Determinants and trends in dental expenditures in the adult US population: Medical Expenditure Panel Survey 1996-2006.
To estimate dental expenditures in 2006, to analyse dental expenditures by potential explanatory factors for 2006 and to explore trends in dental expenditures from 1996-2006. Medical Expenditure Panel Survey (MEPS) data were used. T-tests and analysis of variance were used to test for significance. Multivariable linear regression analysis was conducted to identify independent predictors of dental expenditures. The trend analysis was conducted for the 11-year period, 1996-2006, on adults aged 25 years and older. Expenditures were inflation adjusted to 2006 dollars using the annual average Consumer Price Index. Data were analysed using the MEPS query tool and SASv9.2. In the 2006 MEPS sample, 8,001 adults had dental expenditures and when weighted represented about 93 million non-institutionalised adult US civilians. The mean dental expenditures for this weighted sample were $611 (sd 1,309), median $233 (inter-quartile range 466). As expected, in 2006, dental expenditures increased with age. Those adults who reported their self-perceived health status as 'excellent' were observed to have lowest dental expenditures in this category. After adjusting for other variables in the multivariable linear regression analysis of dental expenditures, age, race/ethnicity, income, geographic location, perceived health status and dental insurance coverage remained significant. Dental expenditures for 2006 were $611 (mean) and $233 (median). The time-trend showed substantial but non-uniform annual changes in real dental expenditures between 1996 and 2006.


[Combined injuries of bile ducts and hepatic artery branches in cholecystectomy].
Results of treatment of 25 patients with combined injuries of bile ducts and the common hepatic artery in performing cholecystectomy were studied. In 19 (73.1%) patients the injuries were noted during open and in 7 (26.9%) patients during laparoscopic cholecystectomy. The patients needed multimodal strategy of treatment with reference to the time when the diagnosis was made and to the characteristics of clinical course. Positive results of treatment were obtained in 84.6% of cases, lethality made up 3.9%.


MiR-335 functions as a tumor suppressor and regulates survivin expression in osteosarcoma.
Previous studies have shown that miR-335 plays an anti-tumor role in several types of cancer. However, whether it is able to regulate the tumorigenesis of osteosarcoma (OS) has not been fully investigated. The present study was designed to study its potential role in regulating apoptosis of OS cells. The expression of miR-335 in a total of 18 paired OS tumor tissues and adjacent non-cancerous tissues was measured by Real-time PCR, and its different expression in OS cell lines was also measured. The effect of miR-335 on apoptosis was measured by MTT assay, caspase-3 activity assay and TUNEL assay. The effect of survivin inhibition on apoptosis of OS cells was determined by MTT assay and western blot. Luciferase reporter assay and western blot were conducted to confirm the relationship between miR-335 and the 3'UTR of survivin mRNA. MiR-335 expression was found to be significantly downregulated in OS tumor tissues and OS cell lines. Overexpression of miR-335 led to decreased cell viability and increased apoptosis. MiR-335 directly targeted the 3'UTR of survivin mRNA and suppressed survivin gene expression, and inhibition of survivin exhibited similar effects to miR-335 overexpression. MiR-335 might function as a tumor suppressor in OS, and downregulation of miR-335 in OS cells contributes to the decreased apoptotic potential of OS cells through derepression of survivin.


Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.
This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.


Spontaneous regression of colon carcinoma.
Apparent spontaneous regression of advanced colon carcinoma has been reported in 7 patients. This is a very rare event, and the circumstances accounting for this are elusive.


[Acquired toxoplasmosis with cerebral involvement and subsequent hearing loss].
In immunocompetent patients the postnatally acquired toxoplasmosis is usually a mild or asymptomatic disease. CNS manifestations are rare, e.g. in patients with HIV infection or in patients with other types of immunosuppression. We report on a 9-year old healthy boy, who was hospitalized after one week with subfebrile temperatures and headache with clinical signs of encephalitis and unilateral deafness. We diagnosed a toxoplasmosis and treated the patient with pyrimethamine and sulfadiazine. While most of the signs and symptoms disappeared rapidly the deafness persisted.


A prospective multicenter study on the safety of a pacemaker with automatic energy control: influence of the electrical factor on chronic stimulation threshold. PEACE Investigators.
The effectiveness and safety of a pacemaker with automatic control of capture was evaluated in 162 patients followed at 27 Spanish centers. The aim of our prospective, multicenter, and randomized trial was to determine the relationship between the voltage output of the pulse generator and the stimulation threshold. We randomized 162 patients (107 men, mean age 75 +/- 12 years). We implanted a ventricular pacemaker model Regency SR+ or SC+ with Pacesetter's low polarization bipolar leads Membrane E 1450. The patients were randomized to receive Autocapture or not; group I (81 patients) Autocapture On, pulse output automatically adjusted and group II (81 patients) Autocapture Off, fixed output parameters (3.9 V, 0.37 ms). We performed a 6-month follow-up measuring stimulation threshold by means of the VARIO test and Autocapture test, evoked response signal, and R wave signal. The mean R wave was 15.77 +/- 3.5 mV at the end of the follow-up for group I, and 14.91 +/- 6.8 mV for group II (P = NS). The measured evoked response at the end of the follow-up was 9.25 mV in Group I and 8.48 mV in Group II (P = NS). The stimulation threshold was not different between groups. The current density created with the voltage and pulse width used in this study (< or = 3.9 V and 0.37 ms) at the tip of this electrode during the maturation process had no influence on the development of the chronic detection and stimulation thresholds.


In vitro evaluation of dissolution behavior for a colon-specific drug delivery system (CODES) in multi-pH media using United States Pharmacopeia apparatus II and III.
United States Pharmacopeia dissolution apparatus II (paddle) and III (reciprocating cylinder) coupled with automatic sampling devices and software were used to develop a testing procedure for acquiring release profiles of colon-specific drug delivery system (CODES) drug formulations in multi-pH media using acetaminophen (APAP) as a model drug. System suitability was examined. Several important instrument parameters and formulation variables were evaluated. Release profiles in artificial gastric fluid (pH 1.2), intestinal fluid (pH 6.8), and pH 5.0 buffer were determined. As expected, the percent release of APAP from coated core tablets was highly pH dependent. A release profile exhibiting a negligible release in pH 1.2 and 6.8 buffers followed by a rapid release in pH 5.0 buffer was established. The drug release in pH 5.0 buffer increased significantly with the increase in the dip or paddle speed but was inversely related to the screen mesh observed at lower dip speeds. It was interesting to note that there was a close similarity (f2 = 80.6) between the release profiles at dip speed 5 dpm and paddle speed 100 rpm. In addition, the release rate was reduced significantly with the increase in acid-soluble Eudragit E coating levels, but lactulose loading showed only a negligible effect. In conclusion, the established reciprocating cylinder method at lower agitation rates can give release profiles equivalent to those for the paddle procedure for CODES drug pH-gradient release testing. Apparatus III was demonstrated to be more convenient and efficient than apparatus II by providing various programmable options in sampling times, agitation rates, and medium changes, which suggested that the apparatus III approach has better potential for in vitro evaluation of colon-specific drug delivery systems.


Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice: Involvement of TGF-β1/Smads Signaling Pathway.
Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease (COPD), its underlying mechanisms were not clear until now. We aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract (CSE). Twenty SPF C57BL/6 mice were randomly divided into PBS control group, COPD model group, low-dose berberine group and high-dose berberine group, 5 mice in each group. The neutrophils and macrophages were examined by Wright's staining. The levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The expression levels of TGF-β1, Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western blotting. It was found that CSE increased the number of inflammation cells in BALF, elevated lung inflammation scores, and enhanced the TGF-β1/Smads signaling activity in mice. High-dose berberine restrained the alterations in the COPD mice induced by CSE. It was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD mice. TGF-β1/Smads signaling pathway might be involved in the mechanism. These findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation.


Revision of the Genus Coriplites Foissner, 1988 (Ciliophora: Haptorida), with Description of Apocoriplites nov. gen. and Three New Species.
The genera Coriplites Foissner, 1988 and Apocoriplites nov. gen., which differ by the number of dorsal brush rows (3 vs. 2), belong to the haptorid Litostomatea and have a distinct feature in common: they lack oral extrusomes. Based on three new species, the diagnosis of the genus Coriplites is amended to include the wide spacing of the brush dikinetids and the heavily refractive cortical granules. Using standard methods, we redescribe C. terricola Foissner, 1988 and describe three new species: C. grandis (from swamp soil of Australia), C. proctori (from tanks of bromeliads in Jamaica), and Apocoriplites lajacola (from granitic rook-pools in Venezuela). Species are distinguished by the nuclear apparatus (a single nodule vs. two nodules with a micronucleus in between), the body size (<100 μm vs. >100 μm), the number of ciliary rows, and details of the dorsal brush (isostichad vs. heterostichad). In over 1,000 soil samples, only C. terricola has been found in all main biogeographic regions, while the other species have been found only at their type locality, i.e., in the southern hemisphere, where the genus possibly originated.


