed the manual test; the TELOS stress X-rays were evaluated by one observer. Intra observer reliability for the DAAT varied between 0.81 and 0.94; for the QAAT between 0.71 and 0.94. Inter observer reliability for the DAAT varied between 0.84 and 0.94; for the QAAT between 0.76 and 0.82. Concurrent validity showed fair correlation between DAAT and QAAT for the first couple observers (0.71); however, a poor correlation was observed for the second couple (0.42). No significant correlations were found between neither DAAT and the TELOS and the manual test, nor QAAT and the TELOS and the manual test. In conclusion, reliability of both testers is high. Validity of the testers needs further investigation.


An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes.
Postprandial hyperglycemia is known to be one of the earliest signs of abnormal glucose homeostasis associated with type 2 diabetes. This study aimed to assess clinical significance of a 1-h postprandial glucose level for the development of diabetes, and identify epigenetic biomarkers of postprandial hyperglycemia. We analyzed clinical data from the oral glucose tolerance tests for healthy subjects (n=4502). The ratio (Glu60/Glu0) of 1-h glucose levels to fasting glucose levels was significantly associated with an insulin sensitive index (QUICKI, quantitative insulin sensitivity check index) (β=0.055, P=1.25E-04) as well as a risk of future pre-diabetic and diabetic conversion. Next, DNA methylation profile analyses of 24 matched pairs of the high and low Glu60/Glu0 ratio subjects showed that specific DNA methylation levels in the promoter region of an olfactory receptor gene (olfactory receptor gene family10 member A4, OR10A4) were associated with the Glu60/Glu0 ratios (β=0.337, P=0.03). Moreover, acute oral glucose challenges decreased the DNA methylation levels of OR10A4 but not the global DNA methylation in peripheral leukocytes of healthy subjects (n=7), indicating that OR10A4 is a specific epigenomic target of postprandial hyperglycemia. This work suggests possible relevance of olfactory receptor genes to an earlier molecular biomarker of peripheral hyperglycemia and diabetic conversion.


Aging potentiates Abeta-induced depletion of SNAP-25 in mouse hippocampus.
Previously we showed that in Tg2576 mouse hippocampus, synaptosomal-associated protein 25 (SNAP-25) immunoreactivity (IR) is greatly reduced and intracerebroventricular injection of anti-Abeta reverses this depletion. 3- and 24-month-old wild-type mice received juxta-amygdala injection of Abeta42 and hippocampal sections were analyzed for glial fibrillary acidic protein (GFAP)- and SNAP-25-IR at intervals after injections. In young mice, SNAP-IR declined >95% at 1 week in DG-Smi and remained low until 8 weeks, while decreasing in SR, SL and hilum by 8-27% at 1 week and returning to baseline by 2 weeks. There was no change in DG-SMm. In old mice, DG-Smi was specifically depleted in SNAP-IR by >95% even before injection. At 2 weeks, SNAP-IR had declined in all layers by 30-39% of baseline values and by 8 weeks had returned to control values, except the DG-SMm which showed only a 10% reduction at 2 weeks. Baseline GFAP-IR was 10-fold higher in old than in young mice in the fimbria/IC but not appreciably changed in hippocampus. In young mice, the injections of Abeta caused 20-fold increases in GFAP-IR in the fimbria/IC and 2-fold increases in the hippocampal neuropil at 1 week, all of which values returned to baseline by 8 weeks. In old mice, Abeta injections caused relatively much larger increases in GFAP-IR in the hippocampal neuropil than in the fimbria/IC and the GFAP-IR remained greatly increased at 8 weeks. the Abeta effect on presynaptic SNAP-25 depletion is increased with age. DG-SMi shows the most severe changes and therefore may represent the most critical site in hippocampus for Abeta neurotoxicity.


Mutagenicity of trichloroethylene, trichloroethanol and chloral hydrate in Aspergillus nidulans.
A trichloroethylene (TCE) sample, free of epoxides, has been assayed for its ability to induce gene mutations (methionine suppressors) and mitotic segregation in the mould Aspergillus nidulans. No increase in the spontaneous frequency of methionine suppressors was observed when conidia of a haploid strain were plated on selective medium and exposed to TCE vapours. A weak but statistically significant increase in methionine suppressors was detected, however, when conidia of cultures grown and conidiated in the presence of TCE vapours were plated onto selective media. Growing colonies of a heterozygous diploid strain were exposed to TCE vapours to investigate the induction of mitotic segregation. Scoring and phenotypic analysis of segregant sectors showed a significant increase in the frequency of haploids and 'non-disjunctional' diploids but not of cross-overs. Treatment of quiescent conidia in liquid medium was ineffective. Trichloroethanol and chloral hydrate, two main TCE metabolites in mammals, shared the ability to induce somatic segregation demonstrated by TCE vapours. On the grounds of these results the possible endogenous metabolic conversion of TCE into trichloroethanol and chloral hydrate is hypothesized.


Lessons from a national audit of acute pancreatitis: A summary of the NCEPOD report 'Treat the Cause'.
The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) is an independent organisation whose remit is to review the quality of medical and surgical care provided in the United Kingdom. We undertook a review into the care provided to patients treated for acute pancreatitis during a 6 month study period between 1st January and 30th June 2014. This included assessment of care at an organisational level, clinical level within hospitals and external peer review. From a random sample, 712 patients underwent hospital clinician review and 418 patients had external peer review. Overall, we found that there was room for improvement in care in over 50% of patients with acute pancreatitis. Case reviewers felt that efforts to prevent recurrent episodes due to gallstones and alcohol were inadequate as 21% of patients in the study had one or more previous episodes of acute pancreatitis. Aspects of general care where improvements could be made include better antibiotic stewardship; as 1/5 of patients were considered to have been given antibiotics unnecessarily. Overall management of the patients' nutrition was considered adequate by the case reviewers in only 85% of cases. The use of an early warning score was omitted in 31% of emergency department admissions. Recommendations include standardised early warning scoring systems to be used throughout the hospital and commenced in the emergency department. The development of better networking arrangements and regional pancreatitis units, with shared management guidelines, is also essential to improve the coordination of care.


Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI.
F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL. Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests. Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI). Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.


Birt-Hogg-Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome.
Birt-Hogg-Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt-Hogg-Dubé syndrome patients. The folliculin gene (FLCN) that is responsible for Birt-Hogg-Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer.


1-[5-(3,5-Di-meth-oxy-phen-yl)-3-(2-meth-oxy-phen-yl)-4,5-di-hydro-1H-pyrazol-1-yl]ethanone.
In the title compound, C20H22N2O4, two benzene rings bearing meth-oxy substituents are connected by a central acetyl-pyrazoline ring: the dihedral angle between the benzene rings is 83.7 (1)°. In the crystal, pairwise C-H⋯O hydrogen bonds generate inversion dimers and additional weak C-H⋯O inter-actions link the dimers into chains propagating along the c-axis direction.


A complex pattern of disposition of phenytoin in severe intoxication.
A 5-year-old child developed phenytoin (diphenylhydantoin, DPH) toxicity after receiving 500 mg of the drug daily for 3 weeks. Plasma, urine, and duodenal fluid were collected for assay of DPH and its metabolites. The peak plasma concentration of DPH was 108 mug/ml, and the decline in plasma level did not fit first-order kinetics. The para-hydroxy, meta-hydroxy, and dihydrodiol metabolites of DPH were measured in urine; duodenal aspirate contained both DPH and the para-hydroxy metabolite. Plasma pH may affect distribution of DPH since in vitro binding of DPH to human albumin increased as pH increased.


