Synthesis and evaluation of the anxiolytic activity of some phthalimide derivatives in mice model of anxiety.
The aim of the present study was to synthesis a series of phthalimides based on our previous works and examine their anxiolytic properties. Using a three steps process, phthalimides were prepared from the corresponding di-methyl phthalate derivatives. Phthalic anhydride was nitrated to produce 3-nitrophthalic acid. Ring closer of either 3-nitrophthalic acid or di-methyl phthalate with urea were carried out in reflux condition. Final compounds were prepared by base catalyzed condensation of 4-methylbenzoyl chloride, benzoyl chloride and benzyl chloride with the resulting imides. From the tested compounds, only N-benzoyl 3-nitro-phthalimide was shown to produce anxiolytic activity by increasing the number of entries and time spent in open arms at 10 mg/kg.


Elderly migration: household versus individual approaches.
"This paper employs a household approach to elderly migration analyses and compares it with the traditional individual approach. The first part of the paper develops some concepts about household mobility and relates them to individual mobility. It then compares the two mobility measurements in a case study using the Public Use Microdata Sample (PUMS) from the 1990 [U.S.] Census. The results show that the mean household size for the elderly moving together tends to be smaller than that for elderly stayers. It also demonstrates the utility of the household approach on profiling elderly movers' living arrangement choices. The second part of the paper calibrates a set of discrete choice models based on the household and individual approaches."


Top-Down Glycopeptidomics Reveals Intact Glycomacropeptide Is Digested to a Wide Array of Peptides in Human Jejunum.
Bovine milk κ-casein-derived caseinomacropeptide (CMP) is produced in large quantities during cheese-making and has various biological activities demonstrated via in vitro and in vivo experiments. Previous studies examined protein degradation and peptide release after casein or whey protein consumption. However, whether purified intact CMP that is partially glycosylated survives intact to its presumed site of bioactivity within the gut remains unknown. The aim of this study was to determine the extent to which purified intact CMP (including glycosylated forms) is digested into peptide fragments within the jejunum of healthy human adults after consumption. Jejunal fluids were collected from 3 adult participants (2 men and 1 woman, age: 27 ± 7 y; BMI: 23 ± 1 kg/m2) for 3 h after consuming 37.5 g of purified intact CMP. CMP and CMP-derived peptides were isolated from the collected jejunal fluids by ethanol precipitation and solid-phase extraction and identified by MS-based top-down glycopeptidomics. Relative abundances of CMP and CMP-derived peptides were compared qualitatively between the feed and the jejunal fluids. Intact CMP was dominant in feeding material, accounting for 90% of the total ion abundance of detected peptides, and in very low abundance (<2%) in the jejunal fluids. CMP-derived fragment peptides ranging from 11 to 20 amino acids in length were predominant (accounting for 68-88% of the total peptide ion abundance) in jejunal fluids during 1-3 h post consumption. This study demonstrates that intact CMP (including glycosylated forms) is mostly digested in the human jejunum, releasing a wide array of CMP-derived peptide fragments. Some of the CMP-derived peptides with high homology to known bioactive peptides consistently survived across 3 h of digestion. Therefore, future research should examine the biological effects of the partially digested form-the CMP-derived fragments-rather than those of intact CMP.


Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine.
To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine. Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded. 169 (4,45%) patients had Covid-19 infection, of which 12 (7.1 %) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P < .05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P < .05). There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19.


Determination of evoked potentials in occupational and environmental medicine: a review.
The measurement of cerebral evoked and event-related potentials is a promising technique for assessment of subclinical neurotoxicity and has recently been introduced into occupational and environmental medicine. Evoked potentials consist of somatosensory, visual, and auditory evoked potentials, and event-related potentials include the P300 potential. Measurement of these potentials can localize central nervous system impairments caused by exposure to a wide variety of hazardous factors in the workplace and the general environment. This paper is intended to provide an overview of research utilizing these potentials to evaluate the effects of work-related factors. The available data indicate that these potentials are sensitive and reliable methods that are easily standardized and practical to apply in the field setting. Researchers should note, however, that several covariates such as age, skin or body temperature, height, alcohol ingestion, and intelligence can influence assessment of these cerebral potentials in clinical and epidemiologic studies.


Proteoglycans in the compressed region of human tibialis posterior tendon and in ligaments.
Proteoglycan content and tissue morphology were examined in tendons and ligaments from 24 cadavers, ranging in age at the time of death from 1.5 months to 83 years. The region of the human tibialis posterior tendon that passes under the medial malleolus was characterized by cells having a rounded shape, positive staining with alcian blue, and higher glycosaminoglycanuronic acid content than in the more proximal region of the same tendon. Analysis of proteoglycans by sodium dodecyl sulfate/polyacrylamide gel electrophoresis indicated that the predominant small proteoglycan of the proximal/tensional region was decorin, whereas two types of small proteoglycans (decorin and biglycan) and large proteoglycans were present in the region passing under the medial malleolus and presumably subjected to compressive and shear forces in addition to tension. The pattern of proteoglycan accumulation in the compressed region of tendon was basically similar for all individuals and showed no distinctive trends related to age after puberty. In terms of type and amount of proteoglycan, the patellar tendon was like the tensional region of the tibialis posterior. Glycosaminoglycan content in the lateral collateral ligament and anterior cruciate ligament, however, was twofold higher than in the tendons. The ligaments contained large as well as small proteoglycans, just as in the compressed region of tendon.


Incorporation in lipid microparticles of the UVA filter, butyl methoxydibenzoylmethane combined with the UVB filter, octocrylene: effect on photostability.
The aim of this study was to reduce the photoinstability of butyl methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by incorporating it in lipid microparticles (LMs) alone or together with the UVB filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion technique, using glyceryl behenate as lipid material and poloxamer 188 as surfactant. The LMs were characterized by release studies, scanning electron microscopy, and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2% and 10.6%, respectively. In order to reproduce the conditions prevalent in commercial sunscreen products, the photoprotective efficacy of the LMs was evaluated after their introduction in a model cream (oil-in-water emulsion) containing a mixture of UVA and UVB filters. A small but statistically significant decrease in BMDBM photodegradation was obtained when the UVA filter was encapsulated alone into the LMs (the extent of degradation was 28.6% +/-2.4 for non-encapsulated BMDBM and 26.0% +/-2.5 for BMDBM-loaded microparticles). On the other hand, the co-loading of OCR in the LMs produced a more marked reduction in the light-induced decomposition of microencapsulated BMDBM (the UVA filter loss was 21.5% +/-2.2). Therefore, incorporation in lipid microparticles of BMDBM together with the sunscreen OCR is more effective in enhancing the UVA filter photostability than LMs loaded with BMDBM alone.


Prevalence of tuberculosis among health care workers in tuberculosis specialized hospitals in China.
Tuberculosis (TB) specialized hospitals are playing an increasingly important role in the diagnosis and treatment of patients with TB in China. This study aimed to investigate the prevalence of TB among health care workers (HCWs) in TB specialized hospitals in China. We conducted a cross-sectional survey to collect longitudinal information on the number of HCWs and patients with TB from HCWs among 203 TB hospitals in China. Overall, these 186 TB cases accounted for the incidence of 985 per 100,000 population. The prevalence ratios among medical professionals (PR = 2.40) and laboratory technicians (PR = 2.17) were significantly higher than other hospital staff (PR = 1.04). In addition, general hospitals with TB clinics had the highest prevalence ratio of TB (PR = 5.15), while designated TB hospitals had the lowest prevalence ratio (PR = 1.48). Our findings demonstrated that HCWs are suffering from an increased risk of infection with TB in China, and medical professionals (physicians and nurses) and general hospitals with TB clinics have the highest prevalence ratio of TB.


Use of restriction endonucleases and exonuclease III to expose halogenated pyrimidines for immunochemical staining.
We describe an enzymatic procedure for exposure of single-stranded DNA (ssDNA) containing the halogenated pyrimidines (HdUrd) bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) in single cells to antibodies that bind to HrdUrd only in ssDNA. Production of ssDNA was accomplished by digesting the DNA using either restriction endonucleases alone or endonucleases followed by exonuclease III. The enzymatic production of ssDNA was maximal when 0.1 N HCl or 0.1 M citric acid plus Triton X-100 was added to extract nuclear proteins prior to enzymatic denaturation. The restriction endonucleases Bam HI, Dde I, Eco RI, and Hind III produced significant ssDNA when used alone to allow binding of detectable amounts of the anti-HdUrd antibody IU-4 in Chinese hamster ovary cells labeled with 10 microM BrdUrd or 10 microM IdUrd. However, these treatments did not expose sufficient ssDNA to allow binding of IU-1, an anti-HdUrd antibody with lower binding affinity. IU-4 binding was most intense after treatment with Eco RI. Treatment with exonuclease III following endonuclease digestion allowed substantially more IU-4 binding.


Development of anti-atherosclerosis therapy based on the inflammatory and proliferative aspects of the disease.
Atherosclerotic cardiovascular diseases are a worldwide major public health concern. Atherosclerosis is driven by a chronic inflammatory process which is present since the early stages of the disease, as a response to endothelium aggression by a variety of offending agents, to subsequent formation of foam cells, atheromatous plaque development and the clinical complications of the disease, due to plaque rupture and thromboembolic acute episodes. However, drug therapies directed to inflammation are lacking in the clinical practice, despite an increasing effort of research and identification of several potential molecular targets. Effective medical treatments available for primary and secondary prevention are restricted to cholesterol lowering statins and anti-platelet drugs such as aspirin. Here, steps of atherogenesis, cells involved in the process, secreted pro- and anti-inflammatory factors, the concept of unstable and stable atheroma plaques, the intertwining among inflammation, lipid arterial deposit, thrombus formation, therapeutically targetable mechanisms, monoclonal antibodies, enzymatic inhibitors, phytotherapeutic compounds and anti-proliferative agents used in cancer chemotherapy, drugs tested in experimental animals and at the clinical stage are shortly reviewed. Because statins and anti-platelet drugs use do not prevent more than 30-40% of the major cardiovascular events, the development of novel therapeutic tools is desirable. Nonetheless, atherosclerosis is a chronic process presumably demanding long-standing treatments, so that the safety, opportunity, cost-effectiveness and development of drug resistance are major issues that challenge the introduction of novel, inflammation-oriented therapies.