Reviewing the relationship between neoliberal societies and nature: implications of the industrialized dominant social paradigm for a sustainable future.
How a society relates to nature is shaped by the dominant social paradigm (DSP): a society's collective view on social, economic, political, and environmental issues. The characteristics of the DSP have important consequences for natural systems and their conservation. Based on a synthesis of academic literature, we provide a new gradient of 12 types of human-nature relationships synthesized from scientific literature, and an analysis of where the DSP of industrialized, and more specifically, neoliberal societies fit on that gradient. We aim to answer how the industrialized DSP relates to nature, i.e., what types of human-nature relationships this DSP incorporates, and what the consequences of these relationships are for nature conservation and a sustainable future. The gradient of human-nature relationships is based on three defining characteristics: (1) a nature-culture divide, (2) core values, and (3) being anthropocentric or ecocentric. We argue that the industrialized DSP includes elements of the anthropocentric relationships of mastery, utilization, detachment, and stewardship. It therefore regards nature and culture as separate, is mainly driven by instrumental values, and drives detachment from and commodification of nature. Consequently, most green initiatives and policies driven by an industrialized and neoliberal DSP are based on economic incentives and economic growth, without recognition of the needs and limits of natural systems. This leads to environmental degradation and social inequality, obstructing the path to a truly sustainable society. To reach a more ecocentric DSP, systemic changes, in addition to individual changes, in the political and economic structures of the industrialized DSP are needed, along with a change in values and approach toward nature, long-term sustainability, and conservation.


MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer.
We used the paclitaxel-resistant human small cell lung cancer subline PC-6/TAX1-1, selected from PC-6 cells by paclitaxel, to test whether MRP7/ABCC10 (ABCC10) confers paclitaxel resistance. We found that gene expression of both ABCB1/MDR1 (ABCB1) and ABCC10 was higher in PC-6/TAX1-1 cells than in PC-6 cells. The expression levels of ABCC10 showed a significant inverse correlation with paclitaxel sensitivity (r = 0.574; P < 0.05) in 17 non-small cell lung cancer (NSCLC) cells unlike the expression levels of ABCB1. Pretreatment with the ABCC10 inhibitor sulfinpyrazone altered the sensitivity to paclitaxel in ABCC10-expressing NSCLC cells, concomitant with increased intracellular paclitaxel accumulation. These findings suggest that expression of the ABCC10 gene is induced by paclitaxel and that ABCC10 confers paclitaxel resistance by enhancing the efflux for paclitaxel. To confirm this hypothesis, we tested the effect on paclitaxel cytotoxicity of decreasing the expression of ABCC10 by small interfering RNA and found that this enhanced paclitaxel cytotoxicity in NCI-H23 cells concomitant with increased intracellular paclitaxel accumulation. These data indicate that ABCC10 may be one of the biomarkers for paclitaxel resistance in NSCLC.


Peripheral and central primitive neuroectodermal tumors. A nosologic concept seeking a consensus.
The term primitive neuroectodermal tumor is widely used in the literature for a group of small, round-cell tumors in the central and sympathetic nervous systems and soft tissues as well as a specific diagnostic term for individual neoplasms; however, the contention that these various clinicopathologic entities (neuroblastoma, medulloblastoma, and peripheral neuroepithelioma) are histogenetically related is an unproved hypothesis. Morphologic, cytogenetic, immunohistochemical, biochemical, and in vitro studies have established phenotypic similarities among these putatively related neoplasms whether they originate in the brain, adrenal gland, or soft tissues. Because one tumor resembles another in terms of its phenotypic expression, that does not necessarily imply a common histogenesis. This point has been made by previous investigators. The purpose of this review is to evaluate and discuss the present status of our understanding and some of the controversial aspects of this enigmatic category of neoplasms, mainly occurring in children, known as the primitive neuroectodermal tumors.


Hexvix blue light fluorescence cystoscopy--a promising approach in diagnosis of superficial bladder tumors.
Nowadays, Hexvix blue light cystoscopy (BLC) represents an increasingly acknowledged diagnostic method for patients with bladder cancer. The aim of our study was to establish the place of this procedure in superficial bladder tumors diagnosis and to compare it with standard white light cystoscopy (WLC). Between December 2007 and January 2008, WLC and BLC were performed in 20 cases. Transurethral bladder resection (TURB) was performed for all apparent detected lesions. The patients diagnosed with superficial bladder tumors have been followed-up after 3 months by WLC and BLC. The control group included the same number of consecutive patients with superficial bladder tumors, diagnosed only by WLC, which underwent the same treatment and follow-up protocol as the study group. WLC identified 30 suspicious lesions (28 pathologically confirmed), while BLC identified 41 apparent tumors (39 pathologically confirmed). So, from the total number of 40 tumors with positive histology, WLC correctly diagnosed 70% of them, with a rate of 6.7% false-positive results, while BLC diagnosed 97.5%, however presenting a 4.9% rate of false-positive results. 17 cases of the study group diagnosed with superficial bladder tumors were followed. The tumor recurrence rate after 3 months was 5.9% for the study group and 23.5% for the control group. Hexvix fluorescence cystoscopy is a valuable diagnostic method, with considerably better results by comparison to WLC. The improved diagnostic may have a significant impact upon the recurrence rate.


Genetic characterization of Toxoplasma gondii isolates from pigs in China.
Toxoplasma gondii genetic diversity varies in different geographical regions. In South America, T. gondii isolates are highly diverse, whereas in North America and Europe, the parasite is highly clonal, with 3 distinct lineage types (I, II, III). However, little is known of the T. gondii genotypes in the People's Republic of China. Because pork is considered the principal meat source for T. gondii infection in China, we conducted a survey to determine the prevalence and genetic diversity of this parasite in pigs from central China. In total, 434 DNA samples were extracted from the hilar lymph nodes of sick pigs in Hubei and Henan provinces in central China, and 34 were T. gondii B1 gene-positive. These T. gondii -positive DNA samples were typed at 10 genetic markers, including 9 nuclear loci, i.e., SAG1, SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and an apicoplast locus Apico. Of these, 16 isolates could be genotyped with complete data for all loci. Two genotypes were present; one was the clonal type I lineage and the other was previously identified as a widespread lineage from many hosts in China. These results indicate that these 2 genotypes may be the major lineages in China. This is the first report of genetic typing of T. gondii isolates from pigs in central China. The results have implications for the prevention and control of T. gondii infections in humans and other animals.


Overall and cause-specific mortality in Korean patients with inflammatory bowel disease: A hospital-based cohort study.
Limited data are available regarding mortality from inflammatory bowel disease in non-Caucasian populations. Herein, we evaluated overall and cause-specific mortality in a hospital-based cohort of Korean inflammatory bowel disease patients. We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups. During the mean 9-year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97-1.94) in Crohn's disease and 0.73 (0.58-0.91) in ulcerative colitis. In Crohn's disease, female sex, age < 30 years at diagnosis, disease duration > 10 years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever-use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age ≥ 30 years at diagnosis, disease duration ≤ 5 years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47). The overall mortality tended to be higher in Crohn's disease patients than in the general population; it was slightly lower in ulcerative colitis patients than in the general population.


Fitness self-perception and Vo2max in firefighters.
Firefighters work at maximal levels of exertion. Fitness for such duty requires adequate aerobic capacity (maximum oxygen consumption [Vo2max]). Aerobic fitness can both improve a worker's ability to perform and offer resistance to cardiopulmonary conditions. Inactive firefighters have a 90% greater risk of myocardial infarction than those who are aerobically fit. Participants (101 firefighters) completed a questionnaire that asked them to rank their fitness level from 0 to 7; e.g., Level 0 was low fitness: "I avoid walking or exertion, e.g., always use elevator, drive whenever possible." The level of activity rating increased to Level 7: "I run over 10 miles per week or spend 3 hours per week in comparable physical activity." Each participant then completed two measures of Vo2max: a 5-minute step test and a submaximal treadmill test. There was no association between the firefighters' self-perception of their level of fitness and their aerobic capacity as measured by either step test or submaximal treadmill. Because of the critical job demands of firefighting and the negative consequences of inadequate fitness and aerobic capacity, periodic aerobic capacity testing with individualized exercise prescriptions and work--community support may be advisable for all active-duty firefighters.


