A newly developed peripheral anterior chamber depth analysis system: principle, accuracy, and reproducibility.
To develop a new, non-contact system for measuring anterior chamber depth (ACD) quantitatively, and to investigate its accuracy as well as interobserver and intraobserver reproducibility. The system scanned the ACD from the optical axis to the limbus in approximately 0.5 second and took 21 consecutive slit lamp images at 0.4 mm intervals. A computer installed program automatically evaluated the ACD, central corneal thickness (CT), and corneal radius of curvature (CRC) instantly. A dummy eye was used for investigating measurement accuracy. The effects of CT and CRC on the measurement results were examined using a computer simulation model to minimise measurement errors. Three examiners measured the ACD in 10 normal eyes, and interobserver and intraobserver reproducibility was analysed. The ACD values measured by this system were very similar to theoretical values. Increase of CRC and decrease in CT decreased ACD and vice versa. Data calibration using evaluated CT and CRC successfully reduced measurement errors. Intraobserver and interobserver variations were small. Their coefficient variation values were 7.4% (SD 2.3%) and 6.7% (0.7%), and these values tended to increase along the distance from the optical axis. The current system can measure ACD with high accuracy as well as high intraobserver and interobserver reproducibility. It has potential use in measuring ACD quantitatively and screening subjects with narrow angle.


Hot topic: effects of frequent milking in early lactation on milk yield and udder health.
A field study was conducted to evaluate the influence of milking frequency (3 or 6 times/d [3x or 6x, respectively]) during the initial 21 d of lactation on milk and milk component yield and mammary gland health as indicated by somatic cell count. During 2 seasons, spring and fall, multiparous cows were milked 6 times/d until d 21 of lactation and then returned to the 3 times/d frequency for the remainder of lactation (6x; n = 9). Multiparous cows milked 3 times/d from the beginning of lactation served as a control group (3x; n = 17). With the exception of milking frequency, all other aspects of management, including housing, milk harvesting, and feeding, were identical between the groups and were consistent with industry norms. Retrospective analysis of Dairy Herd Improvement Association records was used to evaluate milk yield, milk component yield, and somatic cell scores. As expected, 6x cows produced more milk on the first test day than 3x cows. Compared with 3x cows, higher milk yields persisted for 6x cows from test day 2 through 6, indicating a persistent effect of early lactation milking frequency on milk yield potential for that lactation. Milk component yield followed a similar pattern: 6x cows produced significantly more protein, fat, and total solids than did control cows throughout the study. With regard to udder health, 6x cows had lower somatic cell counts at the first test day relative to 3x cows and had reduced somatic cell scores for the first 3 mo of lactation, which suggests that early lactation milking frequency influences the mammary gland capacity to resist infection in addition to improving milk production efficiency.


Occupational asthma due to inhalation of chloramine-T. II. Demonstration of specific IgE antibodies.
In the sera of patients who developed asthmatic symptoms after exposure to chloramine-T, specific IgE antibodies are demonstrated by a polystyrene tube radioimmunoassay. These antibodies are directed against human serum albumin treated with chloramine-T. Specific antibodies of subclasses IgG1, IgG3 and IgG4 were not found. Histamine release in response to chloramine-T-treated human serum albumin was demonstrated using the peripheral blood leukocytes of one of the patients. To define the antigenic determinant to which the specific IgE antibodies are directed, radioimmunoassay and radioimmunoassay-inhibition studies were performed using several autologous and heterologous chloramine-T-treated proteins. Moreover, the inhibition capacities of chloramine-T and structurally related compounds were also determined. The results of these experiments indicate that the antigenic determinant is formed, at least in part, by the p-toluenesulfonyl group of the chloramine-T molecule.


Simultaneous analysis of multiple PCR amplicons enhances capillary SSCP discrimination of MHC alleles.
Major histocompatibility complex (MHC) genotyping still remains one of the most challenging issues for evolutionary ecologists. To date, none of the proposed methods have proven to be perfect, and all provide both important pros and cons. Although denaturing capillary electrophoresis has become a popular alternative, allele identification commonly relies upon conformational polymorphisms of two single-stranded DNA molecules at the most. Using the MHC class II (beta chain, exon 2) of the black kite (Aves: Accipitridae) as our model system, we show that the simultaneous analysis of overlapping PCR amplicons from the same target region substantially enhances allele discrimination. To cover this aim, we designed a multiplex PCR capable to generate four differentially sized and labeled amplicons from the same allele. Informative peaks to assist allele calling then fourfold those generated by the analysis of single PCR amplicons. Our approach proved successful to differentiate all the alleles (N=13) isolated from eight unrelated birds at a single optimal run temperature and electrophoretic conditions. In particular, we emphasize that this approach may constitute a straightforward and cost-effective alternative for the genotyping of single or duplicated MHC genes displaying low to moderate sets of divergent alleles.