An ECG recording front-end with continuous-time level-crossing sampling.
An ECG recording front-end with a continuous- time asynchronous level-crossing analog-to-digital converter (LC-ADC) is proposed. The system is a voltage and current mixed-mode system, which comprises a low noise amplifier (LNA), a programmable voltage-to-current converter (PVCC) as a programmable gain amplifier (PGA) and an LC-ADC with calibration DACs and an RC oscillator. The LNA shows an input referred noise of 3.77 μVrms over 0.06 Hz-950 Hz bandwidth. The total harmonic distortion (THD) of the LNA is 0.15% for a 10 mVPP input. The ECG front-end consumes 8.49 μW from a 1 V supply and achieves an ENOB up to 8 bits. The core area of the proposed front-end is 690 ×710 μm2, fabricated in a 0.18 μm CMOS technology.


Evaluation of the Stability of Polymeric Materials Exposed to Palm Biodiesel and Biodiesel⁻Organic Acid Blends.
The aim of the present work is to evaluate the impact of pure palm biodiesel fuel (B100) and biodiesel blends with 0.32% oleic, palmitic, acetic, myristic, and stearic acids on the properties of some polymeric materials used commonly in the manufacture of auto parts such as the polyamide 66 (PA66), polyoxymethylene (POM), and high-density polyethylene (HDPE). The effects of the B100 and B100⁻acid blends on polymeric materials were examined by comparing changes in the gain/loss of mass and by measuring the hardness, the impact strength, and the tensile strength of the materials at the end of the exposure. The characterization of the polymers was carried out before and after exposure by using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). After the immersion in B100⁻acids blends, the HDPE exhibited an increase in mass of 5%, which was very similar in all blends. The PA66 showed a small decrease in weight (2% approx.) in all mixtures. The POM presented an increase in the percentage of weight in the mixture of B100 with acetic acid of 0.3%. A decrease was observed in the crystallinity of the HDPE when exposed to blends of B100⁻acids. This behavior may be associated with a plasticizing effect in the HDPE exposed to the blends. The mechanical properties of POM and HDPE showed no significant changes after immersion in the fuels. On the other hand, PA66 exhibited a significant decrease in maximum stress value after immersion in B100, B100⁻oleic acid and B100⁻palmitic acid blends. The variation of the mechanical properties of the PA66 after exposure to B100 was potentiated by addition of organic acids. The assessed polymers did not undergo appreciable changes in the chemical structure of the samples after immersion in the fuels, so the variation in the mechanical properties could be explained by physical absorption of the fuel into the polymers.


[Learning together to work together: interprofessional education, a myth or reality?].
This article offers a review of the literature on interprofessional education (EIP), a form of education which brings together members of two or more professions in a joint training. In this course, participants gain knowledge through other professionals and about them. The goal of EIP is to improve collaboration between health professionals and the quality of patient care. The EIP is booming worldwide and seems for from a mere fad. This expansion can be explained by several factors: the increasing importance attributed to the quality of care and patient safety, care changes (aging population and increasing chronic diseases) and the shortage of health professionals. The expectations of the EIP are large, while the evidence supporting its effectiveness is being built.


[Effect of primary aliphatic amines on oxidative phosphorylation in rat liver mitochondria].
The dynamics of primary aliphatic amines (ethylamine, propylamine) effects on the processes of oxidative phosphorylation in rat liver mitochondria was estimated. The inhibiting action of ethylamine and propylamine on the oxidative phosphorylation processes in the rat liver mitochondria was revealed.


[Epidemiologic study of cytomegalovirus infection in patients with diabetes mellitus].
To understand the relations between human CMV infection and diabetes mellitus, 955 blood samples were tested for cytomegalovirus (CMV) antibodies from 845 diabetes mellitus and 110 healthy persons. Positive rates of CMV IgM, CMV IgA, CMV IgG antibodies were significantly higher in diabetes mellitus patients than in controls. 845 diabetes mellitus patients were devided into 4 and 5 groups according to the courses of disease and age of disease onsets respectively. Positive rates of CMV IgM antibody was significantly higher in younger patients and/or patients recently suffering from diabetes mellitus. Results showed that CMV infection was important in the pathogenesis of diabetes mellitus and primary CMV infection rates was significantly higher in younger patients and/or patients suffering from diabetes mellitus.


Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes.
Metformin is the endorsed first-line glucose-lowering drug for treating patients with type 2 diabetes but despite more than 50 years of use, no consensus has been reached on its mechanisms of action. In this study, we investigated the glucose-lowering effects of metformin in individuals with type 2 diabetes and non-diabetic individuals. We performed a randomised, placebo-controlled trial in 24 individuals with recent-onset type 2 diabetes (diabetes duration 50 [48] months) who had good glycaemic control (HbA1c 48 mmol/mmol [6.5%]). The studies were conducted at Aarhus University Hospital between 2013 and 2016. Participants were randomised to receive either metformin (2000 mg/day, n = 12, MET group) or placebo (n = 12, PLA group) for 90 days, using block randomisation set up by an unblinded pharmacist. Two participants withdrew from the study prior to completion and were replaced with two new participants receiving the same treatment. In addition, we recruited a group of non-diabetic individuals with similar age and BMI (n = 12, CONT group), who were all treated with 2000 mg metformin daily. Before and after treatment all individuals underwent studies of whole-body glucose metabolism by non-steady-state [3-3H]glucose kinetics, hyperinsulinaemic-euglycaemic clamping, indirect calorimetry, metabolomics, dual x-ray absorptiometry and muscle biopsies. The primary study endpoint was the effect of metformin treatment on lipid kinetics as well as glucose rate of disappearance (Rd) and endogenous glucose production (EGP). One participant from the CONT group withdrew due to intolerable gastrointestinal side-effects and was excluded from analysis. As expected, metformin treatment lowered fasting plasma glucose (FPG) in the MET group (~1.5 mmol/l, p < 0.01), whereas no effect was observed in the PLA and CONT groups. Body weight and composition did not change in any of the groups. In both of the metformin-treated groups (MET and CONT), basal glucose Rd, EGP and glucagon levels increased by ~30% (p < 0.05) whereas this was not the case in the PLA group. Ninety days of metformin treatment resulted in similar increases in EGP and glucose Rd in individuals with recent-onset type 2 diabetes and in non-diabetic control individuals. These results challenge the existing paradigm that metformin primarily acts in the liver by inhibiting EGP, at least in individuals with type 2 diabetes of short duration and who have discretely affected glycaemic status. Whether metformin increases basal glucose Rd by facilitating glucose uptake in other tissues such as the intestines remains to be further clarified. ClinicalTrials.gov NCT01729156 FUNDING: This study was supported by grants from The Danish Council for Independent Research | Medical Sciences, Aase Danielsen Fund, the Novo Nordisk Foundation, the Danish Diabetes Association and the Danish Diabetes Academy supported by the Novo Nordisk Foundation.


Raman spectroscopy and imaging of beta-carotene in live corpus luteum cells.
Raman spectroscopy has been used to identify and locate beta-carotene within individual living luteal cells. The cells were either freshly prepared or cultured; the latter was incubated in the presence or absence of beta-carotene in the form of enriched bovine high-density lipoprotein. Luteal cells were investigated using several Raman spectroscopic and imaging techniques. These techniques did not give accurate concentration levels of beta-carotene within parts of the cell but illustrated the distribution of the molecule. Freshly prepared luteal cells were found to contain an appreciable concentration of beta-carotene. Over a period of several days, the concentration gradually reduced to a nearly undetectable level; similar results were found for cells cultured in the absence of the beta-carotene. For cells cultured in the presence of beta-carotene, the molecular concentration was maintained for as long as 2 weeks. The Raman spectra of fragmented cells showed that the beta-carotene is predominantly localised in the lipid-rich cell components, with the concentration highest in the microsomal fraction. The Raman imaging techniques revealed that beta-carotene was spread over the entire volume of the luteal cells with higher levels occurring at distinct sites, including the surface.


Health-related quality of life, satisfaction, and economic outcome measures in studies of prostate cancer screening and treatment, 1990-2000.
Prostate cancer outcomes research incorporates a broad spectrum of endpoints, from clinical or intermediate endpoints, such as tumor shrinkage or patient compliance, to final endpoints, such as survival or disease-free survival. Three types of nontraditional endpoints that are of growing interest-health-related quality of life (QOL), satisfaction with care, and economic cost impact-hold the promise of improving our ability to understand the full burden of prostate cancer screening and treatment. In this article we review the last decade's published literature regarding the health-related QOL, satisfaction, and economic outcomes of prostate cancer screening and treatment to determine the "state of the science" of outcomes measurement. The focus is the enumeration of the types of outcome measurement used in the studies not the determination of the results of the studies. Studies were identified by searching Medline (1990-2000). Articles were included if they presented original data on any patient-centered outcome (including costs or survival alone) for men screened and treated for prostate cancer. Review papers were excluded unless they were quantitative syntheses of the results of other primary studies. Economic and decision analytic papers were included if they presented information on outcomes of real or hypothetical patient cohorts. Each retrieved article was reviewed by one of the authors. Included papers were assigned one primary, mutually exclusive study design. For the "primary data" studies, information was abstracted on care setting, dates of the study, sample size, racial distribution, age, tumor differentiation, tumor stage, survival, statistical power, and types of outcomes measures (QOL-generic, QOL-cancer specific, QOL-prostate cancer specific, satisfaction, costs, utilities, and other). For the "economic and decision analytic" papers, information was abstracted on stage of disease, age range, outcomes, costs, and whether utilities were measured. Of the 198 included papers, there were 161 primary data papers categorized as follows: randomized trial (n = 28), nonrandomized trial (n = 13), prospective or retrospective cohort study (n = 55), case-control study (n = 0), cross-sectional study (n = 63), and meta-analysis (n = 2). The remaining 37 papers were economic and decision analytic papers. Among the 149 primary data papers that contained patient outcome data, there were 42 standard instruments used, accounting for 44% (179 of 410) of the measures overall. Almost three-quarters (71%) of papers included one, two, or three outcomes measures of all types (standard and nonstandard); three papers included seven outcomes measures, and one paper included nine. Over the 11-year time period, there was a nonstatistically significant trend toward more frequent use of standardized QOL instruments and a statistically significant trend toward increased reporting of race (P = .003). Standardization of measurement of health-related QOL, satisfaction with care, and economic cost effect among men screened and treated for prostate cancer is needed. A core set of similar questions, both generic and disease-specific, should ideally be asked in every study, although investigators should be encouraged to include additional question sets as appropriate to individual studies to get a more complete picture of how patients screened and treated for this condition are doing over time.