A Native Mass Spectrometry-Based Assay for Rapid Assessment of the Empty:Full Capsid Ratio in Adeno-Associated Virus Gene Therapy Products.
Adeno-associated virus (AAV)-based gene therapy is a rapidly developing field, requiring analytical methods for detailed product characterization. One important quality attribute of AAV products that requires monitoring is the amount of residual empty capsids following downstream processing. Traditionally, empty and full particles are quantified via analytical ultracentrifugation as well as anion exchange chromatography using ultraviolet or fluorescence detection. Here, we present a native mass spectrometry-based approach to assess the ratio of empty to full AAV-capsids without the need for excessive sample preparation. We report the rapid determination of the relative amount of empty capsids in AAV5 and AAV8 samples. The results correlate well with more conventional analysis strategies, demonstrating the potential of native mass spectrometry for the characterization of viral particles.


Robust 3D breast reconstruction based on monocular images and artificial intelligence for robotic guided oncological interventions.
Breast cancer is a global public health concern. For women with suspicious breast lesions, the current diagnosis requires a biopsy, which is usually guided by ultrasound (US). However, this process is challenging due to the low quality of the US image and the complexity of dealing with the US probe and the surgical needle simultaneously, making it largely reliant on the surgeon's expertise. Some previous works employing collaborative robots emerged to improve the precision of biopsy interventions, providing an easier, safer, and more ergonomic procedure. However, for these equipment to be able to navigate around the breast autonomously, 3D breast reconstruction needs to be available. The accuracy of these systems still needs to improve, with the 3D reconstruction of the breast being one of the biggest focuses of errors. The main objective of this work is to develop a method to obtain a robust 3D reconstruction of the patient's breast, based on RGB monocular images, which later can be used to compute the robot's trajectories for the biopsy. To this end, depth estimation techniques will be developed, based on a deep learning architecture constituted by a CNN, LSTM, and MLP, to generate depth maps capable of being converted into point clouds. After merging several from multiple points of view, it is possible to generate a real-time reconstruction of the breast as a mesh. The development and validation of our method was performed using a previously described synthetic dataset. Hence, this procedure takes RGB images and the cameras' position and outputs the breasts' meshes. It has a mean error of 3.9 mm and a standard deviation of 1.2 mm. The final results attest to the ability of this methodology to predict the breast's shape and size using monocular images.Clinical Relevance- This work proposes a method based on artificial intelligence and monocular RGB images to obtain the breast's volume during robotic guided breast biopsies, improving their execution and safety.


Thermal tolerance breadths among groundwater crustaceans living in a thermally constant environment.
The climate variability hypothesis assumes that the thermal tolerance breadth of a species is primarily determined by temperature variations experienced in its environment. If so, aquatic invertebrates living in thermally buffered environments would be expected to exhibit narrow thermal tolerance breadths (stenothermy). We tested this prediction by studying the thermal physiology of three isopods (Asellidae, Proasellus) colonizing groundwater habitats characterized by an annual temperature amplitude of less than 1°C. The species responses to temperature variation were assessed in the laboratory using five physiological variables: survival, locomotor activity, aerobic respiration, immune defense and concentrations of total free amino acids and sugars. The three species exhibited contrasted thermal physiologies, although all variables were not equally informative. In accordance with the climate variability hypothesis, two species were extremely sensitive even to moderate changes in temperature (2°C) below and above their habitat temperature. In contrast, the third species exhibited a surprisingly high thermal tolerance breadth (11°C). Differences in response to temperature variation among Proasellus species indicated that their thermal physiology was not solely shaped by the current temperature seasonality in their natural habitats. More particularly, recent gene flow among populations living in thermally constant yet contrasted habitats might explain the occurrence of eurytherm species in thermally buffered environments.


Spa therapy (balneotherapy) relieves mental stress, sleep disorder, and general health problems in sub-healthy people.
To investigate the relieving effects of hot spring balneotherapy on mental stress, sleep disorder, general health problems, and women's health problems in sub-healthy people, we recruited 500 volunteers in sub-health in Chongqing, and 362 volunteers completed the project, including 223 in the intervention group and 139 in the control group. The intervention group underwent hot spring balneotherapy for 5 months, while the control group did not. The two groups took questionnaire investigation (general data, mental stress, emotional status, sleep quality, general health problems, as well as some women's health problems) and physical examination (height, weight, waist circumference, blood pressure, blood lipid, blood sugar) 5 months before and after the intervention, respectively. After intervention, sleep disorder (difficulty in falling asleep (P = 0.017); dreaminess, nightmare suffering, and restless sleep (P = 0.013); easy awakening (P = 0.003) and difficulty in falling into sleep again after awakening(P = 0.016); and mental stress (P = 0.031) and problems of general health (head pain (P = 0.026), joint pain(P = 0.009), leg or foot cramps (P = 0.001), blurred vision (P = 0.009)) were relieved significantly in the intervention group, as compared with the control group. While other indicators (fatigue, eye tiredness, limb numbness, constipation, skin allergy) and women's health problems (breast distending pain; dysmenorrhea, irregular menstruation) were relieved significantly in the self-comparison of the intervention group before and after intervention (P < 0.05), but showed no statistically significant difference between two groups (P > 0.05). All indications (except bad mood, low mood, and worry or irritability) in the intervention group significantly improved, with effect size from 0.096 to 1.302. Multiple logistic regression analysis showed that the frequency, length, and location of balneotherapy in the intervention group were the factors influencing emotion, sleep, and health condition (P < 0.05). Relief of insomnia, fatigue, and leg or foot cramps was greater in old-age group than in young-aged group (P < 0.05). Physical examination found that waist circumferences in women of various ages under 55 years were significantly reduced in the intervention group (P < 0.05), while that in men did not significantly change (P > 0.05). Spa therapy (balneotherapy) relieves mental stress, sleep disorder, general health, and reduces women's waist circumferences in sub-healthy people.


Prospective Evaluation of Aspergillus fumigatus-Specific IgG in Patients With Cystic Fibrosis.
In Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is Aspergillus fumigatus (Af). Af diseases are associated with significant morbidity and mortality. The most common clinical picture caused by Af is allergic bronchopulmonary aspergillosis (ABPA), triggered by an immunological reaction against Af. Af bronchitis and invasive aspergillosis rarely occur in CF as a result of spore colonization and germination. Since pulmonary mycoses and exacerbations by other pathogens overlap in clinical, radiological, and immunological characteristics, diagnosis still remains a challenge. The search for reliable, widely available biomarkers for Af diseases is therefore still an important task today. Af-specific IgG m3 is broadly available. Sensitivity and specificity data are contradictory and differ depending on the study population. In our prospective study on pulmonary Af diseases in CF, we determined specific IgG m3 in order to test its suitability as a biomarker for acute Af diseases and as a follow-up parameter. In this prospective single center study, 109 patients with CF were screened from 2016 to 2019 for Af-associated diseases. According to diagnostic criteria, they were divided into four groups (control, bronchitis, ABPA, pneumonia). The groups were compared with respect to the level of Af-specific IgG (ImmunoCAP Gm3). We performed a receiver operating characteristic (ROC) curve analysis to determine cut-off, sensitivity and specificity. Twenty-one patients could be enrolled for a follow-up examination. Of the 109 patients, 36 were classified as acute Af-disease (Af bronchitis, ABPA, Af pneumonia). Of these, 21 patients completed follow up-screening. The median Af-specific Gm3 was higher in the acute Af-disease groups. There was a significant difference in Af-specific IgG m3 compared to the control group without acute Af-disease. Overall, there was a large interindividual distribution of Gm3. A cut-off value of 78.05 mg/L for Gm3 was calculated to discriminate controls and patients with ABPA/pneumonia with a specificity of 75% and a sensitivity of 74.6%. The follow up examination of 21 patients showed a decrease of Gm3 in most patients without statistical significance due to the small number of follow up patients. Af specific IgG may be a useful biomarker for acute ABPA and Af pneumonia, but not for Af bronchitis in CF. However, due to the large interindividual variability of Gm3, it should only be interpreted alongside other biomarkers. Therefore, due to its broad availability, it could be suitable as a biomarker for ABPA and Af pneumonia in CF, if the results can be supported by a larger multicenter cohort.