Classification and management of epilepsy and epileptic syndromes in a cohort of 202 school children- a 2 year follow up study- Sudan.
In this paper, seizure types, and epilepsy syndromes are elucidated as per ILAE (2010) classification. A brief outline of the antiepileptic drug regimens used and the outcome of seizure control in a two -year period is presented. The applicability of the ILAE classification in resource limited countries has been revisited. This is a descriptive prospective study, in which 202 patients were enrolled. The Cohort group was seen and evaluated by a pediatric neurologist at the Pediatric neurology Outpatients Department (OPD). Epilepsy was classified using the International League Against Epilepsy (ILAE) classification (2005-2009) report. All patients had an Electroencephalogram (EEG) at the start of the study, and this was repeated as deemed appropriate. Brain imaging (MRI) was done to patients when indicated. Treatment decisions were made by pediatric neurologists. Outcomes were categorized into four groups: fully recovered, well controlled, partially controlled and uncontrolled. The mean age is 10.5 + 2.7 years. Male to female ratio was 1.7: 1. Thirty five (17.3%) patients had generalized onset seizures, 46(22.8%) had focal onset seizures, 104(51.5%) had a specific epilepsy syndrome, and 17(8.4%) patients were unclassified. 170 (84.2%) patients were on mono-therapy on their initial visit, 30(14.8%) were on two Antiepileptic Drugs (AEDs) while two (1.0%) patients were on poly-therapy. After 2 years; 155(76.7%) patients were on mono-therapy, 36(17.8%) on two AEDs while ten were (4.0%) on polytherapy. One eighty (88.2%) patients were controlled. Fifteen (7.4%) of them were off medication after being seizure free for 2 years. Twenty (9.8%) have partial control, while two (1.0%) patients were uncontrolled. Patients with focal epilepsy, those on polytherapy and those with abnormal imaging had poor prognosis. The ILAE classification can be used in resource limited countries. Childhood epilepsies have a good prognosis provided they are well classified and treated.


From beef to beans: Eating motives and the replacement of animal proteins with plant proteins among Finnish consumers.
A better understanding of the motives underlying the adoption of sustainable and healthy diets is needed for designing more effective policies. The aim of the study was to examine how eating motives were associated with self-reported changes in the consumption of beef, beans, and soy products, i.e., changes related to reducing animal and increasing plant proteins. The study analysed a survey of an adult population living in Finland (N = 1048). The eating motives were measured with the Eating Motivation Survey (TEMS), which distinguishes between 15 eating motives. Six clusters of consumers based on self-reported changes in food choices were identified with latent class analysis (LCA). Four clusters had established food consumption patterns ("Beef only", "Beef and beans", "Beef, beans, and soy products", and "No beef"), one was undergoing a change, and one had attempted a change earlier. ANOVA with planned contrasts revealed that the motives relating to natural concerns, health, and weight control were higher, and convenience and price lower, among those who had an established diet including beans and soy products, as compared to those who consumed only beef. Those undergoing a dietary change expressed a higher endorsement of natural concerns as well as health, sociability, social image, and price motives than those with an established diet including beans and soy products. The results suggest that eating motives play an important role in changing towards more sustainable food consumption patterns in which meat/beef is replaced with plant proteins.


Interspecific actions of alpha mating pheromones on the a mating-type cells of three Saccharomyces yeasts.
The alpha mating pheromones synthesized in three Saccharomyces yeasts (S. cerevisiae, S. kluyveri, and S. exiguus) displayed interspecific actions on the a cells of all three species despite the fact that the amino acid sequences of all three alpha pheromones are different. Mating between species, however, did not occur. The interspecific alpha pheromone--a cell reaction was not necessarily more effective than the interspecific one.


Oxygen and temperature affect cell sizes differently among tissues and between sexes of Drosophila melanogaster.
Spatio-temporal gradients in thermal and oxygen conditions trigger evolutionary and developmental responses in ectotherms' body size and cell size, which are commonly interpreted as adaptive. However, the evidence for cell-size responses is fragmentary, as cell size is typically assessed in single tissues. In a laboratory experiment, we raised genotypes of Drosophila melanogaster at all combinations of two temperatures (16 °C or 25 °C) and two oxygen levels (10% or 22%) and measured body size and the sizes of cells in different tissues. For each sex, we measured epidermal cells in a wing and a leg and ommatidial cells of an eye. For males, we also measured epithelial cells of a Malpighian tubule and muscle cells of a flight muscle. On average, females emerged at a larger body size than did males, having larger cells in all tissues. Flies of either sex emerged at a smaller body size when raised under warm or hypoxic conditions. Development at 25 °C resulted in smaller cells in most tissues. Development under hypoxia resulted in smaller cells in some tissues, especially among females. Altogether, our results show thermal and oxygen conditions trigger shifts in adult size, coupled with the systemic orchestration of cell sizes throughout the body of a fly. The nature of these patterns supports a model in which an ectotherm adjusts its life-history traits and cellular composition to prevent severe hypoxia at the cellular level. However, our results revealed some inconsistencies linked to sex, cell type, and environmental parameters, which suggest caution in translating information obtained for single type of cells to the organism as a whole.


Pattern strabismus in consecutive esodeviation after bilateral lateral rectus muscle recession for intermittent exotropia.
After bilateral lateral rectus recession for intermittent exotropia, children can develop V- or A-pattern esodeviation and adopt a chin-down or chin-up position to facilitate fusion. The aim of this study was to discuss possible causes and management of this pattern. The medical records of children who developed consecutive esodeviation with V- or A-pattern strabismus after surgery for intermittent exotropia but with no pre- or postoperative oblique muscle dysfunction were reviewed retrospectively. Ductions, versions, angles of deviation, and fundus torsion were evaluated before and after surgery. Patient management and outcomes were analyzed. A total of 37 patients were identified (mean age, 5.7 ± 1.5 years), with a mean preoperative deviation of 30.6Δ ± 5.2Δ; no patient had a preoperative pattern strabismus. Mean bilateral lateral rectus recession was 6.2 ± 0.9 mm. Of the 37, 34 (89%) returned postoperatively with V pattern, 2 with an A pattern, and 1 with an hourglass-like pattern. No patient showed oblique muscle dysfunction or fundus torsion. Reoperation for the consecutive deviation was performed in 19 patients, in all of whom the lateral rectus muscles were not vertically displaced. The pattern disappeared completely after reoperation and reestablishment of adequate alignment in the primary position. In our patient cohort, pattern strabismus after bilateral lateral rectus recession was successfully reversed by correction of the consecutive esodeviation.


The professional resilience of mid-career GPs in the UK: a qualitative study.
With a continued crisis of increasing workload and reduced workforce in general practice, supporting resilience is a key strategy for sustaining the profession into the future. How do GPs perceive professional resilience, and what workplace factors influence it? A UK-based qualitative study of the perspectives of GPs currently practicing in mainly urban locations across the UK with ≥5 years' experience after completion of GP training. Participants were recruited using convenience sampling, which included social media forums, and underwent semi-structured interviews undertaken in May and June 2020 (n = 27). Data were analysed using thematic analysis. Participants offered definitions of and influences on resilience that largely fit with existing research, but in addition, may result in the perception that GPs are obstructive, or that resilience may be a 'surface act'. GPs agree that the current focus on methods of improving resilience does support them, but there is significantly more to be done in this field. Social media activity aiming at GP support may be counterproductive. Reduction of clinical working hours is a common strategy to improve resilience. That GPs feel to improve resilience they need to work fewer clinical hours may have huge implications for a workforce already in crisis, and ultimately, for the health care of the UK population. Urgent research is needed to formulate a bespoke assessment for measuring GP resilience to assess potential interventions, and to identify GPs at risk of mental ill-health or leaving the profession.