Pleomorphic lipoma of the oral cavity. Report of a case.
Pleomorphic lipoma (PL) is a rare benign tumor mainly located in the upper back, upper shoulders, and back of the neck in elderly men. More rarely it is located in the head and neck region and in the oral cavity. The differential diagnosis should be made with sclerosing liposarcoma and well-differentiated liposarcoma. A 59-year-old male patient was referred for the presence of a lesion involving the marginal and adherent gingiva of teeth # 5; this lesion extended into the vestibular mucosa. The lesion had a 2 cm diameter, showed no tenderness, had a hard-parenchymatous consistency, was mobile on the underlying tissues and was covered by normal appearing mucosa. Under local anesthesia, the lesion was completely removed. A free gingival graft from the palate was used to cover the defect. Microscopically, it was possible to observe mature adipocytes, spindle cells and rare ''floret-like'' cells. Lipoblasts and mitoses were absent. The definitive pathologic diagnosis was pleomorphic lipoma. No recurrences were present after a 5 years follow-up. Local excision is adequate for PL and the tumor does not recur.


Lifetime of peroxyl radicals of poly(U), poly(A) and single-and double-stranded DNA and the rate of their reaction with thiols.
Peroxyl radicals of poly(U), poly(A), and single- and double-stranded DNA have been produced by photolysing H2O2 in oxygenated aqueous solution in presence of the substrates. The peroxyl radicals are formed by the reaction of OH radicals with the polynucleotides followed by addition of oxygen. The lifetime of the peroxyl radicals and the rate constant of their reactions with the thiols cysteamine, glutathione and dithiothreithol have been measured by time-resolved e.s.r. spectroscopy. The unusually long lifetimes range from 0.2 to 3.3 s. The activation energy for the decay for all four substrates is 10.3 +/- 1 kcal/mol (43 kJ mol-1). The reaction rate constants with the thiols range from k = 0.8 X 10(4) to 1.3 X 10(5) dm3 mol-1 s-1. The reactions of the thiols with the peroxyl radical of poly(U) are known to prevent strand break formation. This shows that the peroxyl radicals of poly(U) observed by e.s.r. are intermediates in the pathway leading to strand break formation.


Effect of Preoperative Medical Status on Microsurgical Free Flap Reconstructions: A Matched Cohort Analysis of 969 Cases.
Free tissue transfers have become standard for a wide variety of reconstructive purposes. In an era of increasing economic pressure, it is important to precisely define appropriate candidates and indications for a complex surgery to optimize efficiency and patient outcomes. This study evaluates the feasibility to perform microsurgical procedures in a medically compromised patient cohort at a major academic microsurgical center. Within 7 years, 897 patients underwent 969 microvascular free flap reconstructions. The data were retrospectively screened for patients' demographics, perioperative details, flap survival, surgical complications, and outcomes. The cases were divided into two groups in "low-risk" (American Society of Anesthesiologists [ASA] I and II) or "high-risk" (ASA III and IV) as per the preoperative medical status classified according to the ASA score of physical status. Despite the significantly high prevalence of hypertension, peripheral artery disease, diabetes, obesity, and smoking status in the "high-risk" group (p < 0.05), there was no significant difference in the rate of surgical or medical complications, in operative times regarding overall as well as different flap entities, flap failures, need for revision surgery, or hospital length of stay between the two patient groups during our 3-months follow-up period (p > 0.05). In this study, free flap reconstruction in medically compromised patients was not associated with higher rates of revision surgeries, overall complication rates, or surgery-related costs. Complex microsurgical free flap reconstruction can therefore also be advocated in patients with high preoperative risk constellation.


O-GlcNAcylation Is Essential for Autophagy in Cardiomyocytes.
Since both O-GlcNAcylation and autophagy sense intracellular nutrient level, the alteration of those two pathways plays substantial roles in the progression of heart failure. Hence, determining the relationship between O-GlcNAcylation and autophagy is imperative to understand, prevent, and treat heart failure. However, the mechanism on how O-GlcNAcylation regulates autophagy in the heart is poorly investigated. In this study, we demonstrated that O-GlcNAcylation is required for autophagy in cardiomyocytes by utilizing an O-linked β-N-acetylglucosamine transferase (OGT) cardiomyocyte-specific knockout mouse model for the first time. We also identified that OGT might regulate the initiation of autophagy in cardiomyocytes through promoting the activity of ULK1 by O-GlcNAcylation. In conclusion, our findings provide new insights into the molecular mechanisms underlying heart dysfunction and benefit the development of treatments for heart failure.


Development of behavioural automaticity by extended Pavlovian training in an insect.
The effect of repetitive training on learned actions has been a major subject in behavioural neuroscience. Many studies of instrumental conditioning in mammals, including humans, suggested that learned actions early in training are goal-driven and controlled by outcome expectancy, but they become more automatic and insensitive to reduction in the value of the outcome after extended training. It was unknown, however, whether the development of value-insensitive behaviour also occurs by extended training of Pavlovian conditioning in any animals. Here we show that crickets Gryllus bimaculatus that had received minimal training to associate an odour with water (unconditioned stimulus, US) did not exhibit conditioned response (CR) to the odour when they were given water until satiation before the test, but those that had received extended training exhibited CR even when they were satiated with water. Further pharmacological experiments suggested that octopamine neurons, the invertebrate counterparts of noradrenaline neurons, mediate US value signals and control execution of CR after minimal training, but the control diminishes with the progress of training and hence the CR becomes insensitive to US devaluation. The results suggest that repetitive sensory experiences can lead to a change from a goal-driven response to a more automatic one in crickets.


Time-lapse videomicrographic observations of blastocyst hatching in cattle.
Morphological changes of cultured bovine blastocysts during hatching were observed using time-lapse videomicrography in order to investigate the patterns of the hatching process that occurred in the blastocysts and to determine whether the hatching patterns differed between blastocysts developed from fresh and cryopreserved embryos. Compacted morulae (CMs) were collected from superovulation-treated Japanese Black and Holstein dairy cattle and cultured in a medium in a CO(2) culture chamber equipped with an inverted microscope at 38.5 C. Images of resultant blastocysts during the period from blastocoel formation to completion of hatching were taken at 4-sec intervals by a CCD color camera connected to an inverted microscope and recorded by a time-lapse video cassette recorder. In blastocysts developed from fresh CMs, hatching was found to begin with protrusion of trophectoderm cells from zonae pellucidae at the expanded stage. Protrusion of the cells occurred in any site of the trophectoderm. After protrusion, a large or small slit was formed in the zona pellucida in all blastocysts as a result of blastocyst expansion or enlargement of the protrusion. Then, blastocysts completely escaped from the zona pellucida through the slit in the state of expansion. From these findings, the hatching patterns of cattle blastocysts could be classified into 5 types. In blastocysts developed from frozen-thawed CMs, the hatching pattern and length of time needed for hatching are similar to those in blastocysts developed from fresh CMs. In addition, the pregnancy rate of recipients following transfer of frozen-thawed CMs (52.4%) did not differ from that of recipients following transfer with fresh CMs (58.3%). These results suggested that the quality of frozen-thawed cattle embryos is comparable to that of fresh embryos and that there could be a relationship between the hatching pattern of blastocysts and the viability of embryos after transfer.


Effect of estradiol on estrogen receptor expression in rat uterine cell types.
In rodent uterus, both up- and down-regulation of estrogen receptor alpha (ERalpha) messenger ribonucleic acid (mRNA) and protein levels by estradiol has been demonstrated; however, it is not known which of the uterine compartments (endometrial epithelium, stroma, myometrium) respond to estradiol with autoregulation of ERalpha. The purpose of the present study was to investigate and compare the kinetics and cell type-specific effects of estradiol on uterine ERalpha expression in immature and adult rats. Ovariectomized female rats were injected s.c. with sesame oil or estradiol-17beta. Uteri were collected and analyzed for changes in ERalpha mRNA using RNase protection assays (RPA) and in situ hybridization using radiolabeled probes specific for ERalpha. Immunohistochemical analysis was performed with a polyclonal antibody specific to ERalpha. Expression of ERalpha in the uterine epithelial cells decreased at 3 and 6 h after estradiol administration to immature and adult rats, respectively. At 24 h, ERalpha mRNA levels in the immature and mature rat uterus were higher than pretreatment levels but returned to baseline by 72 h. Pretreatment with cycloheximide did not block the 3-h repressive effect of estradiol, suggesting that the estradiol-induced decrease in ERalpha mRNA occurs independent of new protein synthesis. A decrease in ERalpha mRNA and protein was also observed in uterine epithelia at 3 and 6 h after an estradiol injection to immature and adult rats, and intensity of both the in situ hybridization signal and the immunostaining in the epithelium increased at 24 and 72 h. However, the periluminal stromal cells in the adult uterus and the majority of stromal cells of the immature uterus appeared to have increased ERalpha expression. The results indicate that down-regulation of ERalpha in the epithelia and up-regulation of stromal ERalpha play a role in early events associated with estradiol-induced cell proliferation of the uterine epithelia.