Early Performance on an Eye Surgery Simulator Predicts Subsequent Resident Surgical Performance.
To examine early performance on an eye surgery simulator and its relationship to subsequent live surgical performance in a single large residency program. Retrospective study. Massachusetts Eye and Ear, Harvard Medical School, Department of Ophthalmology. In a retrospective study, we compared performance of 30 first-year ophthalmology residents on an eye surgery simulator to their surgical skills as third-year residents. Variables collected from the eye surgery simulator included scores on the following modules of the simulator (Eyesi, VRmagic, Mannheim, Germany): antitremor training level 1, bimanual training level 1, capsulorhexis level 1 (configured), forceps training level 1, and navigation training level 1. Subsequent surgical performance was assessed using the total number of phacoemulsification cataract surgery cases for each resident, as well as the number performed as surgeon during residency and scores on global rating assessment of skills in intraocular surgery (GRASIS) scales during the third year of residency. Spearman correlation coefficients were calculated between each of the simulator performance and subsequent surgical performance variables. We also compared variables in a small group of residents who needed extra help in learning cataract surgery to the other residents in the study. Relationships between Eyesi scores early in residency and surgical performance measures in the final year of residency. A total of 30 residents had Eyesi data from their first year of residency and had already graduated so that all subsequent surgical performance data were available. There was a significant correlation between capsulorhexis task score on the simulator and total surgeries (r = 0.745, p = 0.008). There was a significant correlation between antitremor training level 1 (r = 0.554, p = 0.040), and forceps training level 1 (r = 0.622, p = 0.023) with primary surgery numbers. There was a significant correlation between forceps training level 1 (r = 0.811, p = 0.002), and navigation training level 1 (r = 0.692, p = 0.013) with total GRASIS score. There was a significant inverse correlation between total GRASIS score and residents in need of extra help (r = -0.358, p = 0.003). Module scores on an eye surgery simulator early in residency may predict a resident׳s future performance in the operating room. These scores may allow early identification of residents in need of supplemental training in cataract surgery.


Receptor autoradiographical evidence of a preferential reduction of binding sites for atrial natriuretic factor in renal papilla of the spontaneously hypertensive rat.
In the spontaneously hypertensive rat (SHR) as well as in the pathophysiological states with volume retention, high levels of atrial natriuretic factor (ANF) do not produce adequate diuresis and natriuresis. We have investigated the question whether the reduced effectiveness of ANF could be due to a reduction of the ANF binding. Evidence is provided by quantitative autoradiography with [125I]ANF than higher ANF plasma levels in SHRSP compared to normotensive WKY rats are associated with a reduced number of binding sites (25%) in the renal papilla as well as in the subfornical organ (69%). This could contribute to the reduced response of ANF in SHRSP.


[Hyperhomocysteinemia in pediatric age and nutritional aspects of folates: an early cardiovascular risk factor].
During the last decade, scientific evidence is mounting that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Despite this evidence, however, there are still concerns about the mechanisms(s) by which homocysteine exerts its pro-atherogenic effect, and it is unclear whether the decreased plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk. Experimental studies have shown that many possible mechanisms are implicated in the pro-atherogenic effect of homocysteine. Endothelial function is altered in subjects with hyperhomocysteinemia, and endothelial dysfunction is correlated with plasma levels of homocysteine. Exercise training reduces plasma levels of homocysteine and improves endothelial function, however without evidence of a better outcome. Larger studies are needed in order to demonstrate that the reduction of plasma levels of homocysteine by oral supplementation with folates and vitamins B6 and B12 translates into a decreased incidence of ischemic events, in particular in patients with documented coronary artery disease and ischemic encephalopathy.


Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma.
Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation. Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated (sporadic group). A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median of 34.5 months without morbidity. Median tumor doubling time was 17 months. Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and less functional than sporadic pheochromocytomas.


Significant postictal hypotension: expanding the spectrum of seizure-induced autonomic dysregulation.
Periictal autonomic dysregulation is best studied using a "polygraphic" approach: electroencephalography ([EEG]), 3-channel electrocardiography [ECG], pulse oximetry, respiration, and continuous noninvasive blood pressure [BP]), which may help elucidate agonal pathophysiologic mechanisms leading to sudden unexpected death in epilepsy (SUDEP). A number of autonomic phenomena have been described in generalized tonic-clonic seizures (GTCS), the most common seizure type associated with SUDEP, including decreased heart rate variability, cardiac arrhythmias, and changes in skin conductance. Postictal generalized EEG suppression (PGES) has been identified as a potential risk marker of SUDEP, and PGES has been found to correlate with post-GTCS autonomic dysregulation in some patients. Herein, we describe a patient with a GTCS in whom polygraphic measurements were obtained, including continuous noninvasive blood pressure recordings. Significant postictal hypotension lasting >60 s was found, which closely correlated with PGES duration. Similar EEG changes are well described in hypotensive patients with vasovagal syncope and a similar vasodepressor phenomenon, and consequent cerebral hypoperfusion may account for the PGES observed in some patients after a GTCS. This further raises the possibility that profound, prolonged, and irrecoverable hypotension may comprise one potential SUDEP mechanism.


Dosimetric analysis of the use of CBCT in diagnostic radiology: sinus and middle ear.
The use of cone beam computed tomography (CBCT) in diagnostic radiology departments is increasing. Several discussions arise whether with the CBCT application, some multi-slice CT (MSCT) examinations can be replaced by it. High hopes are set regarding the dosimetric aspects of CBCT: are patient doses in between those of conventional X-rays and MSCT? In this study, effective dose and organ doses were evaluated for two non-dental CBCT examinations: sinus and middle ear. A comparison with the dose obtained with a MSCT protocol was performed. Moreover, the sinus examination was also compared with the dose obtained by projection radiography (RX). Effective doses were estimated from thermoluminescent detector dose measurements in an anthropomorphic phantom and were compared against Monte Carlo simulations. Results show that the effective dose for the sinus examination is more than three times higher with MSCT than with CBCT and about five times lower with RX compared with CBCT, whereas for the middle ear examination, the effective dose obtained with MSCT is almost six times higher than that of CBCT. Finally, a sensitivity study on the size and position of the CBCT field of view showed the influence of these two factors on the dose received by the patient.


Effects of different doses of caffeine on anaerobic exercise in boys.
This study investigated effects of low (1 mg·kg-1), moderate (3 mg·kg-1) and high (5 mg·kg-1) doses of caffeine on anaerobic performance in boys. Twenty-six 8- to 10-year-old boys participated in a double-blind, crossover, counter-balanced study. Boys received in random order a placebo (PL) or anhydrous caffeine: 1 (CAF-1), 3 (CAF-3), or 5 (CAF-5) mg caffeine·kg-1 body mass in cherry flavored Sprite. Sixty minutes following consumption boys performed a static handgrip test and then a 30-s Wingate test. Maximal grip strength (21.5 ± 4.9 & 21.6 ± 4.7 vs. 20.4 ± 4.0 kg) was significantly higher in CAF-5 & CAF-3 vs PL, respectively. Absolute and relative peak power (287 ± 72 vs 281 ± 69 W & 8.0 ± 0.9 vs 7.8 ± 1.0 W·kg-1) were significantly higher in CAF-3 vs PL, respectively. Mean power (153 ± 48 vs 146 ± 43 W) was significantly higher in CAF-5 vs PL, respectively. Peak Wingate HR was significantly higher (189 ± 8 vs 185 ± 9 beats·min-1) in CAF-5 vs PL, respectively. These findings suggest that in boys CAF-1 did not affect performance. During the Wingate test CAF-3 resulted in higher peak power while CAF-5 increased mean power. The significant increase in peak HR following the Wingate test is likely related to greater mean power generated during CAF-5.


Renal catecholamines and alpha 2-adrenergic receptors in salt-related and genetic hypertension.
Increased dietary salt intake alters renal function which often leads to deleterious cardiovascular consequences. Studies were carried out to characterize the effects of high-salt diets on renal catecholamines and alpha 2-adrenergic receptors. These parameters were evaluated in both genetic and acquired forms of hypertension and also in normotensive rats on high-salt diets. Renal catecholamine content was determined by high-performance liquid chromatography with electrochemical detection. Renal alpha 2-adrenergic receptor-binding studies were performed on whole kidney homogenates using 3H-p-aminoclonidine to label both high- (0.5 nM) and low-affinity (5.0 nM) renal alpha 2-adrenergic receptors. Increased salt intake elevated blood pressure, decreased renal norepinephrine stores and resulted in renal alpha 2-adrenergic receptor up-regulation in deoxycorticosterone acetate salt hypertensive rats, Dahl-S rats and COX-SHR. The decreased renal stores of norepinephrine (NE) appeared to reflect increased renal NE utilization. In contrast, SHR (Charles River) had elevated NE stores and alpha 2-adrenergic receptors while on normal salt diets. Short-term (10-14 days) exposure to high-salt diets had modest effects in normotensive rats or COX-SHR, although it was sufficient to increase low affinity renal alpha 2-adrenergic receptor number. Renal dopamine metabolism was also altered by high-salt diets. These studies demonstrated a relationship between renal NE content and renal alpha 2-adrenergic receptors. The implications of this relationship and other salt-related changes in renal catecholamine metabolism were discussed as they pertained to hypertension and renal function.