[Infantile fibrosarcoma mimicking rapidly involuting congenital haemangioma (RICH)].
While haemangioma is common, an unusual appearance or course should alert the clinician's concern. Congenital haemangioma, particularly rapidly involuting congenital haemangioma (RICH), may carry a risk of misdiagnosis as congenital malignant tumours such as infantile fibrosarcoma (also known as congenital infantile fibrosarcoma). In this case, histological diagnosis may prove inconclusive, as in the case reported herein. At birth, a newborn baby presented angiomatous lesions on the sole of the left foot that was initially considered as congenital haemangioma. Histopathological examination suggested highly remodelled immature infantile haemangioma. After surgery, the tumour increased in size within eight weeks. Reanalysis of the histology slides resulted in a diagnosis of infantile fibrosarcoma. This diagnosis was confirmed by the presence of a specific translocation seen in infantile fibrosarcoma (ETV6/NTRK3). There is a risk of erroneous diagnosis in newborn infants between angiomatous tumour in RICH and malignant congenital tumours (particularly infantile fibrosarcoma). Clinicians should be attentive for this type of lesion and take all necessary diagnostic measures.


The clinical impact of preoperative percutaneous drainage of abdominopelvic abscesses in patients with Crohn's disease.
Although image-guided percutaneous drainage is increasingly being used to treat Crohn's disease-related abdominopelvic abscesses, surgery is seldom avoided. The aim of this study was to compare outcomes following the treatment of intra-abdominal Crohn's abscesses with percutaneous drainage followed by surgery to those after surgery alone. We retrospectively reviewed the charts of patients treated for Crohn's-related abdominopelvic abscesses at Mount Sinai Medical Center between April 2001 and June 2010. Patients who underwent drainage followed by surgery were compared to those who underwent surgery alone. Differences in operative and postoperative outcomes were compared. Seventy patients with Crohn's disease-related abdominopelvic abscesses were identified, 38 (54%) of whom underwent drainage before surgery. Percutaneous drainage was technically successful in 92% of patients and clinically successful in 74% of patients. No differences in rate of septic complications (p = 0.14) or need for stoma creation (p = 0.78) were found. Patients who underwent percutaneous drainage had greater overall hospital lengths of stay (mean 15.8 versus 12.2 days, p = 0.007); 8.6% of patients had long-term postponement of surgery after percutaneous drainage. In our series, the treatment of Crohn's abscesses with percutaneous drainage prior to surgery did not decrease the rate of postoperative septic complications.


Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake.
Nitrogen balance at three levels of protein intake was measured in eight patients with cirrhosis of the liver; moreover, at each level of protein intake, the effects on nitrogen balance of branched-chain amino-acid enriched protein and natural protein were compared. From these nitrogen balance data, minimum protein requirements were calculated by linear regression analysis. The patients were in a negative nitrogen balance on a 40 g protein diet (-0.75 +/- 0.15 gN.), and in positive nitrogen balance on 60 g (+1.23 +/- 0.22 gN.) or 80 g of protein per day (+2.77 +/- 0.20 g N.). Their mean minimum protein requirement (48 +/- 5 g of protein/day or 0.75 g/kg/day) is higher than expected in healthy people; the safe level of protein intake (mean + 2 sd) is 58 g per day or 1.2 g/kg/day. Nitrogen balances and protein requirements were not different on branched-chain amino-acid enriched diets. The physical condition of the patients improved when they came into positive nitrogen balance; the higher rates of protein intake were well tolerated without onset of encephalopathy. We conclude that protein requirements are elevated in cirrhosis of the liver; diets supplying less than 60 g of protein per day should not be prescribed in long term treatment of cirrhotic patients.


The prevalence extent of Complementary and Alternative Medicine (CAM) use among Saudis.
Introduction: There is worldwide interest in the use of CAM. Studying CAM in Saudi population is important as it will reflect the influence of psychosocial, cultural and religious factors on health beliefs and behaviors. The objective of this study was to present an updated review on the use of CAM practices in Saudi Arabia including commonly used types, common conditions for which it has been used and who uses CAM. Methods: This review used data from national surveys conducted in Saudi Arabia and published between 2000 and 2015. The literature search was performed considering standards adopted such as Moose guidelines for observational studies. Two authors independently reviewed each article. The search yielded 73 articles, and a total of 36 articles were included. Further careful data extraction was carried out by two independents reviewers. Results: Most of the reviewed studies were cross-sectional in design and were published between 2014 and 2015, and mostly in Riyadh region. Substantial difference in the findings for the patterns of CAM use was revealed. The most commonly employed practice was of spiritual type such as prayer and reciting Quran alone or on water. Other types include herbs (8-76%), honey (14-73%) and dietary products (6-82%). Cupping (Alhijamah) was least used (4-45%). Acupuncture was more practiced among professionals. Conclusion: The utilization of CAM is widely practiced in Saudi Arabia. There is need for efforts to promote research in the field of CAM to address each practice individually. Population surveys should be encouraged supported by mass media to raise knowledge and awareness about the practice of different CAM modalities. The national center of CAM should play a major role in these efforts.


Courtship behavior of Zaprionus indianus (Gupta) (Diptera: Drosophilidae) from populations colonizing South America.
We describe for the first time the sexual behavior and the courtship song of males of the African fly Zaprionus indianus (Gupta), a recent invader of South America. The male courtship song is formed by monocyclic pulses and the courtship behavior is simple when compared to that of species of Drosophila. Two interpulse interval (IPI) distributions were observed: pre-mounting and mounting. No significant difference was observed between the pre-mounting IPIs of males that descended from three geographical populations from South America. We also observed the songs produced by females and the homosexual behavior exhibited by males. A sequence of bursts is produced by females as a refusal signal against males, while males emit a characteristic song that identifies sex genus, which differs from the courtship song. The short courtship and mating latencies recorded reveal vigorous males and receptive females, respectively.


[Effect of Pinus massoniana needle extract on root dentin demineralization in vitro].
This study aims to evaluate the effects of Pinus massoniana needle extract (PMNE) on inhibiting demineralization of root dentin. Root dentin blocks were randomly divided into distilled deionized water (DDW) group, fluoride sodium (NaF) group, and 4%, 8% and 12% PMNE groups according to the experimental solution used in the process of pH cycling in each group. All specimens in each group experienced pH cycling for 8 d. The dentin mineral density (DMD) of the normal dentin and demineralized dentin and their D-value (ΔDMD) were determined using micro computed tomography. The morphology of dentin surface after pH cycling was also observed using a scanning electron microscope. The ΔDMD values in all PMNE groups and the NaF group were considerably lower than the ΔDMD in the DDW group (P<0.05). The ΔDMD values of the 8% and 12% PMNE groups had no difference (P>0.05), both of which were lower than the ΔDMD in the 4% PMNE group and higher than that in the NaF group (P<0.05). The dentin tubules were partly opened in the PMNE groups. The opening degrees of the dentin tubule in PMNE groups were significantly less and smaller than the opening degree in the DDW group and were larger than that in the NaF group. PMNE can inhibit the deminera-lization of root dentin and can slow down the reduction in DMD. PMNE has the potential to prevent caries, and 8% PMNE can effectively inhibit dentin demineralization.


Effects of number of alternatives on the psychological refractoriness of an extended movement .
The single-channel prediction that delays in RT2 should be proportional to RT1 was examined by varying the number of alternatives (one, two, or three) in the primary response which was an extended arm swing at maximal speed. The second response was a thumb key release. Foreperiods were 2, 3, or 4 sec., and interstimulus intervals (ISIs) ranged from .10:50 sec. in .10-sec. steps. General support for the single-channel model was found in that RT2 paralleled changes in RT1. However, RT2 was greater than predicted when the second signal (S2) occurred during the execution of the primary response. In addition, while delays in RT2 as a function of ISI - RT1 showed corresponding differences between choice conditions, most values were greater than predicted. The deviations from the single-channel model appeared to be explained best in terms of a decrease in readiness to respond to the second signal as ISI lengthened.