[The evaluation of 3DFT time-of-flight MR-angiography versus angiography in the study of carotid atheromatous lesions with a review of the literature].
In 37 patients suspected of having a stroke 71 carotid bifurcations were explored by MR-angiography and by digital angiography the reference technique. A 3D sequence was acquired with the time-of-flight technique, using a transmitter-receiver cranial coil, followed by a strictly receiver Helmoltz coil on a 1 Tesla magnet. Two examiners evaluated the carotid bifurcations and measured the degree of stenosis in terms of diameters, according to the north american symptomatic carotid endarterectomy trial (NASCET). Five classes were established: class 1: normal; class 2: 1 to 29%; class 3: 30 to 69%; class 4: 70 to 99% and class 5: thrombosis. The results obtained in the determination of classes were identical with both coils: the coefficient of correlation with straight angiography were 0.973 with the cranial coil and 0.966 with the Helmoltz coil. Five stenoses were overestimated and classified as Class 3 instead of Class 2. The five stenoses greater than 70% (Class 4) showed a signal-void area at their level, due to severe dephasing induced by turbulences. Finally, there was a false-negative image of occlusion: the high-intensity signal of the thrombus was mistaken for one of flow. The data of our study were in accordance with the excellent results obtained by several authors in the literature, which makes it possible for us to propose this type of examination as a novel mean of investigating bifurcations of carotid arteries. Provided a strict technique is applied, and in addition to carotid bifurcation the Willis' circle and the cerebral parenchyma are explored, MR-angiography can complete the results of Doppler-echo. Standard arteriography could then be reserved to surgical patients and to those with discordant results of MR-arteriography and Doppler echo systems.


Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico.
Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.


A prospective randomised trial of two treatments for wound seroma after breast surgery.
Seroma formation is a recognised complication of breast surgery causing wound pain and discomfort. It was hypothesised that daily aspiration of symptomatic seromas that formed after breast surgery would encourage flap adherence to the chest wall, thereby allowing swifter resolution of seroma. Thirty-six patients undergoing mastectomy and/or axillary clearance who formed seroma post operatively, were randomised into two groups either having daily aspiration of seroma or aspiration as required by patient symptoms. The daily aspiration required significantly more attendances for aspiration (P<0.005) and the time from surgery to final aspiration was not reduced. Daily aspiration of symptomatic seroma did not result in swifter resolution.


Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine?
A double-blind randomized crossover design trial of carbamazepine (CBZ) and oxcarbazepine (OCBZ) was performed with 48 in-patients with epilepsy. All were stabilized on polytherapy including CBZ and had at least two seizures per week. CBZ was replaced by the trial medication. Each trial period started with a titration, followed by a 12-week steady state. Concomitant medications were kept constant during the trial. The criteria for assessment were seizure fit frequency and severity; tolerability; hematology and blood chemistry; plasma levels of antiepileptic drugs; EEG; cardiovascular parameters; and treatment preference. The following differences regarding OCBZ were detected: 9% reduction of the total number of seizures, with a significant reduction of tonic-clonic (20%) and tonic (31%) seizures; increased alertness and concentration ability in five patients; an allergic skin reaction with CBZ that completely disappeared in two patients while receiving OCBZ; an increase of valproate and phenytoin plasma levels in a number of patients, probably caused by reduced enzyme induction; a slight but significant reduction of serum Na, not causing clinical symptoms; less seizures than in the CBZ period in 25 patients (52%); and a preference for OCBZ in 23 patients (48%). We consider OCBZ at least as effective as CBZ with a slightly better tolerability. In severe cases, the wider therapeutic window might improve seizure control.


[Granulo-monocyte growth factors. Their value in pneumonologic oncologic practice].
Granulo-monocytic growth factors are important members of the family of growth factors which alter the biological response. These factors are glycoproteins and are hormones regulating the production of haematopoietic cells and show their adaptation to possible needs. There are four which are currently well recognised; they are now grouped collectively under the term colony-stimulating factor and of these two, GM-CSF and G-CSF are available thanks to genetic engineering and have reached the stage of therapeutic trials. It is essentially the treatment of solid tumours which should lead to the most profound changes in the current management of cytotoxic drugs because they may allow an increase of the dose and a shortening of the duration of the phase of neutropenia and thus the infection risk. In therapeutic pneumonology they would be able to be used as an adjuvant to chemotherapy in small cell cancers and available in protocols using polychemotherapy with a risk of marrow suppression, indeed even permitting the practice of intensified chemotherapy regimes with or without the support of bone marrow graft. However the clinical experience acquired using growth factors remains limited and is almost exclusively restricted to the haematological domain. Although the secondary effects appear tolerable their harmlessness--and notably the absence of a stimulating effect on tumour growth--remains to be shown before extension of their use will lead to any changes of therapeutic strategies.


Does a multidisciplinary diabetes group education visit improve patient outcomes?
Diabetes is a significant and growing public health concern, and patient education is the primary approach for self-management. The objective of this study is to assess the impact of a single session diabetes group education intervention. The design is a one-group pretest/posttest evaluation. Participants were adult outpatients with diabetes who attended a single session group education visit and volunteered to participate in the study. Survey questions include the Single Item Literacy Screener and diabetes knowledge questions. The survey was mailed and collected before the group visit. Diabetes knowledge was collected immediately after the group visit and again by telephone one to four months later. Hemoglobin A1c (HbA1c), lipids, and blood pressure were collected from the patient electronic medical record before and, where available, three months after the group visit. Data analysis includes descriptive statistics and Students t-testing to determine pre- and posttest differences of diabetes knowledge and physiological markers. Thirty-eight adult outpatients participated in the study. Nearly half responded that they never needed to have someone help with written medical materials. There was a significant increase from pretest to immediate posttest diabetes knowledge scores (N = 3; M = 5.58 to M = 7.53 out of 10), t(38) = -5.217, p = < 0.001 and a significant decrease in HbA1c from pretest to posttest group education (M = 9.16 to M = 8.52), t(27) = 2.185, p = .038. A single session diabetes group education visit is effective in increasing patients' diabetes knowledge and decreasing HbA1c levels.


Reactions of Ruthenium Complexes Containing Pentatetraenylidene Ligand.
Two ruthenium acetylide complexes [Ru]-C≡C-C≡C-C(OR)(C3 H5 )2 (2, R=H and 2 a, R=CH3 ; [Ru]=Cp(PPh3 )2 Ru) each with two cyclopropyl rings were synthesized from TMS-C≡C-C≡C-C(OH)(C3 H5 )2 (1; TMS=trimethylsilyl). Treatments of 2 and 2 a with allyl halide in the presence of KPF6 afforded the vinylidene complexes 3 and 3 a, respectively. When NH4 PF6 was used, instead of KPF6 , additional ring-opening reaction took place on one of the three-membered ring. Treatment of [Ru]Cl with 1,3-butadiyne (6), bearing an epoxide ring, afforded acetylide complex 7 with a furyl ring. Treatment of 2 a with Ph3 CPF6 presumably afforded pentatetraenylidene complex {[Ru]=C=C=C=C=C(C3 H5 )2 }[PF6 ] (10), which was not isolated. Additions of various alcohols in a solution of 10 generated a number of disubstituted allenylidene complexes {[Ru]=C=C=C(OR)-C=C(C3 H5 )2 }[PF6 ] (11). Treatment of 11 with K2 CO3 afforded the acetylide complex 12 bearing a carbonyl group, characterized by single X-ray diffraction analysis. Addition of a primary amine to 10 caused cleavage of the farthermost C=C bond and several allenylidene complexes {[Ru]=C=C=C(Me)(NHR)}[PF6 ] (18) were isolated.


Resource-limited, collaborative pilot intervention for chronically homeless, alcohol-dependent frequent emergency department users.
We introduced case management and homeless outreach to chronically homeless, alcohol-dependent, frequent emergency department (ED) visitors using existing resources. We assessed the difference in differences of ED visits 6 months pre- and postintervention using a prospective, nonequivalent control group trial. Secondary outcomes included changes in hospitalizations and housing. The differences in differences between intervention and prospective patients and retrospective controls were -12.1 (95% CI = -22.1, -2.0) and -12.8 (95% CI = -26.1, 0.6) for ED visits and -8.5 (95% CI = -22.8, 5.8) and -19.0 (95% CI = -34.3, -3.6) for inpatient days, respectively. Eighteen participants accepted shelter; no controls were housed. Through intervention, ED use decreased and housing was achieved.


Invasive fungal infections in the intensive care unit.
Invasive fungal infections, especially candidemia and systemic candidiasis, have become a major cause of morbidity and mortality in the last few decades. This comes in parallel with the major advances made in intensive care. Patients who are critically ill, in medical or surgical ICUs are especially at risk for CANDIDA infections. Invasive candidiasis accounts for up to 15 to 30% of all nosocomial infections in critically ill patients. Management of these severe infections has been challenging due to a lack of rapid and reliable diagnostic methods, leading to delays in initiating appropriate antifungal therapy. However, some notable improvements have been made in diagnostics with improved culturing methods, rapid species identification, and detection of fungemia with newer antigen assays. Newer classes of antifungals have recently become available with broader antifungal activity, fewer drug-drug interactions, and improved tolerability when compared with the older antifungal agents. Despite these advancements, the mortality rates associated with candidiasis remain excessively high, with an overall mortality in the range of 30 to 50% and an attributable mortality of ~30%. In addition to this high case-fatality rate, candidemia is also associated with a substantial economic burden, primarily due to an extended length of stay. Strategies to evaluate either the prevention, early diagnosis, or initiation of appropriate therapy should yield both clinical and socioeconomic benefits.


Inhibition of voltage-gated sodium channels by emulsified isoflurane may contribute to its subarachnoid anesthetic effect in beagle dogs.
Volatile anesthetics, in addition to their general anesthesia action, have been proven to produce regional anesthetic effect in various animal models. The major aim of this study was to examine whether emulsified isoflurane (EI) could also produce subarachnoid anesthesia and to investigate its possible mechanism. Beagle dogs were randomly assigned into 5 groups (n = 6/group): intrathecally receiving 1% lidocaine 0.1 mL/kg, 30% intralipid 0.1 mL/kg (control), or 8% EI at doses of 0.05, 0.075, or 0.1 mL/kg, respectively. Consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. The effect of EI on voltage-gated Na channel was recorded from isolated spinal neurons of rats, using the whole-cell patch-clamp technique. Inhibition of peak sodium currents and effect of EI on Na channel gating were analyzed. Emulsified isoflurane produced subarachnoid anesthesia in a dose-dependent manner, and at the dose of 0.1 mL/kg, the effect of 8% EI was similar to 1% lidocaine. Sodium channel currents were inhibited by EI at clinically relevant concentrations, with the IC50 (median inhibitory concentration) at 0.69 ± 0.08 mM. Voltage activation of Na channels was positive, shifted by isoflurane at the concentration of 0.77 mM, and V½ of activation (voltage for half-maximal activation) shifted from -12.4 ± 2.7 mV to -7.3 ± 2.3 mV (P < 0.01). Emulsified isoflurane produced dose-dependent subarachnoid anesthesia, and this effect might be mediated by inhibition of EI on voltage-gated Na channels in the spinal cord.