Impact of a Layered Learning Practice Model on Delivery of Clinical Pharmacy Key Performance Indicators under a Tertiary Care Centre Oncology Service.
The layered learning practice model (LLPM), within which a pharmacist supervises both a pharmacy resident and a student, mitigates the growing demand for clinical rotations that has accompanied national expansion of Doctor of Pharmacy programs. A Canadian collaborative of hospital pharmacists established consensus on 8 clinical pharmacy key performance indicators (cpKPIs), activities associated with improved patient outcomes. Increased implementation of the LLPM alongside cpKPI measurement offers opportunities to compare the LLPM with standard practice in terms of pharmaceutical care delivery. To quantify clinical productivity, as measured by proportions of eligible patients receiving cpKPIs and absolute numbers of completed cpKPIs, across scenarios involving pharmacists working with and without pharmacy learners. In this retrospective observational study, pharmacy students, pharmacy residents, and pharmacists recorded completion of 7 cpKPIs for oncology inpatients over a total of 6 months in 2017 and 2018. Clinical productivity was described across the following 3 scenarios: presence of one or more pharmacists with one resident and one or more students (P-R-S); presence of one or more pharmacists with one or more students (P-S); and presence of one or more pharmacists only (P; standard practice). During the study, there were 685 recorded admissions to the inpatient oncology service. Generally, the proportions of patients who received cpKPIs were similar for scenarios with and without pharmacy learners present. Standardized to 20 pharmacist workdays, the total number of cpKPIs 1, 2, 3, 5, 6, and 7 (255 with P-R-S scenario, 281 with P-S scenario, and 258 with P scenario) and the total number of drug therapy problems resolved (i.e., cpKPI 3; 153 with P-R-S scenario, 180 with P-S scenario, and 149 with P scenario) were similar across the scenarios. Scenario P had fewer admitted patients per pharmacist workday (3.2) than scenarios P-S and P-R-S (3.4 and 3.7, respectively), which may have contributed to a trend toward greater proportions of patients receiving cpKPIs under scenario P. Compared with standard practice, integration of pharmacy learners within an oncology unit did not appear to impair clinical productivity, as demonstrated by the comparable proportions of patients receiving cpKPIs and the total number of completed cpKPIs.


Estimation of lung cancer risk using homology-based emphysema quantification in patients with lung nodules.
The purpose of this study was to assess whether homology-based emphysema quantification (HEQ) is significantly associated with lung cancer risk. This retrospective study was approved by our institutional review board. We included 576 patients with lung nodules (317 men and 259 women; age, 66.8 ± 12.3 years), who were selected from a database previously generated for computer-aided diagnosis. Of these, 283 were diagnosed with lung cancer, whereas the remaining 293 showed benign lung nodules. HEQ was performed and percentage of low-attenuation lung area (LAA%) was calculated on the basis of computed tomography scans. Statistical models were constructed to estimate lung cancer risk using logistic regression; sex, age, smoking history (Brinkman index), LAA%, and HEQ were considered independent variables. The following three models were evaluated: the base model (sex, age, and smoking history); the LAA% model (the base model + LAA%); and the HEQ model (the base model + HEQ). Model performance was assessed using receiver operating characteristic analysis and the associated area under the curve (AUC). Differences in AUCs among the models were evaluated using Delong's test. AUCs of the base, LAA%, and HEQ models were 0.585, 0.593, and 0.622, respectively. HEQ coefficient was statistically significant in the HEQ model (P = 0.00487), but LAA% coefficient was not significant in the LAA% model (P = 0.199). Delong's test revealed significant difference in AUCs between the LAA% and HEQ models (P = 0.0455). In conclusion, after adjusting for age, sex, and smoking history (Brinkman index), HEQ was significantly associated with lung cancer risk.


A strategy for dissecting the architectures of native macromolecular assemblies.
It remains particularly problematic to define the structures of native macromolecular assemblies, which are often of low abundance. Here we present a strategy for isolating complexes at endogenous levels from GFP-tagged transgenic cell lines. Using cross-linking mass spectrometry, we extracted distance restraints that allowed us to model the complexes' molecular architectures.


Best Practices for Preclinical In Vivo Testing of Cancer Nanomedicines.
Significant advances have been made in the development of nanoparticles for cancer treatment in recent years. Despite promising results in preclinical animal models, cancer nanomedicines often fail in clinical trials. This failure rate could be reduced by defining stringent criteria for testing and quality control during the design and development stages, and by performing carefully planned preclinical studies in relevant animal models. This article discusses best practices for the evaluation of nanomedicines in murine tumor models. First, a recommended set of experiments to perform is introduced, including discussion of the types of data to collect during these studies. This is followed by an outline of various tumor models and their clinical relevance. Next, different routes of nanoparticle administration are overviewed, followed by a summary of important controls to include in in vivo studies of nanomedicine. Finally, animal welfare considerations are discussed, and an overview of the steps involved in achieving US Food and Drug Administration approval after animal studies are completed is provided. Researchers should use this report as a guideline for effective preclinical evaluation of cancer nanomedicine. As the community adopts best practices for in vivo testing, the rate of clinical translation of cancer nanomedicines is likely to improve.