Rapid estimation of readily leachable triazine residues in soils using automatic kinetic bioaccessibility assays followed by on-line sorptive clean-up as a front-end to liquid chromatography.
An automatic batchwise bioaccessibility test was proposed for on-line monitoring of readily mobile pools of ametryn and atrazine residues in agricultural soils with different physicochemical properties. A 0.01molL(-1) CaCl2 solution mimicking rainwater percolation through the soil profiles was used for the herbicide extractions. The extract aliquots were successively sampled at regular time intervals in order to investigate the extraction kinetics. For extract clean-up and retention of freely dissolved target species, 30mg of restricted-access like copolymer were used as in-line sorptive material followed by elution with methanol and on-line heart-cut injection towards a C18 silica reversed-phase monolithic column (100×4.6mm) in a liquid chromatographic system. A mathematical model emphasized that the readily available pools vs time can be in most instances described by a first-order exponential equation, thus an asymptotical value is approached. Consequently, the leaching assays can be performed without attaining chemical equilibrium. Enhancement factors and detection limits were 10.2 and 18.8, and 0.40 and 0.37mgkg(-1) for ametryn and atrazine, respectively. The automatic method features good repeatability for leaching tests (r.s.d.: 11.8-10.2% for sandy and 3.7-6.2% for clayey soil). Reliable data, demonstrated with relative recoveries in the soil leachates ranging from 86 to 104%, were achieved in less than 35min, thus avoiding the need for up to 24h as recommended by standard leaching methods.


[Research on chemical constituents of xuefu zhuyu decoction].
To investigate the chemical constituents of Xufu Zhuyu decoction. Silica gel column chromatography, Sephadex LH-20 chromatography and crystallization were employed for the isolation and purification. The structures were elucidated by physicochemical properties and spectral analysis. Eleven compounds were isolated and identified as follows: palmitic acid (1), stearic acid (2), beta-sitosterol (3), oleanolic acid (4), pregnenolone (5), tangeratin (6), 4-hydroxy-3-butylphthalide (7), sorhamnetin (8), friedelinol (9), beta-ecdysone (10), ferulic acid (11). All these compounds are isolated from Xuefu Zhuyu decoction for the first time.


Cartilaginous tumors and chordomas of the cranial base.
Chordomas and chondrosarcomas are uncommon skull base tumors. They are locally aggressive. Chordomas arise from the clivus with the epicenter in the midline of the skull base. Chondrosarcomas, in contrast, usually arise along the petro-occipital fissure; occasionally, a chondrosarcoma may reveal a midline location and then cannot be differentiated from chordoma. Chordomas rarely calcify, whereas calcification is not an uncommon finding in chondrosarcomas. Following radiation, calcifications also increase in area and diameter in both chondrosarcomas. Both chondrosarcomas and chordomas reveal a low signal intensity on T1-weighted MR images and medium to increased signal intensity on T2-weighted images. They commonly enhance significantly but heterogeneously, because of the presence of necrosis, calcification, and mucinous materials. Occasionally, chondrosarcomas and chordomas reveal a low degree if enhancement. The prognoses of chordomas and chondrosarcomas vary. Long-term survival is usually seen with chondrosarcomas but is still considerably compromised with chordomas.


Impact of visitors and hospital staff on nosocomial transmission and spread to community.
We develop a deterministic meta-population model to qualitatively capture some key features of disease transmission between a community and its healthcare facility. We consider the disease transmission dynamics within a healthcare facility and between the healthcare facility and its community. The focus of this study is to quantify the roles of the healthcare workers at and visitors to this healthcare facility in shaping the transmission dynamics during a disease outbreak. We stratify the total population into the general population in the community and the healthcare workers and visitors in the healthcare facility, to account for nosocomial transmission in the case when an individual in the community may be exposed to an infection due to a visit to the healthcare facility. Equilibrium stability analysis is carried out to inform long-term outcomes of disease dynamics in the coupled community-health care facility system. The basic reproduction number is calculated and its dependence on the waiting time and various disease transmission rates is analyzed. Numerical simulations are performed with pertussis as the disease in question. The results show that waiting time only affects the peak number of infections in the waiting reception area. The results also indicate that transmission rate of infective residents in the community and the transmission rate of the infective visitors at the healthcare facility have decisive impact on disease eradication/persistence of the coupled system; while other modes of transmissions are less important, affecting the peak number of infections at best.


A new non-human primate model of desiccating stress-induced dry eye disease.
Dry eye disease (DED), a multifactorial ocular surface disease, is estimated to affect up to 34% of individuals over 50 years old. Although numerous animal models, including rodents and rabbits, have been developed to mimic the pathophysiologic mechanisms involved in dry eye, there is a lack of non-human primate (NHP) models, critical for translational drug studies. Here, we developed a novel desiccating stress-induced dry eye disease model using Rhesus macaque monkeys. The monkeys were housed in a controlled environment room for 21 to 36 days under humidity, temperature, and airflow regulation. Following desiccating stress, NHPs demonstrated clinical symptoms similar to those of humans, as shown by increased corneal fluorescein staining (CFS) and decreased tear-film breakup time (TFBUT). Moreover, corticosteroid treatment significantly reduced CFS scoring, restored TFBUT, and prevented upregulation of tear proinflammatory cytokines as observed in dry eye patients following steroid treatment. The close resemblance of clinical symptoms and treatment responses to those of human DED patients provides great translational value to the NHP model, which could serve as a clinically relevant animal model to study the efficacy of new potential treatments for DED.


Immunopharmacology--antibodies for specific modulation of proteins involved in neuronal function.
The application of antibodies to living neurones has the potential to modulate function of specific proteins by virtue of their high specificity. This specificity has proven effective in determining the involvement of many proteins in neuronal function where specific agonists and antagonists do not exist, e.g. ion channel subunits. We discuss studies where antibodies modulate functions of voltage gated sodium, voltage gated potassium, voltage gated calcium hyperpolarisation activated cyclic nucleotide (HCN gated) and transient receptor potential (TRP) channels. Ligand gated channels studied in this way include nicotinic acetylcholine receptors, purinoceptors and GABA receptors. Antibodies have also helped reveal the involvement of different intracellular proteins in neuronal functions including G-proteins as well as other proteins involved in trafficking, phosphoinositide signalling and neurotransmitter release. Some suggestions for control experiments are made to help validate the method. We conclude that antibodies can be extremely valuable in determining the functions of specific proteins in living neurones in neuroscience research.


The effect of symptom duration in epithelial ovarian cancer on prognostic factors.
To assess the association between duration of symptoms and main prognostic factors of invasive epithelial ovarian cancer (EOC). The data of all histologically confirmed EOC patients diagnosed in Israel during the period 1994-1999 (n = 1,005) were retrieved from discharge summaries and admission records. Of the 371 (36.9%) patients with known presenting symptoms, the durations of 187 (50.4%) were recorded. The most common presenting symptoms were abdominal pain (65.2%). The percentage of patients with three or more symptoms increased significantly with stage (P = 0.001). No statistically significant association between duration of symptoms and prognostic factors was found. Our findings did not show an association between duration of symptoms and prognostic factors in EOC patients and may indicate that prognosis is not a function of delay in diagnosis.


Peripheral inflamation-induced increase of AMPA-mediated currents and Ca2+ transients in the presence of cyclothiazide in the rat substantia gelatinosa neurons.
This study employing a rodent model of acute pain investigated the influence of carrageenan-induced inflammation on the ability of S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation to induce membrane currents and rises in cytosolic free calcium concentration ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole-cell patch-clamp recording and fura-2 calcium imaging in spinal cord slices of L4-L5 segments. The novel finding of this study is that carrageenan-induced inflammation, in the presence of cyclothiazide, an inhibitor of AMPA receptor desensitization, produces a sustained facilitation of the AMPA-mediated membrane current and rises in [Ca2+]i in both the soma and proximal dendrites of SG neurons recorded on the injected side 3 h after the induction of inflammation. These results suggest that in carrageenan-inflamed rats AMPA receptors undergo some alterations that influence AMPA receptors desensitization and/or sensitivity to cyclothiazide.


Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.
Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.


1H NMR conformational study of sulfated and non-sulfated cholecystokinin fragment CCK27-33: influence of the sulfate group on the peptide folding.
1H NMR study of cholecystokinin fragment (CCK27-33) in (C2H3)2SO and in 2H2O at different pH shows that sulfated (CCK7) and non sulfated (NS-CCK7) peptides are under preferentially folded conformations characterized by a beta-turn including the sequence Gly-Trp-Met-Asp with a H-bond between the CO of Gly and the NH of Asp. This structure is probably stabilized by an ionic interaction between Tyr and Asp. Moreover, the N-terminal part of CCK7 forms a C7 structure with a weak H-bond between the CO of Gly and the NH of Trp. In this model all CCK7 hydrophobic side chains are in close vicinity, far from the hydrophilic sulfate group. Full interaction with brain CCK8 receptors could require both the sulfate group and the maintaining of conformational constraints.


Characterization of a dominant mutation for the liguleless trait: Aegilops tauschii liguleless (Lgt).
Leaves of Poaceae have a unique morphological feature: they consist of a proximal sheath and a distal blade separated by a ligular region. The sheath provides structural support and protects young developing leaves, whereas the main function of the blade is photosynthesis. The auricles allow the blade to tilt back for optimal photosynthesis and determine the angle of a leaf, whereas the ligule protects the stem from the entry of water, microorganisms, and pests. Liguleless variants have an upright leaf blade that wraps around the culm. Research on liguleless mutants of maize and other cereals has led to identification of genes that are involved in leaf patterning and differentiation. We characterized an induced liguleless mutant (LM) of Aegilops tauschii Coss., a donor of genome D of bread wheat Triticum aestivum L.. The liguleless phenotype of LM is under dominant monogenic control (Lgt). To determine precise position of Lgt on the Ae. tauschii genetic map, highly saturated genetic maps were constructed containing 887 single-nucleotide polymorphism (SNP) markers derived via diversity arrays technology (DArT)seq. The Lgt gene was mapped to chromosome 5DS. Taking into account coordinates of the SNP markers, flanking Lgt, on the pseudomolecule 5D, a chromosomal region that contains this gene was determined, and a list of candidate genes was identified. Morphological features of the LM phenotype suggest that Lgt participates in the control of leaf development, mainly, in leaf proximal-distal patterning, and its dominant mutation causes abnormal ligular region but does not affect reproductive development. Here we report characterization of a liguleless Ae. tauschii mutant, whose phenotype is under control of a dominant mutation of Lgt. The dominant mode of inheritance of the liguleless trait in a Triticeae species is reported for the first time. The position of the Lgt locus on chromosome 5DS allowed us to identify a list of candidate genes. This list does not contain Ae. tauschii orthologs of any well-characterized cereal genes whose mutations cause liguleless phenotypes. Thus, the characterized Lgt mutant represents a new model for further investigation of plant leaf patterning and differentiation.


Anaerobic threshold, muscle volume and hypoxia.
Ventilatory threshold, apparent mechanical efficiency, oxygen debt repayment, heart rate and perceptions of exertion at the ventilatory threshold have been examined in 8 men and 8 women during the performance of four types of exercise (2-leg, 1-leg, arm plus shoulder, and arm ergometry) under normoxic and hypoxic (12% oxygen) conditions. The ventilatory threshold (percentage of task-specific VO2peak at which a disproportionate increase of ventilation begins) was not significantly affected by the sex of the subject, by hypoxia, or by the volume of active muscle involved in the activity, but showed poor reproducibility in small muscle tasks. The apparent mechanical efficiency in 2-leg ergometry was increased from 25.7 to 28.1% under hypoxic conditions, presumably reflecting an increased contribution of anaerobic effort to sub-maximal work. However, oxygen debt repayment following exhausting exercise was much smaller for arm than for leg ergometry. The heart rate corresponding to the ventilatory threshold decreased as the volume of active muscle was reduced. General and respiratory perceptions of effort were rather light for self regulation of an exercise prescription to the ventilatory threshold, and particularly with tasks involving the arm muscles, prescription may best be regulated by the intensity of local muscular sensations.


Magnetic Resonance Imaging of Liver Fibrosis, Fat, and Iron.
Chronic liver disease (CLD) is a large and ever-growing problem in both the US and world health care systems. While histologic analysis through liver biopsy is the gold standard for hepatic parenchymal evaluation, this is not feasible in such a large population of patients or as a way of monitoring change over time. This review discusses MRI-based techniques for assessing hepatic fibrosis, hepatic steatosis, and hepatic iron content, with discussions of both current techniques and future advancements.


Drug Prescription Including Interactions with Anticancer Treatments in the Elderly: A Global Approach.
Consequences of inappropriate prescriptions and polymedication in patients suffering from cancer are beginning to be well documented. However, the methods used to evaluate these consequences are often discussed. Few studies evaluate the risk of interaction with anticancer drugs in elderly patients suffering from cancer. To describe the prevalence (i) of polypharmacy, (ii) of potentially inappropriate drug prescriptions and (iii) of drug interactions involving anticancer treatments, using a multiple reference tools. A retrospective, cross-sectional, multicenter study performed from January to December 2012. Patients aged 65 years or older suffering from cancer presented at the oncogeriatric multidisciplinary meeting. Polymedication (>6 drugs), potentially inappropriate prescriptions and drug interactions involving anticancer treatment were analyzed in combination with explicit and implicit criteria within a global approach. Among the 106 patients included in this study, polypharmacy was present in 60.4% of cases, potentially inappropriate drug prescription in 63.1% and drug interactions in 16% of case, of which 47% involved anti-cancer treatments. Twenty-seven major drug interactions were identified and eight interactions involved chemotherapy. Polymedication, inappropriate prescribing and drug interactions involving anti-cancer drugs are common and largely underestimated in elderly cancer patients.


Coprecipitation modulates the solubility of minerals in bovine milk.
The solubilities of zinc, iron, copper, magnesium, calcium, inorganic phosphate, and citrate in milk decreased when acidic milk preparations were neutralized. In decaseinated bovine milk soluble zinc, iron, and copper were reduced 90%, 60%, and 50%, respectively, as the pH was raised from 4 to 7. Simultaneous precipitation of minerals and citrate was confirmed by analysis of washed precipitate. We propose that the diminished solubilities of zinc, iron, copper, magnesium, and citrate are linked to the precipitation of calcium phosphate through one or more mechanisms of coprecipitation. Such control on mineral solubility may have an impact upon mineral absorption from milk.


Gas gangrene pyaemia with myocardial abscess formation--fatal outcome from a rare infection nowadays.
We report a case of sudden death after gas gangrene. A 67-year-old male patient with diabetes mellitus and chronic renal failure (on haemodialysis three times a week) presented in the surgical emergency department with a severe swelling and crepitation in the right groin. No signs of trauma were present-except for a well-healed, 1-year-old scar after femoro-popliteal bypass surgery. Two days earlier, he had presented to the internal medicine department with epigastric pain and had left against medical advice. On readmission the patient was initially conscious and in a stable cardiopulmonary condition but developed sudden cardiocirculatory failure and underwent resuscitation. Despite all resuscitation measures, including the administration of high doses of catecholamines and the treatment of hyperkalemia, the patient died. Autopsy revealed septicaemia with rod-shaped gram-positive bacteria, typical of Clostridium perfringens, evidenced by multiple areas of myonecrosis. Abscess formation was found in the myocardium. Clostridial gas gangrene is a rare clinical condition. Unless immediate diagnosis and adequate therapy measures are taken, the outcome and chances for survival are poor as demonstrated by this case.