Adrenocorticotropic hormone may be transported directly from the pituitary to the brain.
Experiments were designed to test the hypothesis that pituitary hormones may be delivered directly to the brain. Concentrations of adrenocorticotropic hormone (ACTH) in the plasma were determined in blood samles obtained simultaneously from the carotid artery, the sagittal sinus, and the jugular vein of three awake sheep. Seizures were induced electrically to stimulate ACTH secretion, and at precise intervals thereafter several simultaneous comparisons were made in each animal. In many of the post-seizure comparisons, the ACTH plasma concentrations within the sagital sinus exceeded those within the carotid artery as well as those within the jugular vein, indicating that this hormone was released from the pituitary and carried directly through capillary beds of brain to the venous blood within the sagittal sinus. The experiment was repeated in one hypophysectomized sheep and, in this animal, ACTH concentration in the plasma was reduced, but that in the sagittal sinus still was elevated after the seizure, an indication that some ACTH (or ACTH-like material) was released from the brain itself.


Expression and clinical significance of connective tissue growth factor (CTGF) in Graves' ophthalmopathy.
To examine the expression of connective tissue growth factor (CTGF) in human cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO) and investigate whether a correlation exists between the presence of CTGF protein and clinical parameters of the disease. The protein expression levels of CTGF were analysed by western blots in cultured orbital fibroblasts from 10 patients with GO and 7 age-matched normal controls. Associations between the protein expression of CTGF and the clinical factors of GO, including clinical demographics, thyroid function, clinical activity score (CAS) and ophthalmopathy index (OI), was evaluated. The mean protein expression levels of CTGF in the GO orbital fibroblasts were significantly higher than those of normal controls (p<0.001). Based on further analysis, the protein expression levels of CTGF in the GO orbital fibroblasts had significant correlation with gender (p=0.029), serum levels of thyrotropin receptor antibodies (p=0.029), CAS (p=0.048) and OI (p=0.043). Especially, there was a significant correlation between protein expression levels of CTGF and lid oedema (p=0.037), proptosis (p=0.045) and corneal involvement (p=0.001). Our findings revealed that the protein expression levels of CTGF in the GO orbital fibroblasts were significantly highly expressed than those of normal controls, and the elevated CTGF was associated with clinical characteristics and evolution, indicating CTGF may play a role in the pathogenesis and pathophysiology of GO.


Wavelets, ridgelets, and curvelets for Poisson noise removal.
In order to denoise Poisson count data, we introduce a variance stabilizing transform (VST) applied on a filtered discrete Poisson process, yielding a near Gaussian process with asymptotic constant variance. This new transform, which can be deemed as an extension of the Anscombe transform to filtered data, is simple, fast, and efficient in (very) low-count situations. We combine this VST with the filter banks of wavelets, ridgelets and curvelets, leading to multiscale VSTs (MS-VSTs) and nonlinear decomposition schemes. By doing so, the noise-contaminated coefficients of these MS-VST-modified transforms are asymptotically normally distributed with known variances. A classical hypothesis-testing framework is adopted to detect the significant coefficients, and a sparsity-driven iterative scheme reconstructs properly the final estimate. A range of examples show the power of this MS-VST approach for recovering important structures of various morphologies in (very) low-count images. These results also demonstrate that the MS-VST approach is competitive relative to many existing denoising methods.


Assessing the cost-effectiveness of annual COVID-19 booster vaccination in South Korea using a transmission dynamic model.
We evaluated the cost-effectiveness of South Korea's planned annual coronavirus disease 2019 (COVID-19) booster campaign scheduled for October 2023. An age-structured mathematical model was used to analyze the public impacts and cost-effectiveness of vaccination across three vaccination strategies: uniform allocation and prioritizing those over 65 or those over 50 years old. We calculated the incremental cost per quality-adjusted life year (QALY) from both healthcare and societal perspectives. The maximum vaccine cost for cost-effectiveness was also identified. Our analysis highlights the cost-effectiveness of South Korea's annual COVID-19 vaccination program in mitigating health and economic impacts. The most cost-effective strategy is uniform vaccine allocation, offering the lowest incremental cost-effectiveness ratio (ICER) at US$ 25,787/QALY. However, with a relatively high attack rate, the strategy prioritizing individuals over 65 years emerges as more cost-effective, lowering the ICER to US$ 13,785/QALY. Prioritizing those over 50 was less cost-effective. All strategies were cost-saving from a societal perspective, with cost-effectiveness being more sensitive to vaccine price than to its effectiveness. Our results imply a potential strategy shift in current vaccination plan, with uniform vaccine distribution being more cost-effective than prioritizing older adults. Early estimation of viral transmissibility and vaccine effectiveness is crucial in determining the most cost-effective vaccine allocation approach.


Involvement of the Nrf2/HO-1/CO axis and therapeutic intervention with the CO-releasing molecule CORM-A1, in a murine model of autoimmune hepatitis.
Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2, and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM-A1 determines an improvement in several sero-immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM-A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans.


Physical and Anthropometric Characteristics Do Not Differ According to Birth Year Quartile in High-Level Junior Australian Football Players.
The aim of this study was to explore differences in the physical fitness and anthropometric profiles between birth year quartiles of players attending the Australian Football League (AFL) National Draft Combine. Date of birth, anthropometric, 20 m sprint, vertical and running vertical jump, AFL planned agility, and 20 m Multi-Stage Fitness Test (MSFT) data were obtained for players selected to attend the Combine between 1999 and 2019 (n = 1549; Mage = 18.1; SDage = 0.3). The underlying density distributions of the data were visually explored using violin plots overlaid with box and whisker plots. A multivariate analysis of variance (MANOVA) was then used to model the main effect of birth quartile (four levels) on the physical and anthropometric scores. Results showed that physical and anthropometric test scores did not significantly differ according to birth quartile (V = 0.008, F = 0.880, p = 0.631). We conclude that the physical and anthropometric profiles of high-level junior Australian Football players were similar according to birth year quartile across the modeled period. Therefore, how players utilize their physical and anthropometric attributes during game-play via contextualized, representative assessments, such as small-sided games, should be considered when examining potential causes of a RAE.


Convergence in feeding posture occurs through different genetic loci in independently evolved cave populations of Astyanax mexicanus.
When an organism colonizes a new environment, it needs to adapt both morphologically and behaviorally to survive and thrive. Although recent progress has been made in understanding the genetic architecture underlying morphological evolution, behavioral evolution is poorly understood. Here, we use the Mexican cavefish, Astyanax mexicanus, to study the genetic basis for convergent evolution of feeding posture. When river-dwelling surface fish became entrapped in the caves, they were confronted with dramatic changes in the availability and type of food source and in their ability to perceive it. In this setting, multiple independent populations of cavefish exhibit an altered feeding posture compared with their ancestral surface forms. We determined that this behavioral change in feeding posture is not due to changes in cranial facial morphology, body depth, or to take advantage of the expansion in the number of taste buds. Quantitative genetic analysis demonstrates that two different cave populations have evolved similar feeding postures through a small number of genetic changes, some of which appear to be distinct. This work indicates that independently evolved populations of cavefish can evolve the same behavioral traits to adapt to similar environmental challenges by modifying different sets of genes.


The effects of pressure-induced right ventricular hypertrophy on left ventricular diastolic properties and dynamic geometry in the conscious dog.
To determine whether chronic pressure overload and hypertrophy of the right ventricle alter the diastolic properties of the left ventricle, six adult dogs underwent banding of the pulmonary artery and were instrumented for studies 8 months later. Fourteen control dogs were also studied. Pressure and dimension data were collected from the dogs while they were awake and unsedated. The anterior-posterior, septal-free wall, and base-apex axis diameters of the left ventricle were measured with ultrasonic dimension transducers. Right and left ventricular pressures were measured with micromanometers. Pulmonary arterial banding resulted in increased right ventricular/body mass ratios (2.70 +/- 0.36 g/kg vs 1.52 +/- 0.15 g/kg control; p less than or equal to .05) and increased left ventricular/body mass ratios (4.84 +/- 0.64 g/kg vs 4.21 +/- 0.49 g/kg control; p less than or equal to .05). Right ventricular peak systolic and end-diastolic pressures were higher among the banded dogs (50 +/- 20/7 +/- 5 mm Hg vs 31 +/- 6/3 +/- 2 mm Hg control; p less than or equal to .05). A rearrangement in the three-dimensional geometry of diastolic filling occurred in the banded dogs. Extension from unstressed diastolic dimension (strain) in the base-apex axis was significantly larger in the banded dogs at left ventricular transmural pressures of 12, 8, and 4 mm Hg; strains in the septal-free wall axis were significantly smaller at transmural pressures of 12 and 8 mm Hg. Normalized diastolic left ventricular pressure-volume data and midwall circumferential stress-strain data were fit to the Kelvin viscoelastic equation. The normalized pressure-volume relationships of the banded dogs lay significantly to the left of those of the controls, indicating a loss of left ventricular chamber compliance. The midwall circumferential stress-strain relationships of the banded dogs were also shifted to the left, indicating a loss of intrinsic myocardial compliance. Thus, during the course of right ventricular hypertrophy caused by right ventricular pressure overload, alterations in the mass, geometry, and material properties of the left ventricle occur. At 8 months the chamber compliance of the left ventricle is compromised by these changes.