Under-diagnosis of pain by primary physicians and late referral to a palliative care team.
Under-diagnosis of pain is a serious problem in cancer care. Accurate pain assessment by physicians may form the basis of effective care. The aim of this study is to examine the association between late referral to a Palliative Care Team (PCT) after admission and the under-diagnosis of pain by primary physicians. This retrospective study was performed in the Teikyo University teaching-hospital for a period of 20 months. We investigated triads composed of 213 adult cancer inpatients who had coexisting moderate or severe pain at the initial PCT consultation, 77 primary physicians, and 4 palliative care physicians. The outcome of the present study was the under-diagnosis of pain by primary physicians with routinely self-completed standard format checklists. The checklists included coexisting pain documented independently by primary and palliative care physicians at the time of the initial PCT consultation. Under-diagnosis of pain was defined as existing pain diagnosed by the palliative care physicians only. Late referral to PCTs after admission was defined as a referral to the PCT at ≥20 days after admission. Because the two groups displayed significantly different regarding the distributions of the duration from admission to referral to PCTs, we used 20 days as the cut-off point for "late referral." Accurate pain assessment was observed in 192 triads, whereas 21 triads displayed under-diagnosis of pain by primary physicians. Under-diagnosis of pain by primary physicians was associated with a longer duration between admission and initial PCT consultation, compared with accurate pain assessment (25 days versus 4 days, p < 0.0001). After adjusting for potential confounding factors, under-diagnosis of pain by the primary physicians was significantly associated with late (20 or more days) referral to a PCT (adjusted odds ratio, 2.91; 95% confidence interval, 1.27 - 6.71). Other factors significantly associated with under-diagnosis of pain were coexisting delirium and case management by physicians with < 6 years of clinical experience. Under-diagnosis of pain by primary physicians was associated with late referral to PCTs. Shortening the duration from admission to referral to PCTs, and increasing physicians' awareness of palliative care may improve pain management for cancer patients.


Nucleocytoplasmic shuttling of JAZ, a new cargo protein for exportin-5.
Exportin-5 is a nuclear export receptor for certain classes of double-stranded RNA (dsRNA), including pre-micro-RNAs, viral hairpin RNAs, and some tRNAs. It can also export the RNA binding proteins ILF3 and elongation factor EF1A. However, the rules that determine which RNA binding proteins are exportin-5 cargoes remain unclear. JAZ possesses an unusual dsRNA binding domain consisting of multiple C2H2 zinc fingers. We found that JAZ binds to exportin-5 in a Ran-GTP- and dsRNA-dependent manner. Exportin-5 stimulates JAZ shuttling, and gene silencing of exportin-5 reduces shuttling. Recombinant exportin-5 also stimulates nuclear export of JAZ in permeabilized cells. JAZ also binds to ILF3, and surprisingly, this interaction is RNA independent, even though it requires the dsRNA binding domains of ILF3. Exportin-5, JAZ, and ILF3 can form a heteromeric complex with Ran-GTP and dsRNA, and JAZ increases ILF3 binding to exportin-5. JAZ does not contain a classical nuclear localization signal, and in digitonin-permeabilized cells, nuclear accumulation of JAZ does not require energy or cytosol. Nonetheless, low temperatures prevent JAZ import, suggesting that nuclear entry does not occur via simple diffusion. Together, these data suggest that JAZ is exported by exportin-5 but translocates back into nuclei by a facilitated diffusion mechanism.


Changes of cardiac performance in renal failure.
Clinical and experimental studies were carried out in order to evaluate the role of myocardial dysfunction in the genesis of circulatory congestion associated with renal failure. Among the patients with chronic renal failure, those with circulatory congestion had greater blood volume and higher venous pressure while lower cardiac index and stroke work index than those without circulatory congestion. After peritoneal dialysis, although blood volume and venous pressure decreased in both groups, cardiac index increased in the former while it decreased in the latter group. In 15 dogs, acute renal failure was produced by ligating both ureters. As uremia developed, blood volume and left ventricular end-diastolic pressure increased with or without an increase in cardiac index. The depression of ventricular function curve was evident in all the dogs. The peritoneal dialysis performed at this stage resulted in a prompt recovery of left ventricular end-diastolic pressure with minimum change in cardiac index. The measurement of dp/dt/IIT also indicated a depression of myocardial contractility at uremic stage and its recovery after dialysis. We conclude that impairment of myocardial function is implicated in the development of circulatory congestion in renal failure.


[Role of Staphylococcus epidermidis in outer eye infections].
Coagulase-negative staphylococci (CNS) from 57 patients with outer eye infections and healthy control eyes were isolated according to the Schleifer and Cloos classification and the sensitivity to antibiotics of the isolated CNS was examined. The pathogenicity of CNS in rabbit cornea was studied by direct inoculation of CNS. The results showed that of 57 strains of CNS, 25 strains (43.9%) belonged to S. epidermidis, 22 (38.6%) belonged to non-detectable strains, 4 (7%) belonged to S. capitis, 3 (5.3%) belonged to S. hominis and 2 (3.5%) belonged to S. saprophyticus. Furthermore these CNS were resistant to aminoglycoside and machloride antibiotics which are commonly used as eye drops for ocular infectious diseases. Control rabbit corneas inoculated with CNS almost became clear within 24 hours. Therefore, it was suggested that ocular CNS infections can occur in immunologically compromised host patients.