A Composite of Two Dimensional GeSe2 /Nitrogen-Doped Reduced Graphene Oxide for Enhanced Capacitive Lithium-Ion Storage.
A composite of two-dimensional (2D) GeSe2 nanosheets dispersed on N-doped reduced graphene oxide (GeSe2 /N-rGO) is fabricated via a simple hydrothermal method combined with post-selenization process. The high electronic conductivity and the substantial void spaces of the wrinkled N-rGO can improve the electrical conductivity of the active material and accommodate the volume evolution of GeSe2 nanosheets during the (de)lithiation processes, while GeSe2 nanosheets can reduce ion diffusion length effectively. Meanwhile, the unique layered structure is beneficial to the contact of the active material and electrolyte, and the reversibility of conversion reaction has also been improved. Furthermore, kinetics analysis reveals a pseudocapacitance-dominated Li+ -storage mechanism at high rates. In-situ X-ray diffraction analysis discloses that the conversion reaction has played a certain part in Li+ -storage. Thus, the GeSe2 /N-rGO composite delivers excellent rate capability and good long-term stability with a high reversible capacity of 711.0 mA h g-1 after 2000 cycles at 1 A g-1 .


Efficacy of mebendazole and albendazole for Ascaris lumbricoides and hookworm infections in an area with long time exposure for antihelminthes, Northwest Ethiopia.
The efficacy of mebendazole and albendazole in the treatment of Ascaris lumbricoides and hookworm infections was evaluated in school children in an area with long time exposure for broad spectrum anthelminthic drugs. Mebendazole exhibited cure rates of 90.6% and 83.5%; egg reduction rates of 96.7% and 94.2% against Ascaris lumbricoides and hookworm infections respectively. Albendazole showed a cure rate of 83.9% and egg reduction rate of 96.3% against Ascaris lumbricoides and a cure rate of 84.2% and egg reduction rate of 95% against hookworm infection. Albendazole appeared to be more effective against hookworm infection (egg reduction rate of 95% versus 94.2%, p = 0.04). Mebendazole and albendazole showed reduced efficacy against Ascaris lumbricoides and hookworm infections at the recommended doses. This may be a sign for emergence of drug resistance in this region. Care in routine use of the anthelminthes and continuous drug efficacy surveillance is recommended.


Sitting Height to Standing Height Ratio Reference Charts for Children in the United States.
To create reference charts for sitting height to standing height ratio (SitHt/Ht) for children in the US, and to describe the trajectory of SitHt/Ht during puberty. This was a cross-sectional study using data from the 1988-1994 National Health and Nutrition Examination Survey III, a strategic random sample of the US population. Comparison between non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican American groups was performed by ANOVA to determine if a single population reference chart could be used. ANOVA was used to compare SitHt/Ht in pre-, early, and late puberty. NHANES III recorded sitting height and standing height measurements in 9569 children aged 2-18 years of NHW (n = 2715), NHB (n = 3336), and Mexican American (n = 3518) ancestry. NHB children had lower SitHt/Ht than NHW and Mexican American children throughout childhood (P < .001). In both sexes, the SitHt/Ht decreased from prepuberty to early puberty and increased in late puberty. Sex-specific percentile charts of SitHt/Ht vs age were generated for NHB and for NHW and Mexican American youth combined. SitHt/Ht assessment can detect disproportionate short stature in children with skeletal dysplasia, but age-, sex-, and population-specific reference charts are required to interpret this measurement. NHB children in the US have significantly lower SitHt/Ht than other children, which adds complexity to interpretation. We recommend the use of standardized ancestry-specific reference charts in screening for skeletal dysplasias and have developed such charts in this study.


The neurological substrates for prosodic aspects of speech.
The ability to comprehend and produce the stress contrast between noun compounds and noun phrases (e.g., greenhouse vs. green house) was examined for 8 nonfluent aphasics, 7 fluent aphasics, 7 right hemisphere damaged (RHD) patients, and 22 normal controls. The aphasics performed worse than normal controls on the comprehension task, and the RHD group performed as well as normals. The ability to produce stress contrasts was tested with a sentence-reading task; acoustic measurements revealed that no nonfluent aphasic used pitch to distinguish noun compounds from phrases, but two used duration. All but one of the RHD patients and all but one of the normals produced pitch and/or duration cues. These results suggest that linguistic prosody is processed by the left hemisphere and that with brain damage the ability to produce pitch and duration cues may be dissociated at the lexical level.


[Laparoscopic choledochoscopy].
Of this study was to evaluate the treatment of common bile duct stones (CBDS) by laparoscopic choledochoscopy. Between 1997-2002, 9 patients (with age between 42-75 years) were treated laparoscopic for CBDS: 8 cases with choledocholithiasis; 1 case with pancreatic neoplasm. Laparoscopic choledochoscopy was performed in 7 cases (84.4%). We used the choledochoscope Pentax of 5 mm diameter and with work canal. We performed the CBD exploration with: transcystic approach-1 case; choledochotomy-6 cases. The CBD diameter was between 1.2-1.5 cm. The bile duct stones diameter were between 0.5-1.5 cm. We performed with successfully the laparoscopic choledochoscopy exploration and extraction of CBD stones to all patients. External biliary drainage (transcystic duct and with Kehr-tube) were done systematically. The major complication (choleperitoneum) occurred in 2 cases (28.5%). The occurrence of residual ductal stones was 0. The laparoscopic treatment of choledocholithiasis is feasible, safe and efficient.


Effect of some organic phosphorus and carbamate pesticides on Streptomyces scabies.
Of all the organic phosphorus and carbamate pesticides, tested on Streptomyces scabies, Thimet, Chlorothion, Dithane M-45, and Karathane, were effective at relatively low concentrations (1, 20, 16, and 115 ppm). Minimal inhibitory concentrations of these pesticides were the same in vitro as well as in vivo. The other organic phosphorus and carbamate compounds tested were less effective under the laboratory conditions of these tests.


[Response of facial soft tissues following interventions of mandibular regression. Frontal examination].
The variation of certain fundamental aesthetic parameters in patients (5) subjected to mandibular regression (Obwegeser-Dal Pont) is examined. The patients suffered from IIIrd class malocclusion. The examination was carried out on facial photographs (ratio 1:1) in front view.


Successful Treatment of Chronic Myeloid Leukemia With Dasatinib After Kidney Transplantation: A Case Report.
Chronic myeloid leukemia (CML) is a rare malignancy in kidney transplant (KT) recipients. Although dasatinib is the first-line treatment for CML, it has inhibitory activity against CYP3A4; this might increase the blood concentration of tacrolimus (administered to KT patients for immune suppression). Furthermore, tacrolimus can also increase blood concentrations of dasatinib through P-glycoprotein inhibition. Here, we report a case of sustained molecular remission of CML with prolonged first-line dasatinib therapy in a KT recipient being treated with tacrolimus. A 61-year-old woman developed CML-chronic phase (CML-CP) 38 months post KT. Her maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone. Considering the potential drug interaction with tacrolimus, dasatinib was administered at a low dose of 50 mg/day. Her immune status was evaluated regularly by assessing the mixed lymphocyte reaction (MLR) using an intracellular carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique; immunosuppressive therapy was adjusted accordingly. The patient achieved complete hematologic remission (CHR) after 1 month of dasatinib treatment. Six months after dasatinib treatment, she achieved a major molecular response. During the observation period, neither antibody-mediated nor acute cellular rejection were encountered in the patient. She remained in CHR with a major molecular response 12 months after the diagnosis of CML-CP. Data obtained from immune monitoring assays using CFSE-MLR helped us to successfully manage a KT recipient with CML-CP being treated with dasatinib. Drug-drug interactions are a key consideration while designing treatment regimens; such strategies would ensure that drug-drug interactions do not negatively affect the treatment outcomes.