Robotic Rehabilitation Game Design for Chronic Stroke.
This study investigates games intended for use with an upper-limb exoskeleton robot operated unilaterally and bilaterally. Games are evaluated in terms of usability and preference for stroke survivors. Game design considerations relating to the human to machine interface, are also discussed. Ten hemiparetic stroke survivors completed 12 90-minute sessions using an upper-limb robotic exoskeleton unilaterally and bilaterally. During the sessions subjects played seven different games designed for rehabilitation. At the conclusion of their sessions subjects completed an 83-question survey. Subjects preferred static games to dynamic games. Preferred games elicited greater effort. Intermediate goals in addition to ultimate goals should be set with both static and dynamic games such that even with the patient's limited range of motion, speed, or coordination, the game should be playable and provide a sense of accomplishment to the patient. Marking the games' ultimate goals that can be accomplished only by healthy subjects, such as range of motion and workspace, provide references and encouragement to the patient for improving motor control and performance through the process of playing the game.


Manganese-enhanced MRI to evaluate neurodegenerative changes in a rat model of kainic acid-induced excitotoxicity.
Manganese-enhanced magnetic resonance imaging (MEMRI) has been used to detect brain activity based on the ability of active neurons to take up manganese ions through calcium channels. Kainic acid (KA), an analog of excitotoxic glutamate, can elicit selective neuronal death in the brains of rodents, of which the pathological changes partially mimic neurodegeneration in the central nervous system. We used in vivo MEMRI to evaluate neurodegenerative changes in an excitotoxicity model induced by KA in rats. Adult Sprague-Dawley rats (220-250 g) were injected with either KA or saline into the right lateral ventricle. Precontrast and postcontrast MEMRI sessions were obtained. Region of interest (ROI) analyses were performed on both injected (saline and KA) and contralateral (normal) sites in the hippocampal area. All brains were evaluated histologically following MEMRI. Analysis of percentage change in ROI intensities of T1-weighted fluid-attenuated inversion-recovery MR images in the hippocampal area revealed a significant difference between the KA-injected (ipsilateral) and contralateral sites (P = 0.008), whereas no significant difference was observed between the saline-injected and contralateral sites. Furthermore, there was a significant difference between ipsilateral sites of the saline-treated and KA-treated groups (P = 0.026). The histological results supported these findings. MEMRI is a simple and useful in vivo method for detecting neurodegenerative changes due to excitotoxicity in the rat brain. The development of a manganese-based contrast agent that can be safely used in humans is warranted to investigate neurological disorders.


[Unilateral auditory hallucinations due to left temporal lobe ischemia: a case report].
Unilateral auditory hallucinations are a rare lateralization phenomenon experienced in one ear or from one direction. We recently encountered a 63-year-old right-handed man who developed transient unilateral auditory hallucinations associated with pure word deafness. The patient had a past history of myocardial infarction, lung cancer and aortic aneurysm, but no previous psychiatric or convulsive disorders. About six months before admission, he developed right hemiparesis and motor aphasia caused by a hemorrhagic left parietal infarct. These symptoms gradually improved over three weeks. Two days before admission, he suddenly lost the ability to understand spoken words. He concurrently experienced auditory hallucinations arising from the right anterior direction. On admission, he was very embarrassed to simple verbal commands. He was unable to comprehend spoken words and repeat speech, although he could fairly follow written commands. Confrontation naming, reading aloud, comprehension, spontaneous writing remained relatively unaffected, although he occasionally made paraphasic errors. He could distinguish environmental sounds such as a telephone ringing or running water. After gradual improvement of his auditory incomprehension, he began to describe auditory hallucinations of verbal, musical and elementary types. He was fully aware of the hallucinatory nature of his experience, and took some notes. Two days before admission, from the right anterior side of his head he heard a familiar radio announcer reporting news about the earthquake in Osaka Prefecture and the recommended places of refuge. After similar experiences over several days, he repetitively heard a familiar Japanese traditional song from the right side, which was followed by elementary auditory hallucinations such as a car engine and a siren. These symptoms spontaneously disappeared after nine days. Besides his auditory hallucinations, visual hallucinations and illusional emotion were temporarily present. The Wechsler adult intelligence scale revealed a verbal IQ of 91 and a performance IQ of 100. Pure tone audiometry revealed bilateral, mild peripheral sensorineural hearing loss. Brainstem auditory evoked potentials were unrevealing. The EEG showed slow activities in the left temporoparietal region. Magnetic resonance imaging of the brain failed to reveal any relevant abnormalities except for an old hemorrhagic parietal infarct. The SPECT with Tc99m-HMPAO, however, showed reduced blood flow in the left temporal lobe including the first temporal convolution as well as in the left parietal lobe. Based on the SPECT findings, unilateral auditory hallucinations in our patient are considered to have resulted from the left temporal lobe ischemia. Our case indicates that unilateral auditory hallucinations may have a clinicoanatomical correlation with contralateral temporal lobe lesions.


A preclinical trial of perventricular pulmonary valve implantation: Pericardial versus aortic porcine valves mounted on self-expandable stent.
Perventricular pulmonary valve implantation (PPVI) of a xenograft valve can be a less invasive technique that avoids cardiopulmonary bypass in patients who require pulmonary valve replacement. We compared the hemodynamics, durability, and histologic changes between two different xenogenic valves (pericardial vs. aortic valve porcine xenografts) implanted into the pulmonary valve position using a PPVI technique and evaluated the safety and efficacy of PPVI as a preclinical study. In 18 sheep, pericardial (group porcine pericardial [PP], n = 9) or aortic valve (group porcine aortic valve [PAV], n = 9) xenogenic porcine valves manufactured as a stented valve were implanted using a PPVI technique. The porcine tissues were decellularized, alpha-galactosidase treated, fixed with glutaraldehyde after space-filler treatment, and detoxified to improve durability. Hemodynamic and immunohistochemical studies were performed after the implantation; radiologic and histologic studies were performed after a terminal procedure. All stented valves were positioned properly after the implantation, and echocardiography and cardiac catheterization demonstrated good hemodynamic state and function of the valves. All the anti-α-Gal IgM and IgG titers were below 0.3 optical density. Computed tomography of extracted valves demonstrated no significant differences in the degree of calcification between the two groups (P = .927). Microscopic findings revealed a minimal amount of calcification and no significant infiltration of macrophage or T-cell in both groups, regardless of the implantation duration. The PPVI is a feasible technique. Both stented valves made of PP and PAV showed no significant differences in hemodynamic profile, midterm durability, and degree of degenerative dystrophic calcification.


A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components.
Leptospirosis is a neglected zoonosis, caused by pathogenic spirochetes bacteria of the genus Leptospira. The molecular mechanisms of leptospirosis infection are complex, and it is becoming clear that leptospires express several functionally redundant proteins to invade, disseminate, and escape the host's immune response. Here, we describe a novel leptospiral protein encoded by the gene LIC13086 as an outer membrane protein. The recombinant protein LIC13086 can interact with the extracellular matrix component laminin and bind plasminogen, thus possibly participating during the adhesion process and dissemination. Also, by interacting with fibrinogen and plasma fibronectin, the protein LIC13086 probably has an inhibitory effect in the fibrin clot formation during the infection process. The newly characterized protein can also bind molecules of the complement system and the regulator C4BP and, thus, might have a role in the evasion mechanism of Leptospira. Taken together, our results suggest that the protein LIC13086 may have a multifunctional role in leptospiral pathogenesis, participating in host invasion, dissemination, and immune evasion processes.


A Technique for 360-Degree Rigid Sternal Fixation with Sternal Plates and Wire Cerclage.
Sternal instability after cardiac surgery can lead to poor bony healing, as well as deep sternal wound infections and mediastinitis. Rigid plate fixation is associated with greater stability and fewer complications compared with wire cerclage, however, rigid plate fixation alone lacks posterior stability of the sternum and may be less effective in morbidly obese or osteoporotic patients. This article describes a surgical technique of combined rigid plate fixation and wire cerclage that provides 360-degree stabilization for sternotomies in high-risk patients. We employed this technique in 40 patients with no incidence of deep sternal wound infection.


Delivery outcomes of patients with pre-eclampsia at 27 - 34 weeks' gestation at Tygerberg Hospital, Cape Town, South Africa: A retrospective observational study.
Obstetricians are cognisant of the serious nature of hypertensive disorders in pregnancy. Despite a 17% overall reduction in maternal deaths in South Africa between 2011 and 2016, there was a 14% increase in deaths due to hypertension. Delivery is the only known cure for pre-eclampsia, but the question regarding the safest route of delivery remains difficult to answer. To determine the success rate of induction of labour (IoL) in patients with early-onset pre-eclampsia with severe features (EOPES) before 34 weeks' gestation. Furthermore, the data from the induction group were compared with those of the caesarean delivery (CD) groups where patients were not eligible for IoL. Additional objectives were to identify variables that could influence the success rate, to determine whether any delivery method was associated with increased morbidity, to assess the short-term maternal and neonatal outcomes, and to make recommendations for future decision-making regarding delivery for women with EOPES. In this single-institution retrospective observational study, all cases in which a decision for delivery was made before 34 weeks 0 days of gestation (or the infant's birthweight was ≤2 000 g with uncertain gestation) at Tygerberg Hospital, Cape Town, between 1 January and 30 June 2017 were identified from the electronic birth register. The cohort fitting the inclusion criteria was subdivided into IoL and CD groups. From a total of 3 938 deliveries, 168 patients met the inclusion criteria. IoL was indicated in 55 cases, resulting in 20 vaginal deliveries (VDs) (36%) and 35 CDs (64%). The remaining 113 patients were not candidates for IoL; of these, 89 required emergency CDs and 24 had semi-elective CDs. In the IoL group with abnormal umbilical artery Dopplers (UADs) there was 1 VD, and 4 CDs were performed for fetal compromise. Of cases with an estimated fetal weight (EFW) ≤3rd centile, emergency CD was required in 24 (65%), and 8 (22%) were considered for IoL, in 6 of which CD was required. Of the EOPES population, 36% had successful IoL that culminated in VD. VD was more likely to occur with fetal growth appropriate for gestational age. The likelihood of CD increased if the UAD was abnormal, if the EFW was ≤3rd centile or if eclampsia was present. The decision to induce should be considered carefully in these circumstances.