A prospective study assessing the effect of coronal tooth structure loss on the outcome of root canal retreatment.
To evaluate the outcome of secondary root canal treatment (retreatment) on posterior teeth in relation to the residual volume of coronal tooth structure, measured with an intraoral scanner, using periapical radiography and cone beam computed tomography (CBCT). A total of 137 posterior teeth in 121 patients were assessed clinically and radiographically using periapical radiographs and CBCT scans at baseline and 1 year after root canal retreatment. The increase or decrease in the size of preoperative periapical radiolucencies and development of new radiolucencies were assessed by a consensus panel consisting of two pre-calibrated examiners. A clinical impression was obtained for each tooth after completion of root canal retreatment, before the placement of the temporary restoration and following cast restoration placement to produce two casts. All casts were scanned using an intraoral digital scanner and the three-dimensional volume of remaining tooth structure calculated. Teeth were also classified according to the number of remaining coronal walls before core build-up. χ2 test was used to determine the association between the outcome of root canal retreatments and the volume of remaining coronal tooth structure. At the 1-year recall, teeth retaining less than 30% of their original tooth structure volume had a significantly higher proportion of unfavourable outcomes (χ2 , P < 0.05, odds ratio [OR], 2.58; 95% CI, 1.026-6.487). The loss of tooth structure volume is an objective parameter that can be used to predict the probability of success of root canal retreatments. At 1-year follow-up, the percentage of unfavourable outcomes of root canal retreated teeth was significantly higher when less than 30% of the original tooth tissue structure was present at baseline.


Antibody-derived in vivo imaging of tau pathology.
Antibodies or their derivatives as imaging probes for pathological tau protein have great potential, but have not been well studied. In particular, smaller, single-chain-variable antibody fragments (scFv's) are attractive for detecting tau lesions in live subjects. Here, we generated libraries of scFv's and identified numerous phospho-tau-selective scFv's. Peripheral injection of one of these scFv's consistently resulted in a strong in vivo brain signal in transgenic tauopathy mice, but not in wild-type or amyloid-β plaque mice. The parent tau antibody provided similar results, albeit with a weaker signal intensity. The imaging signal correlated very well with colocalization of the probe with intraneuronal tau aggregates. Both were associated with markers of endosomes, autophagosomes, and lysosomes, suggesting their interaction in these degradation pathways. Such specific antibody-derived imaging probes have great potential as diagnostic markers for Alzheimer's disease and related tauopathies.


[Expression of HLA class II antigen-associated invariant chain on renal cell cancer].
Major histocompatibility complex (MHC) antigens play important roles in immune responses. MHC class II molecules serve as restriction elements for cells presenting antigens to CD4-positive helper T-cells. They also function as histocompatibility antigens responsible for graft rejections by stimulating allogenic reaction. Furthermore, it was reported that the expression of class II antigen on tumor cells increases immunogenicity in mice by a mechanism involving class II molecule positive tumor cells which present tumor associated antigens to host immune cells or induce allogenic reactions against tumor cells. Class II molecules associate with the HLA class II antigen-associated invariant chain (Ii) as soon as class II molecules are produced in the rough endoplasmic reticulum. Ii is considered to block the binding of endogenous peptides to class II molecules, and to be a signal for transporting class II molecules to endosomes. Both functions of Ii are essential for the function of class II molecules. To investigate the association between renal cell cancer (RCC) and the host's immune system, we immunohistochemically examined 60 RCCs for the expression of Ii, class II and class I antigens on RCC and the degree of lymphocytic infiltration. We detected Ii to varying degrees on 53 out of 60 RCC tissues but none on normal renal tubular cells. Compared with class II antigens, they were detected in the order DR > or = Ii > or = DP not equal to DQ. A significant correlation was found between the expression of Ii and the degree of lymphocytic infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein-Bound β-glucan from Coriolus Versicolor has Potential for Use Against Obesity.
The prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, it has been shown that one protein-bound β-glucan (PBG) from the edible mushroom Coriolus versicolor can be a potent anti-obesity component. PBG can reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis reveals that PBG markedly increases the abundance of Akkermansia muciniphila, although it does not rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appears that PBG alters host physiology and creates an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduce obesity in recipient HFD-fed mice. Further, PBG is shown to upregulate expression of a set of genes related to host metabolism in microbiota-depleted mice. The data highlight that PBG may exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of host metabolism) manner. The fact that C. versicolor PBGs are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate PBG as a novel use for obesity treatment.


Imaging findings of gastric diverticula.
Gastric diverticula (GD) are very rare. Computer tomographic findings in GD have been reported only as case reports previously. The aim of this study was to estimate the prevalence of GD on computed tomography (CT) and to analyze their radiological appearances. From 2006 to 2013, a total of 14,428 patients were examined by abdominal/thoracic CT at our institution. GD were diagnosed in 18 (0.12%) patients (13 women and 5 men, median age, 64 years). In 9 patients, additional endoscopy and in 7 patients upper gastrointestinal investigation with contrast medium were performed. Magnetic resonance imaging (MRI) was available for 3 cases. In all patients GD were diagnosed incidentally during CT examination. The diverticula were located at the posterior wall of the gastric fundus below the esophagogastric junction. On CT, GD presented as cystic lesions with a thin wall and an air fluid level, located behind the stomach between spleen, adrenal gland, and crus of the left diaphragm. The prevalence of GD encountered in our CT series is 0.12%. GD demonstrate typical CT appearances, namely, cystic lesions located in the left paravertebral region. The radiologist should be familiar with this finding to avoid possible misinterpretations.