Surface micro/nanotopography, wetting properties and the potential for biomimetic icephobicity of skunk cabbage Symplocarpus foetidus.
Lotus (Nelumbo nucifera) is known for its two remarkable properties: superhydrophobicity and thermogenesis; however, the relationship between these two properties remains obscure. Most botanists agree that thermogenesis helps to attract pollinators, while non-wetting helps to catch pollinators and prevents contamination. Here we investigate the surface micro- and nanotopography and wetting properties of eastern skunk cabbage (Symplocarpus foetidus), another thermogenic plant, which is known for its ability to melt snow. The skunk cabbage leaves are hydrophobic but not superhydrophobic, and they have high contact angle hysteresis (similar to the rose petal effect). We develop a heat transfer model to relate icephobicity with heat transfer and discuss the biomimetic potential that both thermogenic and superhydrophobic plants may have for icephobicity in soft materials.


A replication study of genetic risk loci for ischemic stroke in a Dutch population: a case-control study.
We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS.


Best Nursing Intervention Practices to Prevent Non-Communicable Disease: A Systematic Review.
Objectives: To explore nursing health education interventions for non-communicable disease patients. Methods: The design was a systematic review of research work published between 2008 and 2018. The data sources included the Web of Science, PubMed, Scopus, COCHRANE, and LILACS. The studies that met the inclusion were assessed, and the analysis for methodological quality through the recommended tools CASPe, and JADAD. Results: Fifteen original studies from eight counties were included in the review; Findings revealed 13 studies with randomized samples and six used power analysis. Nurses' interventions included house calls, home care, and individual and group health education. Conclusion: Nursing interventions showed 76.4% the effectiveness of results in patient outcomes to promote and improve healthier lifestyles and quality of life of non-communicable disease patients. This review discloses the significant impact of nursing health education interventions. Nursing leadership and political decision-makers should consider providing programs to enhance health education knowledge and abilities. All of this can favor the sustainability of the global economy by changing the life style of thousands of people worldwide. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020208809.


[Effect of Soviet-made prostaglandin E1 on the aggregation of thrombocytes and erythrocytes].
The effect of prostaglandin E1 in a concentration of 0.1 gamma/ml on the aggregation and disaggregation of thrombocytes and erythrocytes in vitro was studied. Prostaglandin E1 was found to materially reduce the aggregation and to produce disaggregation of thrombocytes. A somewhat diminished aggregation of erythrocytes was also noted. Prostaglandin E1 failed to cause disaggregation of erythrocytes.


bioWeb3D: an online webGL 3D data visualisation tool.
Data visualization is critical for interpreting biological data. However, in practice it can prove to be a bottleneck for non trained researchers; this is especially true for three dimensional (3D) data representation. Whilst existing software can provide all necessary functionalities to represent and manipulate biological 3D datasets, very few are easily accessible (browser based), cross platform and accessible to non-expert users. An online HTML5/WebGL based 3D visualisation tool has been developed to allow biologists to quickly and easily view interactive and customizable three dimensional representations of their data along with multiple layers of information. Using the WebGL library Three.js written in Javascript, bioWeb3D allows the simultaneous visualisation of multiple large datasets inputted via a simple JSON, XML or CSV file, which can be read and analysed locally thanks to HTML5 capabilities. Using basic 3D representation techniques in a technologically innovative context, we provide a program that is not intended to compete with professional 3D representation software, but that instead enables a quick and intuitive representation of reasonably large 3D datasets.


Interactions of organic compounds with wastewater dissolved organic matter: role of hydrophobic fractions.
The role of structural fractions of dissolved organic matter (DOM) from wastewater in the sorption process of hydrophobic organic compounds is still not clear. In this study, DOM from two wastewater treatment plants (Lachish and Netanya, Israel) was fractionated to hydrophobic acid (HoA) and hydrophobic neutral (HoN) fractions. The fractions were characterized and their sorptive capabilities for s-triazine herbicides and polycyclic aromatic hydrocarbons (PAHs) were studied. For all sorbates, the binding to the HoN fractions was much higher than to HoA fractions. The HoA fractions were more polar than the HoN fractions, containing a higher level of carboxylic functionalities. However the higher binding coefficients of atrazine (2-chloro-4-ethylamine-6-isopropylamino-s-triazine) and ametryn [2-(ethylamino)-4-isopropylamino-6-methyl-thio-s-triazine] obtained for the HoN fractions suggest that their sorption is governed by hydrophobic-like interactions rather than H bonding. The values of binding coefficients of PAHs measured for the HoN fractions were within the range reported for humic acids and much higher than other fractions, suggesting that this fraction plays an important role in the overall sorption of these compounds by DOM. Higher sorption coefficients were measured for the Netanya DOM sample containing higher level of hydrophobic fractions (HoA + HoN) than the Lachish DOM, suggesting that the sorption of hydrophobic organic compounds by DOM is governed by the level of these structural substances. The evaluation of mobility of organic pollutants by wastewater irrigation requires not only assessment of the total carbon concentration but also, more importantly, the content of the hydrophobic fractions.


Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus.
A gene encoding a polypeptide with homology to mammalian vascular endothelial growth factors (VEGFs) has been discovered in the genome of orf virus (OV), a parapoxvirus that affects sheep and goats and, occasionally, humans. The gene is transcribed abundantly early in infection and is found immediately outside the inverted terminal repeat at the right end of the genome. In the NZ2 strain of OV (OV NZ2), the gene encodes a polypeptide with a molecular size of 14.7 kDa, while in another strain, OV NZ7, there is a variant gene that encodes a polypeptide of 16 kDa. The OV NZ2 and OV NZ7 polypeptides show 22 to 27% and 16 to 23% identity, respectively, to the mammalian VEGFs. The viral polypeptides are only 41.1% identical to each other, and there is little homology between the two genes at the nucleotide level. Another unusual feature of these genes is their G+C content, particularly that of OV NZ7. In a genome that is otherwise 63% G+C, the OV NZ2 gene is 57.2% G+C and the OV NZ7 gene is 39.7% G+C. The OV NZ2 gene, but not the OV NZ7 gene, is homologous to the mammalian VEGF genes at the DNA level, suggesting that the gene has been acquired from a mammalian host and is undergoing genetic drift. The lesions induced in sheep and humans after infection with OV show extensive dermal vascular endothelial proliferation and dilatation, and it is likely that this is a direct effect of the expression of the VEGF-like gene.


A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia.
This trial tested the safety and efficacy of a regimen consisting of hydroxyurea followed by azacitidine, 75 mg/m(2) for 7 days, and gemtuzumab ozogamicin, 3 mg/m(2) on day 8, in older patients with newly diagnosed acute myeloid leukemia. Those achieving a complete remission received 1 consolidation treatment followed by 4 cycles of azacitidine. The patients were stratified into good-risk (age 60-69 years or performance status 0-1) and poor-risk (age ≥70 years and performance status 2 or 3) groups. Specific efficacy and safety goals were defined as being supportive of further study of the regimen. Eighty-three patients were registered in the good-risk cohort and 59 in poor-risk cohort, with median age of 71 and 75 years, respectively. In the good-risk group, 35 patients (44%) achieved a complete remission. Median relapse-free and overall survivals were 8 and 11 months, respectively. Six patients (8%) died within 30 days of registration. In the poor-risk group, 19 (35%) achieved a complete remission. Median relapse-free and overall survivals were 7 and 11 months, respectively. Seven patients (14%) died early. The results of this trial met predefined goals for efficacy and safety for the poor-risk cohort but not the good-risk group. .