Effect of spatial design and thermal oxidation on apatite formation on Ti-15Zr-4Ta-4Nb alloy.
Apatite formation on the surface of titanium and its alloys is effective for inducing osteoconductivity when implanted in bony defects. The aim of this study was to investigate the effects of thermal oxidation on apatite formation in macro-grooves on Ti-15Zr-4Ta-4Nb. Thermal oxidation at 500 and 600 degrees C in air led to modification of the Ti-15Zr-4Ta-4Nb surface to rutile phase titanium oxide. Ti-15Zr-4Ta-4Nb thermally oxidized at 500 degrees C in air showed no changes in metallographic structure, but not at 600 degrees C. After soaking in a simulated body fluid for 7days, the formation of apatite could be observed on the internal surfaces of macro-grooves 500mum deep and wide on Ti-15Zr-4Ta-4Nb thermally oxidized at 500 and 600 degrees C in air. These results indicate the potential for osteoconductivity of Ti-15Zr-4Ta-4Nb without changing its metallographic structure, by fabricating only the macro-grooves, i.e., spatial design, and by performing thermal oxidation at 500 degrees C.


Young adults' knowledge of the strength of different alcoholic beverages.
Providing information about the strength of different alcoholic beverages is a common component of alcohol abuse prevention programs. However, little is known about drinkers' knowledge of the strength of different alcoholic beverages. In the present study, 113 young adult drinkers responded to a questionnaire concerning the alcohol content of different types of malt beverages (beers, malt liquors), wines, fortified wines (port, sherry), and distilled spirits. The results indicated rates of correct responses well below 50 percent for each type of alcoholic beverage, with a substantial proportion of subjects either overestimating or underestimating alcohol content. Not a single subject reported correct alcohol content values for all four beverage types. There was a trend towards less accurate estimates of the alcohol content of strength were less accurate than those of men. The results are discussed in terms of prevention of alcohol abuse.


Controlled acid hydrolysis of colominic acid under microwave irradiation.
The hydrolysis of colominic acid under microwave irradiation was studied and compared with traditional heating methods. The microwave irradiation has several advantages over the heating method in the hydrolysis of colominic acid: (a) products with higher degrees of polymerization are obtained, (b) less lactone byproducts are observed, and (c) the hydrolytic rate is much faster. These advantages are probably due to the microwave effect. Oligosialic acids as the products of the acid hydrolysis of polysialic acid with conventional heating methods were fully lactonized, especially under the conditions of higher temperature and stronger acid.


More to 3-D vision than meets the eye.
Does self-motion affect object recognition? Researchers have long studied how 3-D objects are recognized from different points of view, but have disregarded the observers' own movement by keeping them motionless. A recent study by Simons et al. shows that self-motion cannot be ignored, as it changes the way that objects are recognized.


The cardiomyopathy of overload: a hypothesis.
Progressive deterioration of the failing heart is now recognized to be a major cause of disability and death in patients with congestive heart failure. It appears that although the normal human heart functions for at least 90-100 years, overload-induced hypertrophy shortens the heart's life span to about 5 years. This accelerated deterioration of the failing heart can be viewed as a cardiomyopathy of overload in which chronic overloading causes changes in the myocardial cells that, while increasing cell mass, reduce their long-term viability. Although the pathogenesis of this putative cardiomyopathy remains poorly understood, chronic energy starvation and altered myocardial cell growth and composition appear to be contributing factors. Preferential expression of fetal isoforms of key muscle proteins, which accompanies accelerated growth of the overloaded heart, may contribute to this cardiomyopathy. The hypothesis that the cardiomyopathy of overload is due in part to a growth abnormality is supported by evidence that deterioration of the failing heart is slowed by the converting enzyme inhibitors, which may attenuate important effects of angiotensin II to stimulate cellular growth.


Intracellular location of carbonate dehydratase (carbonic anhydrase) in leaf tissue.
Two proteins which have carbonate dehydratase (carbonic anhydrase, EC 184.108.40.206) activity were shown to be in the chloroplasts and in the cytosol of leaves of Brassica chinensis, Spinacia oleracea, and in variegated leaves of Tradescantia albiflora and Hedera canariensis. The chloroplastic enzyme is smaller than the one in the cytosol, as it runs farther on gradient polyacrylamide gels. It was separated from the other by isolation of chloroplasts of Brassica and Spinacia on sucrose density gradients; approximately half of the total activity was in the chloroplasts.


Toxicity studies of octahydro-tetramethyl-naphthalenyl-ethanone (OTNE) administered dermally to F344/NTac rats and B6C3F1/N mice.
Octahydro-tetramethyl-naphthalenyl-ethanone (OTNE) is a fragrance ingredient that is formed as a mixture of isomers with a basic unsaturated alkyl cyclic ketone structure. The main isomer is 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (β-isomer). Two other predominant isomers within the mixture are 1-(1,2,3,4,6,7,8,8a-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (α-isomer) and 1-(1,2,3,5,6,7,8,8a-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone (γ-isomer). OTNE is used as a perfume ingredient in soap, shampoo, cologne, liquid detergent compounds, and malodor-reducing compounds. Male and female F344/NTac rats and B6C3F1/N mice were administered OTNE (greater than 92.3% pure with respect to the 3 prominent isomers) dermally for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and rat and mouse peripheral blood erythrocytes. (Abstract Abridged).


Thrombopoietin signalling in physiology and disease.
Thrombopoietin (TPO) is a key physiological regulator of steady-state megakaryocytopoiesis, the process of megakaryocyte production and maturation that ultimately results in the formation of platelets. Ten years have passed since the purification and cloning of TPO and extensive studies of the activities of recombinant forms of the cytokine, as well as analyses of genetically modified mice lacking or over-expressing TPO or its receptor c-Mpl, have defined the role of TPO in megakaryocytopoiesis as well as uncovered unanticipated actions. Biochemical analyses have identified a number of signalling pathways, including the Jak/signal transducers and activators of transcription (STAT) and Ras cascades that transmit signals from the activated cell surface receptor complex to the cell nucleus resulting in changes in gene expression and the biological responses of TPO-stimulated cells. Since TPO is the most potent known stimulus of platelet production in vivo, the evaluation of this cytokine for clinical use in the treatment of thrombocytopenia is being actively pursued and recent studies have suggested that aberrations in the TPO signalling pathway may contribute to disease.


Macrolide-resistant Shigella sonnei.
Shigella sonnei UCN59, isolated during an outbreak of S. sonnei in January 2007, was resistant to azithromycin (MIC 64 mg/L). The isolate contained a plasmid-borne mph(A) gene encoding a macrolide 2 -phosphotransferase that inactivates macrolides. Emergence of the mph(A) gene in S. sonnei may limit usefulness of azithromycin for treatment of shigellosis.


Basilar artery embolism. Clinical syndrome and neuroradiologic patterns in patients without permanent occlusion of the basilar artery.
The objective of this study was to clarify the clinical and radiologic features, risk factors, and prognosis of basilar embolism without permanent basilar artery occlusion. Forty-five patients (mean age, 59 years) with basilar artery embolism participated in the study. Patients with basilar artery occlusion were excluded. The Glasgow Coma Scale (GCS) score on admission was < 7 in five patients, 7 to 12 in 11 patients, and > 12 in 29 patients. Etiologic factors were cardiac arrhythmia (17 patients), vertebral artery occlusion (12 patients), cervical spine trauma (4 patients), embolism following angiography (2 patients), and surgery (1 patient). MRI was performed in 17 patients and CT in 39 patients. Radiologic examinations were initially normal in 14 patients and remained normal in three patients. Final infarct localization was the thalamus (36 patients), cerebellum (20 patients), posterior cerebral artery territory (21 patients), midbrain (12 patients), and pons (8 patients). Eight to 12 weeks after stroke 12 patients were without clinical signs (Glasgow Outcome Scale [GOS] 1), 15 patients had minor neurologic deficits (GOS 2), 10 were severely disabled (GOS 3), and eight patients had died (GOS 5). Outcome correlated with GCS on admission (p < 0.0001) and with the number of ischemic lesions (p = 0.0001). The typical syndrome is an acute loss of consciousness followed by multiple brainstem symptoms. Usually, clinical symptoms improve rapidly and, in some patients, completely. Compared with basilar occlusion, basilar embolism has a relatively low mortality and outcome is frequently excellent.


Antifungal effect and pore-forming action of lactoferricin B like peptide derived from centipede Scolopendra subspinipes mutilans.
The centipede Scolopendra subspinipes mutilans has been a medically important arthropod species by using it as a traditional medicine for the treatment of various diseases. In this study, we derived a novel lactoferricin B like peptide (LBLP) from the whole bodies of adult centipedes, S. s. mutilans, and investigated the antifungal effect of LBLP. LBLP exerted an antifungal and fungicidal activity without hemolysis. To investigate the antifungal mechanism of LBLP, a membrane study with propidium iodide was first conducted against Candida albicans. The result showed that LBLP caused fungal membrane permeabilization. The assays of the three dimensional flow cytometric contour plot and membrane potential further showed cell shrinkage and membrane depolarization by the membrane damage. Finally, we confirmed the membrane-active mechanism of LBLP by synthesizing model membranes, calcein and FITC-dextran loaded large unilamellar vesicles. These results showed that the antifungal effect of LBLP on membrane was due to the formation of pores with radii between 0.74nm and 1.4nm. In conclusion, this study suggests that LBLP exerts a potent antifungal activity by pore formation in the membrane, eventually leading to fungal cell death.