Primary Hydatid Cyst of the Diaphragm Mimicking Diaphragmatic Tumour: A Case Report.
Echinococcus commonly affects the liver and the lung, but several organs can be affected by this disease. The isolated primary diaphragmatic hydatid cyst, not associated with liver or lung, is very rare. We report a case of hydatid cyst in a 55-year-old male, located in the abdominal side of the left hemidiaphragm which mimicked a hypovascular diaphragmatic tumour and exophytic splenic cyst. In our case the diagnosis was confirmed only with histopathological examination done after surgical excision of the cyst. The aim of this work lies in the fact that knowledge of this clinical entity especially in endemic areas as in India will enable radiologists to guide the clinicians in proper diagnosis and adequate pre-operative planning.


Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review.
Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics. To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations. We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction. A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL. Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.


Evaluation of a mass measles immunisation campaign in a rapidly growing peri-urban area.
A mass measles immunisation campaign, with a target coverage rate of 85-90%, was launched in Khayelitsha, a rapidly growing urban township in the Cape Town area. Cross-sectional surveys of the measles immunisation status of resident 6-23-month-old infants were conducted immediately before, immediately after, and approximately 2 months after the campaign in order to determine the effectiveness of a mass campaign in boosting coverage in an area with a high influx rate. Immunisation coverage rates were 55% in the first survey, 76% in the second, and 72% in the third. In the first survey, coverage rates for children born in Cape Town were 1.4 times higher than those born elsewhere. This trend continued throughout the survey. Duration of stay in Cape Town also influenced coverage, with rates for the recently arrived children being considerably lower than those for the more established Cape Town residents. The influx rate between the second and third survey (over the Christmas period) was 9.1% per month. Failure to reach the targeted rate is attributed to the influx rate, campaign design and implementation, and factors related to child and career mobility. Alternative immunisation strategies, with social awareness playing a key role, are being urgently investigated.


Fused Multifunctionalized Chromenes from Tetraynes and α,β-Unsaturated Aldehydes.
The synthesis of fused, highly substituted chromenes in a one-pot-three-step cascade hexadehydro-Diels-Alder reaction of tetraynes followed by an intermolecular α,β-unsaturated aldehyde rearrangement is reported. The target compounds were prepared by the condensation of malonates with 3-bromo-1-propyne, and the resulting 2,2-di(1-propyn-3-yl)malonates underwent cross-coupling with phenylethynyl bromides to afford 2,2-di(5-phenyl-2,4-pentadiynyl)malonates, which underwent intramolecular cyclization to produce tricyclic chromenes. The overall transformation involves the formation of four new C-C bonds and one new C-aryl-O-C-aryl bond by both intramolecular cyclization and intermolecular rearrangement reactions. These constitute a key strategy for the construction of a highly substituted natural chromene core and a robust method for producing other chromenes.


An outbreak of Oropouche virus diease in the vicinity of santarem, para, barzil.
An epidemic of human febrile illness caused by Oropouche virus was studied in the village of Mojui dos Campos, Pará State, in February 1975. The major clinical symptoms, fever, chills, headache, myalgia, arthralgia and dizziness persisted for 2 to 7 days. Leukopenia was commonly observed. Some patients were severely ill but no deaths were attributed to the disease. Recurrence of symptoms was reported in several people. 55 cases of recent infection were diagnosed in Mojuí dos Campos between February and April. In the same period 26 cases were recorded from the Palhal area, near to Mojuí. Two additional cases were observed, one in the small settlement of Terra Preta and the other in the town of Santarém, which are 12 and 20 km from Mojuí, respectively. Of the 83 infections, 65 were proven by virus isolation from the blood of patients and 18 by the demonstration of an increasing antibody level to the agent. Both sexes of the population were infected in equal proportions. Most patients were below 20 years of age. In the village of Mojuí dos Campos with a population of about 2,900, 45 (40,1%) out of 112 students aged 4 to 18, had HI antibodies to the virus when examined late in February. The epidemic, however, only declined after the middle of March. Two isolations of Oropouche virus were obtained from some 15,000 Culicoides inoculated into mice. About 4,000 Culicoides and all the 9,420 mosquitoes captured during the outbreak remain to be inoculated. Over 95% of the Culicoides were C. paraensis. Only 1 rodent of the genus Proechimys had HI antibodies to Oropouche virus out of the 602 wild and domestic mammals captured in the area. All 5 reptiles examined were negative. 34 (4.9%) out of the 681 wild birds and 12 (5.8%) out of the 206 domestic birds examined were positive for the presence of HI antibodies to the agent.


The impact of alcohol-related admissions on resource use in critically ill patients from 2009 to 2015: an observational study.
Excessive alcohol use is associated with increased health care utilisation and increased mortality. This observational study sought to identify the proportion of patients admitted with a critical illness in which alcohol misuse contributed, and to examine the resource use for this group. We performed an observational retrospective database review of all admissions to the Alice Springs Hospital intensive care unit (ICU) between 1 January 2009 and 31 December 2015. The Alice Springs Hospital ICU is a ten-bed unit located in Central Australia, with approximately 600 admissions annually. The per capita consumption of alcohol in Central Australia is approximately 1.5 times the national average. The primary aim was to determine the proportion of admissions to intensive care in which alcohol misuse was identified as a contributing cause. Secondary aims examined resource utilisation including ICU and hospital length of stay, need for and duration of mechanical ventilation, and ICU re-admission. There were 3,768 admissions involving 2,670 individual patients. Of these admissions 947 (25%) were associated with alcohol misuse. Admissions associated with alcohol were significantly more likely to require mechanical ventilation (30% versus 20%, P <0.01), and had a significantly longer ICU length of stay (2.1 versus 1.9 days, P <0.05). The proportion of admissions in which alcohol misuse was implicated is amongst the highest in the published literature. The results of this study should drive further policy change directed at harm minimisation, and warrant more detailed epidemiological work at both a local and national level.