Vaccination with recombinant tick antigens for the control of Ixodes scapularis adult infestations.
Antigens protective against Ixodes scapularis infestations were identified by cDNA expression library immunization (ELI) and analysis of expressed sequenced tags (EST). Three cDNAs protective against larval tick infestations, 4F8, with homology to a nucleotidase, and 4D8 and 4E6 of unknown function, were characterized and obtained as recombinant proteins for immunization studies. Vaccination trials with recombinant proteins demonstrated an effect of these antigens against I. scapularis larvae in a mouse model. Herein, we evaluated the effect of recombinant antigens on I. scapularis adult infestations on immunized sheep. Vaccination with recombinant 4D8, 4F8, 4E6 and the combination of all three antigens reduced adult tick infestations by 58, 12, 20, and 16%, respectively, when compared to the control group but was statistically significant for 4D8 and 4F8 only. Oviposition was reduced by 22-49% in all groups immunized with recombinant tick antigens (P<0.05). The overall efficacy of vaccine formulations considering the effect on tick infestations and oviposition averaged 33-71%. These antigens, and especially 4D8, appear to be good candidates for continued development of a vaccine for control of tick infestations.


Treatment of actinic keratoses and photodamage with non-contact fractional 1540-nm laser quasi-ablation: an ex vivo and clinical evaluation.
The main use of non-ablative fractional photothermolysis today is for the improvement of wrinkles and scars. The purpose of this work was to evaluate the effect of a "classic" non-ablative fractional 1540 nm on facial photodamaged skin and actinic keratoses. Seventeen patients with facial actinic keratoses (AKs) and photodamage underwent two or three laser treatments with fractional 1540-nm erbium glass laser at fluences of 75 mJ, 15 ms pulse duration, and 10-mm spot size in non-contact mode. Two blinded assessors and participants evaluated clinical improvement of treatment areas after 3 months, using a quartile grading scale (no improvement = 0, 1-25% improvement = 1, 26-50% = 2, 51-75% = 3, and 76-100% = 4). Three months after the last treatment, the mean level of improvement was 3.4 ± 0.72 for AK and 3.3 ± 0.54 for skin appearance. Adverse events observed after each treatment were moderate erythema, mild edema, erosions (two cases), and mild desquamation. No scarring or post-inflammatory pigmentary changes were observed. The clinical results were supported by histological changes observed in Yucatan pig studies in vivo and ex vivo. The 1540-nm fractional erbium glass laser in the non-contact mode is a safe and effective treatment for facial photodamage and AKs.


The use of contrast enhanced thoraco-abdominal CT in patients with non-traumatic undifferentiated hemodynamic shock.
To assess the role of thoraco-abdominal computed tomography (CT) in patients with undifferentiated shock in the emergency department (ED). Secondary aim was to assess common etiologies for undifferentiated shock. This was a single-center, retrospective study evaluating patients with undifferentiated shock who underwent a dedicated "shock protocol" CT in the ED. CT included a non-contrast thoraco-abdominal scan followed by arterial thoraco-abdominal and abdominal portal phases. Patients' clinical records, laboratory, imaging data and all-cause 90-days mortality were collected. Patients' shock category (i.e., distributive, cardiogenic, hypovolemic, obstructive, multifactorial, and unknown) and etiology for shock were retrospectively determined based on patients' medical records. Effect of CT on patients' diagnosis and management was assessed based on physicians' reports before and after CT. Overall, 102 patients were scanned between December 2018 and December 2020. Distributive shock was the most prevalent type with 47.1% of all patients (48/102), followed by hypovolemic shock (17/102, 16.7%). Based on clinical data and CT reports, shock etiology was diagnosed for 89.2% (91/102) patients. Sepsis was the most common etiology in 50% of patients, followed by non-traumatic hemorrhage (15/102, 14.7%). Overall, 90-day mortality was 58.8%. Shock protocol CT led to change in differential diagnosis in 49% of patients and to change in management in 42.2%. Contrast-enhanced shock protocol CT can help in shock differentiation, assessment of etiology and in management of patients presenting to the ED with undifferentiated shock.


Preference-based measure of health-related quality of life and its determinants in sickle cell disease in Nigeria.
Health-related quality of life (HRQL) and economic burden are important issues for people with sickle cell disease (SCD) owing to better survival due to medical advances. Preference-based or utility information is necessary to make informed economic decisions on treatment and alternative therapies. This study aimed to assess preference-based measures of HRQL in sickle cell patients. Data were collected from two SCD outpatient clinics in Ibadan, Nigeria. A standard algorithm was used to derive utility scores, and measure SF-6D from the SF-36. A multivariate regression model was used to assess predictors and their impact. A combination of socio-demographic, bio-physiological and psychosocial variables predicted utility score in people with SCD. Socio-demographic and bio-physiological factors explained 7.5% and 17.9% of the variance respectively, while psychosocial factors explained 4.9%. Women had lower utility scores with a small effect size (d = 0.17). Utility score increased with level of education but decreased with age, anxiety, frequency of pain episodes and number of co-morbidities. Utility score in SCD was low indicating a substantial impact of the disease on HRQL of patients and the value they place on their health state due to the limitations they experienced. Interventions should include both clinical and psychosocial approach to help in improving their quality of life of the patients.


Translation, validation and psychometric properties of the Albanian version of the Nurses Professional Competence Scale Short form.
The primary aim of this study was the translation and psychometric validation of the Albanian Nurse Professional Competence Scale Short Form (A-NPCS-SF) for further application in Albanian healthcare settings. The multiphase design used to develop the A-NPCS-SF comprised (1) cultural and linguistic validation, (2) content and face validity, and (3) construct validity. The A-NPCS-SF showed adequate content validity. Confirmatory factor analysis supported the six-factor structure of the A-NPCS-SF to explain the data obtained from the nurses. The A-NPCS-SF showed evidence of validity and reliability in measuring four professional competencies. Having an appropriate scale in Albanian for professional competence self-assessment by nurses constitutes an essential step in measuring these competencies. (www.actabiomedica.it).


Visual motion and cortical velocity.
Recent studies have revealed some remarkably simple relationships between visual performance and the neuroanatomy of the visual pathways. The visual field is mapped topographically on the surface of the striate cortex in man; the projection is large for the central visual field and is progressively compressed towards the periphery. Visual acuity decreases with distance from the fovea in proportion to the estimated cortical magnification factor, M (the extent of striate cortex in millimetres corresponding to a degree of arc in visual space). If a stimulus is magnified at peripheral locations in proportion to 1/M, it becomes equally resolvable across the visual field. This scaling procedure (M-scaling) maintains equivalence of the cortical projection of stimuli with different visual field loci. We have used M-scaling to investigate motion perception as a visual field variable. We report here that both the lower threshold of motion and adaptation to motion are uniform for M-scaled stimuli, and are related to the velocity of the 'cortical image'.


Is hepatic ultrasonography a valid alternative tool to liver biopsy? Report on 507 cases studied with both techniques.
In order to evaluate the diagnostic potential of liver ultrasonography (US), the charts of 23 cases with normal liver, 424 patients with chronic widespread, and 60 patients with focal hepatic diseases, who had undergone both US and liver biopsy, were reviewed. The positive predictive value of US was good in all hepatic disorders (range 86.9-96.5%), while its negative predictive value was very low (range 14.1-42.5%) in the various forms of widespread liver disease and suitable for screening purposes (74%) in focal lesions. Of the 507 cases, 39 with an ultrasonically suspected liver mass also underwent an echo-guided fine-needle aspiration, which showed a high sensitivity (85%) in the 27 biopsy-proved malignant lesions and excluded tumor cells in the remaining 12 cirrhotic cases. As regards US tissue diagnosis, hepatic tumors, fatty infiltration, and fibrosis were detected in 88%, 60%, and 49% of cases, respectively. Fat and fibrous content on biopsy were similarly and significantly correlated with both echo pattern and sound attenuation. Overall results suggest that in the group of widespread hepatic disorders the usefulness of US is greatly reduced by the fact that the patient's actual condition is not likely to be negative if US examination is normal and by the impossibility of differentiating fat from fibrosis. In focal lesions, the diagnostic value of US appears high and the method may frequently provide conclusive proof of the tumor if a positive cytodiagnosis on echo-guided aspirated material is done.