The evolution of a new cell type was associated with competition for a signaling ligand.
There is presently a very limited understanding of the mechanisms that underlie the evolution of new cell types. The skeleton-forming primary mesenchyme cells (PMCs) of euechinoid sea urchins, derived from the micromeres of the 16-cell embryo, are an example of a recently evolved cell type. All adult echinoderms have a calcite-based endoskeleton, a synapomorphy of the Ambulacraria. Only euechinoids have a micromere-PMC lineage, however, which evolved through the co-option of the adult skeletogenic program into the embryo. During normal development, PMCs alone secrete the embryonic skeleton. Other mesoderm cells, known as blastocoelar cells (BCs), have the potential to produce a skeleton, but a PMC-derived signal ordinarily prevents these cells from expressing a skeletogenic fate and directs them into an alternative developmental pathway. Recently, it was shown that vascular endothelial growth factor (VEGF) signaling plays an important role in PMC differentiation and is part of a conserved program of skeletogenesis among echinoderms. Here, we report that VEGF signaling, acting through ectoderm-derived VEGF3 and its cognate receptor, VEGF receptor (VEGFR)-10-Ig, is also essential for the deployment of the skeletogenic program in BCs. This VEGF-dependent program includes the activation of aristaless-like homeobox 1 (alx1), a conserved transcriptional regulator of skeletogenic specification across echinoderms and an example of a "terminal selector" gene that controls cell identity. We show that PMCs control BC fate by sequestering VEGF3, thereby preventing activation of alx1 and the downstream skeletogenic network in BCs. Our findings provide an example of the regulation of early embryonic cell fates by direct competition for a secreted signaling ligand, a developmental mechanism that has not been widely recognized. Moreover, they reveal that a novel cell type evolved by outcompeting other embryonic cell lineages for an essential signaling ligand that regulates the expression of a gene controlling cell identity.


Arteriovenous fistula after fibular osteotomy leading to recurrent haemarthroses in a total knee replacement.
We present a patient with an arteriovenous fistula of the peroneal artery acquired after a left dome tibial osteotomy with midshaft fibular osteotomy. He had subsequently had a total knee replacement on that side. The arteriovenous malformation was only diagnosed when he represented with symptoms and signs of venous hypertension with sterile recurrent haemarthroses in the left knee. Percutaneous obliteration of the fistula, by a combination of coil embolisation and balloon occlusion, cured the symptoms.


Evolution of Mutator transposable elements across eukaryotic diversity.
Mutator-like elements (MULEs) are a significant superfamily of DNA transposons on account of their: (i) great transpositional activity and propensity for insertion in or near gene sequences, (ii) their consequent high mutagenic capacity, and, (iii) their tendency to acquire host gene fragments. Consequently, MULEs are important genetic tools and represent a key study system for research into host-transposon interactions. Yet, while several studies have focused on the impacts of MULEs on crop and fungus genomes, their evolution remains poorly explored. We perform comprehensive bioinformatic and phylogenetic analyses to address currently available MULE diversity and reconstruct evolution for the group. For this, we mine MULEs from online databases, and combine search results with available transposase sequences retrieved from previously published studies. Our analyses uncover two entirely new MULE clades that contain elements almost entirely restricted to arthropod hosts, considerably expanding the set of MULEs known from this group, suggesting that many additional MULEs may await discovery from further arthropod genomes. In several cases, close relationships occur between MULEs recovered from distantly related host organisms, suggesting that horizontal transfer events may have played an important role in the evolution of the group. However, it is apparent that MULEs from plants remain separate from MULEs identified from other host groups. MULE structure varies considerably across phylogeny, and TIR length is shown to vary greatly both within and between MULE groups. Our phylogeny suggests that MULE diversity is clustered in well-supported groups, typically according to host taxonomy. With reference to this, we make suggestions on how MULE diversity can be partitioned to provide a robust taxonomic framework. Our study represents a considerable advance in the understanding of MULE diversity, host range and evolution, and provides a taxonomic framework for the classification of further MULE elements that await discovery. Our findings also raise a number of questions relating to MULE biology, suggesting that this group will provide a rich avenue for future study.


Modularity and cognition.
Modularity is a concept central to cognitive science, and Fodor's analysis of cognitive modularity in his book The Modularity Of Mind has been widely influential - but also widely misunderstood. It is often claimed that the possession of some or other system-property is a necessary condition for that system to be modular in Fodor's sense, but Fodor made it clear that he was not proposing a definition of modularity, nor proposing any necessary conditions for the applicability of the term. He was simply suggesting a number of system properties that are typical of modular systems. I argue that it is nevertheless possible to derive a useful definition of modularity from the kinds of arguments put forward by Fodor: A cognitive system is modular when and only when it is domain-specific. Given any such proposed module, the other features of modularity discussed by Fodor should be dealt with as empirical issues: for each feature (innateness, for example), it is an empirical question whether or not the proposed module has that feature.


Flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways.
Citrus platymamma hort. ex Tanaka (Rutaceae family) has been widely used in Korean folk medicine for its wide range of medicinal benefits including an anticancer effect. In the present study, we aimed to investigate the molecular mechanism of the anticancer effects of flavonoids isolated from Citrus platymamma (FCP) on AGS cells. FCP treatment significantly inhibited AGS cell growth in a dose‑dependent manner. Furthermore, FCP significantly increased the percentage of cells in the sub-G1 phase (apoptotic cell population), and apoptosis was confirmed by Annexin V double staining. Chromatin condensation and apoptotic bodies were also noted in the FCP-treated AGS cells. Moreover, immunoblotting results showed that FCP treatment significantly decreased the expression of procaspase-3, -6, -8 and -9, and PARP and increased cleaved caspase-3, cleaved PARP and the Bax/Bcl-xL ratio in a dose-dependent manner. In addition, the phosphorylation of AKT was significantly decreased, whereas extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) were significantly increased in the FCP-treated AGS cells. Taken together, the cell death of AGS cells in response to FCP was mitochondrial-dependent via modulation of the PI3K/AKT and MAPK pathways. These findings provide new insight for understanding the mechanism of the anticancer effects of FCP. Thus, FCP may be a potential chemotherapeutic agent for the treatment of gastric cancer.


Progress of selective catalytic reduction denitrification catalysts at wide temperature in carbon neutralization.
With the looming goal of carbon neutrality and increasingly stringent environmental protection policies, gas purification in coal-fired power plants is becoming more and more intense. To achieve the NOx emission standard when coal-fired power plants are operating at full load, wide-temperature denitrification catalysts that can operate for a long time in the range of 260-420°C are worthy of study. This review focuses on the research progress and deactivation mechanism of selective catalytic reduction (SCR) denitration catalysts applied to a wide temperature range. With the increasing application of SCR catalysts, it also means that a large amount of spent catalysts is generated every year due to deactivation. Therefore, it is necessary to recycle the wide temperature SCR denitration catalyst. The challenges faced by wide-temperature SCR denitration catalysts are summarized by comparing their regeneration processes. Finally, its future development is prospected.


Physical Activity Behavior During the COVID-19 Outbreak in Individuals with Type 2 Diabetes: Role of Social Support and Other Covariates.
This study was performed to investigate whether social support and other psychological predictors were associated with physical activity during the prolonged social isolation due to the coronavirus disease 2019 outbreak in Iran. This cross-sectional study was performed on 494 individuals with type 2 diabetes (T2D) in a diabetes specialty clinic. The questionnaire package comprised five parts, including sociodemographic and clinical characteristics, physical activity level, diabetes-specific social support, feelings of isolation, and diabetes-related distress. Clinical and hemoglobin A1c data were obtained from electronic medical records. Descriptive statistics, Pearson's chi-square test, and multivariable logistic regressions were conducted to analyze the data. Approximately 71% of the participants participated in low/insufficient levels of physical activity. The participants who received support from family/friends (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.47 - 2.74), diabetes care team (OR = 1.42; 95% CI: 1.15 - 1.77), and neighbors (OR = 1.53; 95% CI: 1.20 - 2.08) were more likely to have sufficient physical activity than those who did not receive these supports. There was also an association between physical activity behavior with feelings of isolation and diabetes distress. This study points to the importance of social support as an amplifier mechanism for the maintenance of physical activity behavior in individuals with T2D during critical times.


[The status and changes of soil nutrients in rhizosphere of cultivated Atractylodes lancea].
To find the status and changes of the soil nutrients in rhizosphere of Atractylodes lancea. Total nitrogen (total N), available K, available P, organic matter (ORG), available nitrogen and pH in rhizosphere soil of the wild growing A. lancea in 3 sites, MS, LT and MFS, and the cultivated ones with different ages in LT were detected. The contents of total nitrogen (total N), available K, available P, organic matter (ORG), available nitrogen and pH value in rhizosphere soil were significant different between MS, LT and MFS (P < 0.01). The results of the 6 detected parameters in MS were the lowest, in MFS were the highest and in LT were in the middle. The total N, ORG and available N in the cultivated A. lancea were lower than that in the wild ones (P < 0.01) and available P and pH value in the cultivated A. lancea were higher than that in wild ones (P < 0.01) and there was no difference in available K between the wild and cultivated ones in LT (P > 0.05); 3 available P in rhizosphere soil of the two years old A. lancea were higher than of the one year old A. lancea (P < 0.01) and there were no difference of total N, ORG, available N, available K and pH value in rhizosphere soil of A. lancea between one year and two years plant (P > 0.05). It is indicated that the growth of A. lancea in Mt. Mao is faced nutrient stress.


Copper-mediated controlled radical ring-opening polymerization (RROP) of a vinylcycloalkane.
This investigation reports controlled ring-opening polymerization of a vinylcyclopropane via copper-mediated atom transfer radical polymerization which leads to predominantly 1,5 ring-opening polymerization.