[Acute Ventilatory Failure during Prone Thoracoscopic Esophagectomy with Carbon Dioxide Insufflation in a Patient Managed by a Single Lumen Tracheal Tube].
A 67-year-old woman underwent prone thoracoscopic esophagectomy with carbon dioxide (CO2) insufflation. After insertion of an epidural catheter, general anesthesia was induced with propofol, sevoflurane, remifentanil and rocuronium. The trachea was intubated with a single lumen endotracheal tube (SLET). CO2 insufflation at 5 mmHg with the SLET deflated the right lung and provided excellent visualization without respiratory instability. The left side pleura was injured during the inferior mediastinal lymphadenectomy and the patient went into sudden profound hypoventilation with an increase in end-tidal CO2 from 43 to 64 mmHg. We observed the trachea with bronchofiberscope and the SLET was correctly located and not obstructed. We were convinced that bilateral pneumothorax occurred because the left side pleura was injured and auscultation revealed decreased breath sounds over the left hemithorax. We asked the surgeon to discontinue the insufflated CO2 and both lungs were fully expanded. The operation was then carried out successfully without further untoward event. The patient was successfully extubated at the intensive care unit on postoperative day 1. The CO2 insufflation during thoracoscopic esophagectomy can cause bilateral pneumothorax and we recommend to inflate the bilateral lungs regularly for the continuation of the surgery.


Objective measurements of sleep for non-laboratory settings as alternatives to polysomnography--a systematic review.
Sleep disturbance influences human health. To examine sleep patterns, it is advisable to utilize valid subjective and objective measures. Laboratory-based polysomnography (PSG) is deemed the gold standard to measure sleep objectively, but is impractical for long-term and home utilization (e.g. resource-demanding, difficult to use). Hence, alternative devices have been developed. This study aimed to review the literature systematically, providing an overview of available objective sleep measures in non-laboratory settings as an alternative to PSG. To identify relevant articles, a specific search strategy was run in EMBASE, PubMed, CINAHL, PsycInfo and Compendex (Engineering Village 2). In addition, reference lists of retrieved articles were screened and experts within this research field were contacted. Two researchers, using specified in/exclusion criteria, screened identified citations independently in three stages: on title, abstract and full text. Data from included articles were extracted and inserted into summarizing tables outlining the results. Of the 2217 electronically identified citations, 35 studies met the inclusion criteria. Additional searches revealed eight papers. Psychometric characteristics of nine different objective measures of sleep pattern alternatives to PSG [(bed) actigraphy, observation, bed sensors, eyelid movement- and non-invasive arm sensors, a sleep switch and a remote device] were evaluated. Actigraphy is used widely and has been validated in several populations. Alternative devices to measure sleep patterns are becoming available, but most remain at prototype stage and are validated insufficiently. Future research should concentrate on the development and further validation of non-invasive, inexpensive and user-friendly sleep measures for non-laboratory settings.


A practical approach for applying best practices in behavioural interventions to injury prevention.
Behavioural science when combined with engineering, epidemiology and other disciplines creates a full picture of the often fragmented injury puzzle and informs comprehensive solutions. To assist efforts to include behavioural science in injury prevention strategies, this paper presents a methodological tutorial that aims to introduce best practices in behavioural intervention development and testing to injury professionals new to behavioural science. This tutorial attempts to bridge research to practice through the presentation of a practical, systematic, six-step approach that borrows from established frameworks in health promotion and disease prevention. Central to the approach is the creation of a programme theory that links a theoretically grounded, empirically tested behaviour change model to intervention components and their evaluation. Serving as a compass, a programme theory allows for systematic focusing of resources on the likely most potent behavioural intervention components and directs evaluation of intervention impact and implementation. For illustration, the six-step approach is applied to the creation of a new peer-to-peer campaign, Ride Like a Friend/Drive Like You Care, to promote safe teen driver and passenger behaviours.


A new n-type low bandgap conjugated polymer P-co-CDT: synthesis and excellent reversible electrochemical and electrochromic properties.
A n-type low bandgap conjugated polymer based on perylene diimide and cyclopenta[2,1-b:3,4-b']dithiophene, which exhibits excellent reversible electrochemical properties in both n-doping/dedoping and p-doping/dedoping processes, was designed, synthesized and characterized.


Localized Notch signal acts through eyg and upd to promote global growth in Drosophila eye.
Notch (N) signal is activated at the dorsoventral (DV) border of the Drosophila eye disc and is important for growth of the eye disc. In this study, we showed that the Pax protein Eyg is a major effector mediating the growth promotion function of N. eyg transcription is induced by N signaling occurring at the DV border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be compensated by overexpressing eyg, whereas loss of the downstream eyg blocked the function of N signaling. In addition, we showed that N and eyg could induce expression of upd, which encodes the ligand for the Jak/STAT pathway and acts over long distance to promote cell proliferation. Loss of eyg or N can be compensated by overexpressing upd. These results suggest that upd is a major effector mediating the function of eyg and N. The functional link from N to eyg to upd explains how the localized Notch activation can achieve global growth control.