Immunohistochemical expression of MGMT in gliomas and its role in ascertaining patient survival.
MGMT (O-6-methylguanine-DNA methyl transferase) is a DNA repair enzyme with implications on chemoresistance and subsequent patient prognosis. This study investigated the association of MGMT with the various grades and subtypes of gliomas and evaluated the associated clinical outcome of these patients. This observational longitudinal follow up study spun over a period of 36 months and included 33 patients with primary glioma who underwent surgical interventions and chemoradiotherapy at a tertiary care center in Kolkata. The surgical samples were processed and histopathologically typed. Immunohistochemical analysis was done using anti-MGMT antibody and MGMT status was determined. Patients were followed up for 3 years. Males were 1.3 times more commonly affected by gliomas. Mean age was 42.9 years for females and 47.2 years for males. Frontal lobe was the most commonly involved site whereas focal neurological deficit was the most common symptom. Karnofsky performance score was higher for low grade gliomas and lower for high grade gliomas (p=0.04). Significant association was found between histopathological grade and MGMT immunoexpression (p=0.0001) as well as histopathological subtype and MGMT status (p=0.0036). On follow up, mean survival of the patients was 25.4 months. Significant association was found between MGMT status and survival of the patients (p=0.0437). MGMT immunoexpression is significantly associated with different grades and subtypes of gliomas. In addition, MGMT has significant implications on chemoresistance and patient survival. Hence, MGMT expression should be mandatorily checked before starting the chemotherapy.


Endothelium-mediated hepatocyte recruitment in the establishment of liver-like tissue in vitro.
A major goal of liver tissue engineering is to understand how the constituent cell types interact to achieve liver-specific structure and function. Here we show that hepatocytes migrate toward and adhere to endothelial vascular structures formed on Matrigel in vitro, and that hepatocyte recruitment is dependent on endothelium-derived hepatocyte growth factor. The hepatocyte-decorated endothelial vascular structures resemble In vivo sinusoids containing plate-like structures, bile canaliculi, and a lumen. The sinusoid-like structures retained cytochrome P450 expression and activity, in addition to stable albumin expression and secretion rate for over 2 months in vitro. The stability of the sinusoid-like structures was dependent on the presence of vimentin-positive fibroblasts in culture. The sinusoid-like structures formed by hepatocytes and pure populations of endothelial cells collapsed after 10 days in culture. In contrast, culture of hepatocytes with fibroblast-contaminated human dermal microvascular endothelial cells or a combination of human umbilical vein endothelial cells and normal human dermal fibroblasts resulted in stable sinusoid-like structures surrounded by a fibroblastic capsule that maintained liver specific functions for several months in vitro. These results demonstrate that specification of endothelial cell position ultimately determines hepatocyte position in vitro, suggesting that similar interactions might occur In vivo. The novelty of the culture's sinusoid-like organization and long-term function suggest a new model for the study of liver toxicity, ischemia/reperfusion injury, and fibrosis.


Massive transfusion and nonsurgical hemostatic agents.
Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.


Resection of metastatic renal cell carcinoma.
Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.


Construction of hearing percentiles in women with non-constant variance from the linear mixed-effects model.
Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems. We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model. We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging. However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean. We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles. We present a number of approaches. First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency. Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates.


Intramuscular and surface electromyogram changes during muscle fatigue.
Twelve male subjects were tested to determine the effects of motor unit (MU) recruitment and firing frequency on the surface electromyogram (EMG) frequency power spectra during sustained maximal voluntary contraction (MVC) and 50% MVC of the biceps brachii muscle. Both the intramuscular MU spikes and surface EMG were recorded simultaneously and analyzed by means of a computer-aided intramuscular spike amplitude-frequency histogram and frequency power spectral analysis, respectively. Results indicated that both mean power frequency (MPF) and amplitude (rmsEMG) of the surface EMG fell significantly (P less than 0.001) together with a progressive reduction in MU spike amplitude and firing frequency during sustained MVC. During 50% MVC there was a significant decline in MPF (P less than 0.001), but this decline was accompanied by a significant increase in rmsEMG (P less than 0.001) and a progressive MU recruitment as evidenced by an increased number of MUs with relatively large spike amplitude. Our data suggest that the surface EMG amplitude could better represent the underlying MU activity during muscle fatigue and the frequency powers spectral shift may or may not reflect changes in MU recruitment and rate-coding patterns.


Current In Vitro Methods to Determine Hepatic Kpuu: A Comparison of Their Usefulness and Limitations.
Unbound intrahepatic drug concentrations determine the interaction potential with intracellular targets related to toxicity, pharmacokinetics, or pharmacodynamics. Recently, the unbound liver-to-blood partition coefficient (Kpuu) based on the Extended Clearance Model (ECM) has been developed providing indirect estimates of unbound intrahepatic drug concentrations. This study aimed to determine Kpuu for 18 diverse drug compounds by 3 alternative in vitro methods and to compare the outcome with the ECM approach. Kpuu was calculated from independent measurements of hepatocellular drug accumulation (Kp) and unbound fraction in hepatocytes (fuhep) either assessed from steady-state accumulation at 4°C (temperature method), using equilibrium dialysis (homogenization method), or empirically from logD7.4 (logD7.4 method). Deviations to ECM-based Kpuu data were closely linked to the absence of intrinsic clearance processes (metabolism, biliary secretion) in the investigated methods. Differences in fuhep additionally contributed to deviations in Kpuu. The homogenization method generally provided lowest fuhep values, especially for compounds with high molecular weight or low logD7.4. Kpuu values of compounds with low intrinsic clearance correlated well between the ECM and temperature methods independent of physicochemical properties. Therefore, only the ECM provides an integrated quantitative determination of hepatic Kpuu. Temperature and homogenization methods, however, represent useful alternatives if compound properties are appropriately considered.


[Degenerate oligonucleotide primed-PCR technology establishment and its sensitivity test analysis].
To establish a whole genome amplification testing system based on degenerate oligonucleotide primed-PCR (DOP-PCR) and to explore its reliability and sensitivity. DOP-PCR amplified production was detected by fluorescent labeled multiplex STR amplification and capillary electrophoresis detection system to determine reliability and sensitivity of DOP-PCR system. DOP-PCR system was successfully established and the detection sensitivity reached 5 cells (30 pg) by pretreatment of DOP-PCR and then detection of STR genotyping. The system established in this study is reliable and more testing sensitive for forensic trace evidence.


Genotyping by Sequencing of Cultivated Lentil (Lens culinaris Medik.) Highlights Population Structure in the Mediterranean Gene Pool Associated With Geographic Patterns and Phenotypic Variables.
Cultivated lentil (Lens culinaris Medik.) is one of the oldest domesticated crops and one of the most important grain legumes worldwide. The Mediterranean Basin holds large part of lentil biodiversity; however, no genetic structure was defined within the Mediterranean gene pool. In this study, we used high-throughput genotyping by sequencing to resolve the genetic structure of the Mediterranean ex situ lentil collection held at the Italian National Research Council. Sequencing of a 188-plex genotyping-by-sequencing library and bioinformatics treatment of data yielded 6,693 single nucleotide polymorphisms. Analysis of nonredundant genotypes with nonparametric and parametric methods highlighted the occurrence of five highly differentiated genetic clusters. Clustering could be related to geographic patterns and phenotypic traits, indicating that post-domestication routes introducing cultivation in Mediterranean countries and selection were major forces shaping lentil population structure. The estimation of the fixation index FST at individual single nucleotide polymorphism loci allowed the identification of distinctive alleles across clusters, suggesting the possibility to set up molecular keys for the assignment of lentil germplasm to specific genetic groups. Finally, significant associations between markers and phenotypic data were identified. Overall, the results of this study are of major importance for lentil conservation genetics and breeding and provide insights on the lentil evolutionary history.


Phosphatidylinositol biosynthesis in Saccharomyces cerevisiae: purification and properties of microsome-associated phosphatidylinositol synthase.
The membrane-associated phospholipid biosynthetic enzyme phosphatidylinositol synthase (cytidine 5'-diphospho-1,2-diacyl-sn-glycerol:myo-inositol 3-phosphatidyltransferase, EC 126.96.36.199) was purified 1,000-fold from the microsomal fraction of Saccharomyces cerevisiae. The purification procedure included Triton X-100 solubilization of the microsomal membranes, CDPdiacylglycerol-Sepharose (Larson et al., Biochemistry 15:974-979, 1976) affinity chromatography, and chromatofocusing. The procedure resulted in the isolation of a nearly homogeneous protein preparation with an apparent minimum subunit molecular weight of 34,000, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Phosphatidylinositol synthase was dependent on manganese and Triton X-100 for maximum activity. The pH optimum was 8.0. Thioreactive agents inhibited enzyme activity. The energy of activation was found to be 35 kcal/mol (146,540 J/mol). The enzyme was reasonably stable at temperatures of up to 60 degrees C.