A new method to recover L-tyrosine from E. coli fermentation broth.
Although the production of L-tyrosine by recombinant Escherichia coli has been widely reported, L-tyrosine recovery from the fermentation broth has been rarely reported. Methods to recover L-tyrosine from the broth after alkaline lysis of the bacterial cells have been described. However, the broth becomes viscous and dark following cell lysis, making further extraction and purification difficult. Here, a new method for L-tyrosine extraction and purification from the fermentation broth without the lysis of bacteria is reported. First, acids, rather than bases, were used to dissolve L-tyrosine in the broth without causing lysis of the bacterial cells. E. coli cells in the broth were then removed through centrifugation. Activated carbon was then used to decolorize the supernatant containing L-tyrosine. Finally, sodium hydroxide was added to the clarified L-tyrosine solution for isoelectrocrystallization. L-tyrosine was obtained after filtration and drying. The recovery yield of L-tyrosine was 92%, and the purity was >98.5%, indicating high efficiency of the new method of L-tyrosine recovery from fermented broth. Furthermore, the method provides a reference for the extraction of guanosine, inosine, hypoxanthine, and other biological fermentation products.


Evaluation of functionality of cochlear outer hair cells in patients with retinitis pigmentosa and in their relatives.
Hearing functionality was studied in 36 patients with retinitis pigmentosa (R P) and 29 of their relatives. These patients were defined as having bilateral normal hearing on the basis of tonal-threshold audiometric and acoustic-immittance tests. The transiently evoked otoacoustic emissions (T E O A Es) were studied in these normal hearing patients. T E O A Es represent an extremely sensitive method to study the functionality of the outer hair cells of the organ of Corti. When the values of T E O A E amplitude, intensity, and frequency in R P patients and in their relatives were compared with those in control subjects, they were found to be significantly reduced. The T E O A Es were clearly pathological in 52.8% of patients with R P and in 24.1% of their relatives. During embryologic development, there is one transitory axoneme in the outer hair cells of the organ of Corti; this transitory axoneme is important for the organization of the stereocilia. Axonemes are found in mature hair cells, including photoreceptors. The alteration of cochlear outer hair cells in a high percentage of patients with R P and in some of their relatives corroborates the hypothesis that, in some instances, retinitis pigmentosa may be due to a structural anomaly of the ciliated cells.


Ultrasound fusion imaging system in neurology practice.
The ultrasound fusion imaging (UFI) system is a new promising imaging modality that combines live ultrasound investigations with preregistered CT, MRI, or PET images. In this study, we want to present our initial experience with the new method that combines the transcranial color-coded sonography (TCCS) in different insonation planes and the 3T-weighted MRI cerebral images. The study validates the diagnostic capabilities of the system to detect different normal cerebral structures in healthy volunteers. In the present paper, we also discuss the advantages of US fusion imaging technology and its clinical applications in Neurology.


Noradrenaline modulation of calcium channels in single smooth muscle cells from rabbit ear artery.
1. Whole-cell recordings of voltage-gated Ca2+ current in single smooth muscle cells from rabbit ear artery were obtained with 110 mM-Ba2+ as charge carrier. 2. Noradrenaline (NA, 1-20 microM) produced a sustained increase in the dihydropyridine-sensitive L-type Ca2+ current, ranging up to 3-fold in some cells. The dihydropyridine-resistant T-type Ca2+ current was not affected. 3. The time and voltage dependence of activation and inactivation of the L-type current were not significantly changed during NA modulation. 4. The NA-induced increase in L-current was enhanced in magnitude and consistency by the inclusion of 200 microM-GTP in the pipette (internal) solution. 5. The effect of NA on L-current was not abolished by pre-treatment with prazosin, phentolamine or propranolol, suggesting that it is not mediated by alpha- or beta-adrenoceptors. 6. Phenylephrine (5 microM) was ineffective as an agonist, while adrenaline was approximately equipotent to NA. In these respects, the pharmacology of L-current modulation resembles that of 'gamma'-adrenergic receptors (Hirst & Nield, 1980). 7. NA modulation of L-type Ca2+ channels may be particularly important in promoting sympathetic vasoconstriction in resistance vessels where Ca2+ stores are relatively poorly developed and where NA-evoked contractions are very sensitive to organic Ca2+ channel antagonists.


[Effects of temperature extremes on daily mortality in Castile-La Mancha (Spain): trends from 1975 to 2003].
To determine time trends and the geographical distribution of mortality trigger temperature thresholds due to extreme temperatures in Castile-La Mancha (central Spain) between 1975 and 2003. The analysis was divided into three periods (1975-1984, 1985-1994 and 1995-2003) for each province of the region. Daily mortality due to organic causes (dependent variable) was modelled using autoregressive integrated moving average (ARIMA) procedures. The resulting residual series was related to the maximum temperature series grouped in 2 degrees C intervals to obtain a threshold temperature for cold or heat when the residuals rose significantly (p<0,05) above the mean residual mortality value of the corresponding study period. Mortality trigger temperature thresholds decreased over time in Castile- La Mancha. In Toledo, the trigger temperature diminished from 40 degrees C to 38 degrees C. In Cuenca and Guadalajara, threshold temperatures for heat events were obtained in the last few decades but not in the first. These thresholds varied from the 92nd percentile in Cuenca to the 98th percentile in Albacete in the last decade. No threshold temperatures for cold spells were observed in any province or period. Castile-La Mancha registered an upward trend in the relationship between high temperatures and mortality, probably due to population aging. This trend could have been influenced by the increased frequency of extremely hot days. Prevention plans should be periodically reviewed.


Mild Water Stress of Phaseolus vulgaris Plants Leads to Reduced Starch Synthesis and Extractable Sucrose Phosphate Synthase Activity.
Mild water stress, on the order of -1.0 megapascals xylem water potential, can reduce the rate of photosynthesis and eliminate the inhibition of photosynthesis caused by O(2) in water-stress-sensitive plants such as Phaseolus vulgaris. To investigate the lack of O(2) inhibition of photosynthesis, we measured stromal and cytosolic fructose-1,6-bisphosphatase, sucrose phosphate synthase, and partitioning of newly fixed carbon between starch and sucrose before, during, and after mild water stress. The extractable activity of the fructose bisphosphatases was unaffected by mild water stress. The extractable activity of SPS was inhibited by more than 60% in plants stressed to water potentials of -0.9 megapascals. Water stress caused a decline in the starch/sucrose partitioning ratio indicating that starch synthesis was inhibited more than sucrose synthesis. We conclude that the reduced rate of photosynthesis during water stress is caused by stomatal closure, and that the restriction of CO(2) supply caused by stomatal closure leads to a reduction in the capacity for both starch and sucrose synthesis. This causes the reduced O(2) inhibition and abrupt CO(2) saturation of photosynthesis.


Suppressor cell function in respiratory allergy. Modulation by aminophylline and isoproterenol.
The status of suppressor cells in patients with allergic rhinitis or asthma was studied. This latter group showed absent concanavalin A (ConA)-inducible suppressor cell function as measured by proliferative responses to pokeweed mitogen (PWM) and decreased function as measured by responses to phytohemagglutinin (PHA) or ConA. Patients with rhinitis showed values intermediate between normals and asthmatics. Similarly, preincubation in medium enhanced proliferative responses in normal and rhinitis patients but not in asthmatics, suggesting an absence of a short-lived suppressor cell population in the latter group. Suppressor cell function correlated negatively with log10 of serum IgE concentrations. Theophylline-sensitive suppressor cell numbers were slightly decreased in rhinitis patients and significantly so in asthmatics (p less than 0.01). In vitro preincubation of normal lymphocytes with aminophylline or isoproterenol (10 micrograms/ml) enhanced subsequent proliferative responses to PWM. Little enhancement was observed with cells from rhinitis patients, and actual depression was seen with cells from asthmatics, suggesting abnormal immunomodulatory effects of cyclic-AMP active drugs in this group of patients.


Conserved Pattern and Potential Role of Recurrent Deletions in SARS-CoV-2 Evolution.
SARS-CoV-2 continues adapting to human hosts during the current worldwide pandemic since 2019. This virus evolves through multiple means, such as single nucleotide mutations and structural variations, which has brought great difficulty to disease prevention and control of COVID-19. Structural variation, including multiple nucleotide changes like insertions and deletions, has a greater impact relative to single nucleotide mutation on both genome structures and protein functions. In this study, we found that deletion occurred frequently in not only SARS-CoV-2 but also in other SARS-related coronaviruses. These deletions showed obvious location bias and formed 45 recurrent deletion regions in the viral genome. Some of these deletions showed proliferation advantages, including four high-frequency deletions (nsp6 Δ106-109, S Δ69-70, S Δ144, and Δ28271) that were detected in around 50% of SARS-CoV-2 genomes and other 19 median-frequency deletions. In addition, the association between deletions and the WHO reported variants of concern (VOC) and variants of interest (VOI) of SARS-CoV-2 indicated that these variants had a unique combination of deletion patterns. In the spike (S) protein, the deletions in SARS-CoV-2 were mainly in the N-terminal domain. Some deletions, such as S Δ144/145 and S Δ243-244, have been confirmed to block the binding sites of neutralizing antibodies. Overall, this study revealed a conservative regional pattern and the potential effect of some deletions in SARS-CoV-2 over the whole genome, providing important evidence for potential epidemic control and vaccine development. IMPORTANCE Mutations in SARS-CoV-2 were studied extensively, while only the structure variations on the spike protein were discussed well in previous studies. To study the role of structural variations in virus evolution, we described the distribution of structure variations on the whole genome. Conserved patterns were found of deletions among SARS-CoV-2, SARS-CoV-2-like, and SARS-CoV-like viruses. There were 45 recurrent deletion regions (RDRs) in SARS-CoV-2 generated through the integration of deleted positions. In these regions, four high-frequency deletions parallelly appeared in multiple strains. Furthermore, in the spike protein, the deletions in SARS-CoV-2 were mainly in the N-terminal domain, blocking the binding sites of some neutralizing antibodies, while the structural variations in SARS-related coronavirus were mainly in the N-terminal domain and receptor binding domain. The receptor binding domain is highly related to hosting recognition. The deletions in the receptor binding domain may play a role in host adaption.