MRI and Active Surveillance for Prostate Cancer.
Since the introduction of Prostate-Specific Antigen (PSA) screening, prostate cancer mortality has decreased [...].


Risk factors for idiopathic cerebellar ataxia of late onset.
In an attempt to identify risk factors for the development of idiopathic cerebellar ataxia (IDCA) we performed a case-control study of 59 IDCA patients. Hypertension and medicine intake were less frequent in IDCA than in neurological controls. Multiple logistic regression yielded an odds ratio (OR) for hypertension of 0.13 (95% confidence interval: 0.00-1.02, P=0.0527) and medicine intake of 0.10 (95% confidence interval: 0.00-0.72, P=0.0157). In contrast, we did not identify an association of IDCA with a number of medical diseases, head trauma, smoking, alcohol intake, rural living and well-water drinking. Some of these factors have been previously shown to be associated with other neurodegenerative diseases. In addition, serum antibody titers against neurotropic viruses were not elevated in IDCA.


Global analysis of chromosome 1 genes among patients with lung adenocarcinoma, squamous carcinoma, large-cell carcinoma, small-cell carcinoma, or non-cancer.
The present study aimed at investigating genetic variations, specific signal pathways, or biological processes of chromosome 1 genes between subtypes and stages of lung cancer and prediction of selected targeting genes for patient survival rate. About 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without caner were integrated from 16 databases and analyzed in the present study. Three (ASPM, CDC20, KIAA1799) or 28 genes significantly up- or down-expressed in four subtypes of lung cancer. The activated cell division and down-regulated immune responses were identified in patients with lung cancer. Keratinocyte development associated genes S100 and SPRR families dominantly up-expressed in SCC and AKT3 and NRAS in SCLC. Subtype-specific genes of ADC, SCC, LCC, or SCLC were also identified. C1orf106, CAPN8, CDC20, COL11A1, CRABP2, and NBPF9 up-expressed at four stages of ADC. Fifty six related with keratinocytes or potassium channels up-expressed in three stages of SCC. CDC20, IL10, ECM1, GABPB2, CRABP2, and COL11A1 significantly predicted the poor overall survival of ADC patients and S100A2 and TIMM17A in SCC patients. Our data indicate that a number of altered chromosome 1 genes have the subtype and stage specificities of lung cancer and can be considered as diagnostic and prognosis biomarkers.


Effects of temperature inactivation of penicillin-binding protein 2 on envelope growth in Escherichia coli.
The transition from rod-shaped to spheroidal cells was studied in a temperature-sensitive strain (SP45) of Escherichia coli K12, carrying a mutation (pbpA) in the gene coding for penicillin-binding protein 2 (PBP-2). This transition imposed by the restrictive temperature was associated with reduction of peptidoglycan/surface area and of cellular osmotic stability. Addition of nalidixic acid (20 micrograms/ml) at the temperature shift from 30 to 42 degrees C resulted in lysis of some cells and appearance of spheroidal bulges along the cylinders in other cells, consistent with the hypothesis of envelope weakening due to inactivation of PBP-2.


Spontaneous subdural haemorrhage from an arachnoid cyst: a case report and literature review.
We discuss a spontaneous subdural haematoma (SDH) arising from an arachnoid cyst in a healthy adult male, presenting with headache and vomiting. Imaging revealed a large SDH communicating with an arachnoid cyst and intracystic haemorrhage. The patient fully recovered with surgical evacuation. We also discuss the causes of spontaneous SDH, and specific risk factors for bleeding in arachnoid cysts, as well as review the literature on spontaneous SDH from arachnoid cysts - a rare but serious complication.


Latest progress on the molecular mechanisms of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a serious life-threatening lung disease, and the median survival period of PF patients after diagnosis is only 2.5-3.5 years. At present, there are no effective drugs or therapeutics to reverse or even inhibit IPF. The main pathological characteristics of pulmonary fibrosis (PF) include damage to alveolar epithelial cells, fibroblast activation and extracellular matrix accumulation, which gradually lead to damage to the lung structure and decreased lung function. It is important to understand the cellular and molecular mechanisms of PF comprehensively and clearly. In this paper, critical signaling pathways related to PF were reviewed to present updates on the molecular mechanisms of PF.


Monitoring the N-glycosylation of plant glycoproteins by fluorophore-assisted carbohydrate electrophoresis.
We have evaluated the efficiency of a fast, simple and efficient method, fluorophore-assisted carbohydrate electrophoresis (FACE), for the characterization of plant N-linked glycans. After their enzymatic release from plant glycoproteins, N-glycans were reductively aminated to the charged fluorophore 8-aminonaphthalene-1, 3, 6-trisulfonic acid (ANTS) and separated using high resolution polyacrylamide gel electrophoresis. In addition, an affinity purification procedure using concanavalin A was developed for separation of ANTS-labeled high-mannose-type N-glycans from other plant oligosaccharides.


The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis.
A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma.


Three-dimensional super-resolution protein localization correlated with vitrified cellular context.
We demonstrate the use of cryogenic super-resolution correlative light and electron microscopy (csCLEM) to precisely determine the spatial relationship between proteins and their native cellular structures. Several fluorescent proteins (FPs) were found to be photoswitchable and emitted far more photons under our cryogenic imaging condition, resulting in higher localization precision which is comparable to ambient super-resolution imaging. Vitrified specimens were prepared by high pressure freezing and cryo-sectioning to maintain a near-native state with better fluorescence preservation. A 2-3-fold improvement of resolution over the recent reports was achieved due to the photon budget performance of screening out Dronpa and optimized imaging conditions, even with thin sections which is at a disadvantage when calculate the structure resolution from label density. We extended csCLEM to mammalian cells by introducing cryo-sectioning and observed good correlation of a mitochondrial protein with the mitochondrial outer membrane at nanometer resolution in three dimensions.


Determinants of HIV prevalence amongst female IDU in Madrid.
To explore the multitude possible factors associated with HIV in a population of female injecting drug users (IDUs) in Madrid, Spain. A cross-sectional study was undertaken and because of the lack of sampling frame in this population, a convenience sample was recruited from drug treatment, methadone services and street settings. Face to face interviews were conducted with 304 female IDUs during October 1995-March 1996. HIV status was determined from antibody testing of blood samples or from written confirmation of HIV test results from a physician. A hierarchical logistic regression model was used to identify direct and indirect relationships with HIV prevalence. HIV prevalence in the sample of female IDUs for which HIV status was known (n = 262) was 63%. Factors independently associated with HIV prevalence in the regression analysis included: having a regular HIV positive sexual partner [odds ratio (OR): 12.2], age over 34 years (OR: 3.4), no fixed address (OR: 2.9), co-infection with a sexually transmitted infection (STI) in the last year (OR: 2.8) and ever shared needles (OR: 2.6). The documentation of the context of risk behaviour in female IDU is important to predict the course of the epidemic and to develop prevention strategies. The sexual partners of female IDUs in Spain are important components in explaining the HIV epidemic in this population as other risk factors, including high risk drug taking behaviour. The findings also highlight the need to target homeless IDUs women and inmate women with outreach services offering preventive interventions. More effective STI prevention and control strategies are also warranted.