Flow of condensed particles around a packing front visualized by drying colloidal suspensions on a tilted substrate.
A gravity effect was demonstrated for 10 nm particles drying in colloidal suspensions. The particles were well-dispersed and did not sediment. However, when a suspension was dried on a tilted directional cell, a clear downward flow of particles was observed around the packing front, which was the boundary between the packed particles layer and the suspension. Three particle sizes (10-110 nm) were examined, with the most pronounced effect being on the 10 nm particles. The primary origin of the downflow was attributed to condensation of particles near the packing front and the subsequent increase in the overall density of the condensed layer. Because of the flow, the packing front was not parallel to the drying interface and tilted cracks formed in the packed layer. A mathematical model was proposed that considered conservation of the suspended particles in the condensed layer. Three competing factors of particle transport (advection, particle consumption by packing, and particle transport by the downward flow) were used to explain the experimental results. Overall, the results suggested that simple substrate tilting would be useful to evaluate whether suspended particles are easily packed or not during drying.


Vitamin D deficiency and supplementation and relation to cardiovascular health.
Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.


Surveillance testing in patients with early stage breast cancer: a review.
The optimal breast cancer surveillance testing program for early-stage breast cancer patients has not yet been defined. The results of three surveys evaluating patterns of follow-up have indicated that most physicians practice some level of routine surveillance testing (history, physical examination, and yearly mammogram), but there is extreme variation in follow-up practices from physician to physician, especially in the use of blood tests, bone scan, and chest X-ray. The results of numerous retrospective studies and two large randomized prospective studies have indicated that: 1) most recurrences are detected by the history and physical exam; and 2) intensive surveillance testing of asymptomatic patients does not improve overall survival. Several studies on the psychosocial impact of follow-up testing have indicated that: 1) patients desire frequent follow-up visits; 2) patients undervalue the clinical exam and overestimate the value of laboratory and X-ray studies in detecting recurrences.


Hastening orientation sensitivity.
Previous perceptual learning studies have shown that sensitivity to subtle orientation differences improves with practice at oblique axes but not with practice at cardinal axes. The cause of this anisotropy in angular resolution is uncertain, and it is not known whether the same anisotropy pertains to temporal resolution-the minimum stimulus duration needed to achieve a specified angular resolution. Here, we investigated the hypothesis that cardinal improvements were previously absent because long stimulus durations yielded maximal precision, even at the start of training. Accordingly, we exploited the relatively imprecise responses that occur naturally when masked stimuli are presented for extremely brief durations. After 110,000 trials were completed over seven daily sessions, temporal resolution improved by 51% at cardinal axes and by 86% at oblique axes. This hastening of the visual response was accompanied by significant improvements in angular resolution, which were specific to the trained axis. The data demonstrate plasticity in the response to cardinal orientations and indicate that sufficient initial levels of neural imprecision may be necessary for perceptual learning.


Effect of Training on Administration of Electroconvulsive Therapy by Junior Doctors.
An instrument was designed to rate the administration of electroconvulsive therapy. The performance of junior doctors was rated before and after videotape training in technique. The group showed a marked increase in ratings following training. The limitations and importance of the study are discussed.


Demonstrating sub-nm closed loop MEMS flattening.
Ground based high-contrast imaging (e.g. extrasolar giant planet detection) has demanding wavefront control requirements two orders of magnitude more precise than standard adaptive optics systems. We demonstrate that these requirements can be achieved with a 1024-Micro-Electrical-Mechanical-Systems (MEMS) deformable mirror having an actuator spacing of 340 microm and a stroke of approximately 1 microm, over an active aperture 27 actuators across. We have flattened the mirror to a residual wavefront error of 0.54 nm rms within the range of controllable spatial frequencies. Individual contributors to final wavefront quality, such as voltage response and uniformity, have been identified and characterized.


Association between Chronotype, Physical Activity and Sedentary Behaviour: A Systematic Review.
The aim of this systematic review is to compile and assess the scientific evidence about the relationship between chronotypes and physical activity (PA). Methods: A systematic review was executed using a structured electronic search in PubMED, Cochrane Library, PsycInfo and Trip Database. The searches employed keywords such as chronotype, sleep, acrophase, chronotype preference, morningness, physical activity and sedentary, using MeSH terms. JBI critical tools were used to appraise methodological aspects. This systematic review includes 23 studies and a total of 505,375 participants. The results show that evening chronotypes are associated with less PA and more time in sedentary activities. It occurs independently of the instruments used to collect information about chronotype and PA. Nevertheless, this association could be mitigated in young populations and university stages. The chronotypes are clearly associated with the PA level and the sedentary behaviour, especially in the population over their mid-twenties. Evening chronotypes are associated with less PA and more time in sedentary activities compared to morning chronotypes.


Prognostic factors influencing survival after nephroureterectomy for transitional cell carcinoma of the upper urinary tract.
We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of disease-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p<0.0001), tumor grade (p=0.0324), and venous invasion (p<0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p=0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.


AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test.
The mechanism by which lithium exerts either its anti-manic or antidepressant effects remains to be fully elucidated. Although lithium inhibits the enzyme glycogen synthase kinase-3 (GSK-3) at concentrations that are relevant for treatment of bipolar disorder, it is unclear whether GSK-3-related mechanisms are responsible for its therapeutic effects in the treatment of this disease. We report that AR-A014418 (a selective GSK-3 inhibitor) induces behavioural changes that are consistent with the effects of antidepressant medications. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, a well-established model for antidepressant efficacy. In addition, the specificity of this effect is supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity. Taken together, these data support the hypothesis that lithium may exert its antidepressant effects through inhibition of GSK-3, and that novel small-molecule GSK-3 inhibitors may be useful for the treatment of bipolar disorder and depression.


Pelvis-Toe Distance: 3-Dimensional Gait Characteristics of Functional Limb Shortening in Hemiparetic Stroke.
We aimed to investigate whether a newly defined distance in the lower limb can capture the characteristics of hemiplegic gait compared to healthy controls. Three-dimensional gait analyses were performed on 42 patients with chronic stroke and 10 age-matched controls. Pelvis-toe distance (PTD) was calculated as the absolute distance between an anterior superior iliac spine marker and a toe marker during gait normalized by PTD in the bipedal stance. The shortening peak during the swing phase was then quantified as PTDmin. The sagittal clearance angle, the frontal compensatory angle, gait speed, and the observational gait scale were also collected. PTDmin in the stroke group showed less shortening on the affected side and excessive shortening on the non-affected side compared to controls. PTDmin on the affected side correlated negatively with the sagittal clearance peak angle and positively with the frontal compensatory peak angle in the stroke group. PTDmin in stroke patients showed moderate to high correlations with gait speed and observational gait scale. PTDmin adequately reflected gait quality without being affected by apparent improvements due to frontal compensatory patterns. Our results showed that various impairments and compensations were included in the inability to shorten PTD, which can provide new perspectives on gait rehabilitation in stroke patients.


Evidence for non-traditional activation of complement factor C3 during murine liver regeneration.
Complement signaling has been implicated as important for normal hepatic regeneration. However, the specific mechanism by which complement is activated during liver regeneration remains undefined. To address this question, we investigated the hepatic regenerative response to partial hepatectomy in wildtype mice, C3-, C4-, and factor B-null mice, and C4-null mice treated with a factor B neutralizing antibody (mAb 1379). The results showed that following partial hepatectomy, C3-null mice exhibit reduced hepatic regeneration compared to wildtype mice as assessed by quantification of hepatic cyclin D1 expression and hepatocellular DNA synthesis and mitosis. In contrast, C4-null mice and factor B-null mice demonstrated normal liver regeneration. Moreover, animals in which all of the traditional upstream C3 activation pathways were disrupted, i.e. C4-null mice treated with mAb 1379, exhibited normal C3 activation and hepatocellular proliferation following partial hepatectomy. In order to define candidate non-traditional mechanisms of C3 activation during liver regeneration, plasmin and thrombin were investigated for their abilities to activate C3 in mouse plasma in vitro. The results showed that both proteases are capable of initiating C3 activation, and that plasmin can do so independent of the classical and alternative pathways. These results show that C3 is required for a normal hepatic regenerative response, but that disruption of the classical- or lectin-dependent pathways (C4-dependent), the alternative pathway (factor B-dependent), or all of these pathways does not impair the hepatic regenerative response, and indicate that non-traditional mechanisms by which C3 is activated during hepatic regeneration must exist. In vitro analysis raises the possibility that plasmin may contribute to non-traditional complement activation during liver regeneration in vivo.