Enhancing the Washing Durability and Electrical Longevity of Conductive Polyaniline-Grafted Polyester Fabrics.
The demand for wearable electronics has driven the development of conductive fabrics, particularly those incorporating polyaniline (PANI) that is known for its high electrical conductivity, flexibility, and ease of fabrication. However, the limited stability and durability of the conductive fabric, especially during washing, present significant challenges. The drawbacks can be traced by weak physical attachment between the fabric and the conductive coating, leading to a decrease in conductivity over time. These drawbacks significantly impact the fabric's functionality and performance, highlighting the need for effective solutions to enhance its stability and durability. This study focuses on addressing these challenges by employing a thermochemical treatment. A hydrophilic surface of the polyester fabric is obtained after the treatment (hydrolysis), followed by grafting of PANI on it. The adhesion between PANI and the polyester fabrics was found to be enhanced, as proved by contact angle analysis. Furthermore, the PANI-hydrolyzed fabrics (treated) demonstrated stable conductivity (∼10-3 S cm-3) even after 10 washing cycles, showcasing their excellent durability. In comparison, the unhydrolyzed PANI fabric experienced a drop in conductivity by three orders of magnitude. X-ray photoelectron spectroscopy via N 1s core line spectra showed chemical shifts and quantified the level of doping through PANI's protonation level. We found that PANI-hydrolyzed fabrics preserved their dedoping level from 44.77 to 42.68%, indicating improved stability and extension of their electrical properties' lifetime after washing as compared to unhydrolyzed (untreated) fabrics, from 36.99 to 26.61%. This investigation demonstrates that the thermochemical approach can effectively enhance the durability of conductive PANI fabrics, enabling them to withstand the washing process while preserving their electrical endurance.


The role and safety of UVA and UVB in UV-induced skin erythema.
Different wavelengths of ultraviolet (UV) light cause skin damage through different mechanisms. Minimal erythema dose (MED) is usually used to clinically evaluate skin sensitivity to ultraviolet radiation by inducing skin erythema using ultraviolet B (UVB) or ultraviolet A (UVA) + UVB. In this study, we detected changes in the blood flow at the MED erythema caused by UVB and UVA + UVB radiation through optical coherence tomography (OCT) to explain the role of different bands of ultraviolet rays in erythema induction. Two MED irradiation areas on the subjects' back were irradiated with UVB alone or UVA + UVB (UVA: UVB = 8:1). The absolute energy of UVB remained the same in UVB and UVA+UVB. At 24 h after the irradiation, the changes in the blood flow in the MED area were detected using OCT. Compared with the blank control, the maximum blood flow depth, blood flow peak, and total blood flow of UVB-MED and UVA+UVB-MED were significantly increased. Notably, the maximum blood flow depth and blood flow peak of UVB-MED were higher than UVA+UVB-MED. There was no significant difference in total blood perfusion between UVA+UVB-MED and UVB-MED. Under the same UVB energy, the skin erythema caused by UVA + UVB was weaker than UVB alone. The analysis of local blood flow by OCT showed that the peak and maximum depth of local blood flow caused by UVB alone were significantly higher than UVA + UVB.


The psychological refractory period effect following callosotomy: uncoupling of lateralized response codes.
A callosotomy patient was tested in 2 dual-task experiments requiring successive speeded responses to lateralized stimuli. The patient showed a robust psychological refractory period (PRP) effect. Three aspects of the data indicate that, unlike for the control participants, the PRP effect for the split-brain patient should not be attributed to a response selection bottleneck. First, the patient did not show an increase in reaction time (RT) when the 2 tasks required responses from a common output system compared with when different output systems were used. Second, inconsistent stimulus-response mappings for the 2 tasks increased RTs for the control participants but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with stimulus onset asynchrony but was additive or overadditive for the normal participants. These results suggest that the persistent PRP effect following callosotomy should be attributed to a bottleneck associated with response initiation, a strategy adopted to comply with the task demands, or a combination of these factors.


[Intraoperative floppy iris syndrome--a prospective study].
is to evaluate the incidence and typical signs of floppy iris syndrome intraoperatory revealed in patients diagnosed with cataracts. We studied a total of 15 eyes diagnosed with cataracts, belonging to 14 patients who had been treated chronically with Tamsulosin for benign prostatic hyperplasia. In 80% of cases we have seen a preoperative semimidriasis which required iris hooks in 5 eyeballs. On 1 eye preoperative semimidriasis was sufficient for capsulorhexis, but later pupil became miotic, requiring iris hooks. On 4 eye flaccid iris was noticed, that prolabated in corneal incision. floppy iris syndrome occurs in patients treated with Tamsulosin for benign prostatic hyperplasia, generating a series of difficulties during cataract surgery.


Visual Mismatch Negativity Reflects Enhanced Response to the Deviant: Evidence From Event-Related Potentials and Electroencephalogram Time-Frequency Analysis.
Automatic detection of information changes in the visual environment is crucial for individual survival. Researchers use the oddball paradigm to study the brain's response to frequently presented (standard) stimuli and occasionally presented (deviant) stimuli. The component that can be observed in the difference wave is called visual mismatch negativity (vMMN), which is obtained by subtracting event-related potentials (ERPs) evoked by the deviant from ERPs evoked by the standard. There are three hypotheses to explain the vMMN. The sensory fatigue (or refractoriness) hypothesis considers that weakened neural activity caused by repetition results in decreased ERPs of the standard. The memory trace hypothesis proposes that vMMN results from increased responses to the deviant. The predictive coding hypothesis attributes the difference to enhanced responses for deviants and suppression for standards. However, when distinguishing between these effects, previous researchers did not consider the effect of low-level features on the vMMN. In this experiment, we used face sequences composed of different emotions (e.g., neutral and fearful face) and presented an oddball sequence, a reverse oddball sequence, and an equiprobable sequence to participants. The deviant of the oddball sequence was subtracted from the standard of the oddball sequence, the reverse oddball sequence, and the same type of stimulus of the equiprobable sequence to get oddball-vMMN (vMMN1), reverse oddball-vMMN (vMMN2), and equiprobable-vMMN (vMMN3), respectively. The results showed no significant difference between vMMN2 and vMMN3 in 100-350 ms following stimulus onset, while the vMMN effect was significant, indicating that the probability of the standard did not affect vMMN, which supported the memory trace hypothesis. Additionally, the fearful-related vMMN were more negative than the neutral-related vMMN within the range of 100-150 ms, suggesting a negative bias. We analyzed the source location of different vMMNs. There was no significant difference in brain regions between different vMMNs. Time-frequency analysis showed that the deviant had stronger theta-band oscillatory than the standard (visual mismatch oscillatory responses, vMORs). However, there was no difference between vMORs2 and vMORs3, indicating that vMORs reflect an enhanced response to the deviant in terms of neural oscillation, supporting the memory trace hypothesis.


Effects of ractopamine hydrochloride on growth performance, carcass characteristics, and physiological response to different handling techniques.
Feedlot cattle ( = 128; BW = 549 ± 60 kg) were used to evaluate the effects of ractopamine hydrochloride (RAC) on growth performance, physiological response to handling, and mobility during shipment for slaughter in a study utilizing a split-plot design with a 2 × 2 factorial arrangement of treatments: 1) diet (CON [no β-adrenergic agonist] vs. RAC [400 mg·animal·d ractopamine hydrochloride for 28 d]) and 2) handling intensity (HI; low-stress handling [LSH; cattle moved at a walking pace with no electric prod use] vs. high-stress handling [HSH; cattle moved at a minimum of a trot and an electric prod applied while in the alley for posthandling restraint and during loading for shipment to the abattoir]). Cattle fed RAC tended to have greater ADG and G:F ( = 0.06), and had greater HCW and LM area ( = 0.04). The HI treatments were applied on the day after the 28-d growth performance period. Blood samples were collected before HI treatment (baseline), after HI treatments (POSTHAND), after transport to the abattoir (POSTTRANS), and during exsanguination at slaughter. A diet × HI interaction ( = 0.01) was observed in the change in cortisol from baseline to POSTTRANS, and there tended ( ≤ 0.07) to be diet × HI interactions for the change in epinephrine from baseline to POSTHAND and for the change in creatine kinase (CK) from baseline to POSTTRANS. Feeding RAC and HSH both increased the change from baseline to POSTHAND in norepinephrine and pH ( ≤ 0.05). The HSH cattle also had greater changes from baseline to POSTHAND in blood HCO, base excess, partial pressure of CO, lactate, cortisol, and glucose ( ≤ 0.01). Ractopamine and HSH both produced greater increases in CK concentrations from baseline to slaughter ( < 0.01). Mobility was not affected by RAC at the feedlot or following an average 6-h lairage ( ≥ 0.43). This study confirms RAC improves growth performance and suggests metabolic acidosis, a precursor to fatigued cattle syndrome, develops in cattle allowed to trot without the use of a lead rider regardless of RAC administration. Cattle fed RAC displayed altered hormonal responses to handling and transport stress, and the overall proportion of cattle with compromised mobility appears to increase later in the marketing channel. These findings warrant additional research aimed at better understanding the physiological response to stress and protect the welfare of cattle during shipment for slaughter.


Sublethal Hyperthermia Transiently Disrupts Cortisol Steroidogenesis in Adrenocortical Cells.
Primary aldosteronism is the most common cause of secondary hypertension. The first-line treatment adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone-producing adenomas, while preserving adjacent normal adrenal cortex. To determine the extent of damage to adrenal cells upon exposure to hyperthermia, the steroidogenic adrenocortical cell lines H295R and HAC15 were treated with hyperthermia at temperatures between 37 and 50°C with the effects of hyperthermia on steroidogenesis evaluated following stimulation with forskolin and ANGII. Cell death, protein/mRNA expression of steroidogenic enzymes and damage markers (HSP70/90), and steroid secretion were analyzed immediately and 7 days after treatment. Following treatment with hyperthermia, 42°C and 45°C did not induce cell death and were deemed sublethal doses while ≥50°C caused excess cell death in adrenal cells. Sublethal hyperthermia (45°C) caused a significant reduction in cortisol secretion immediately following treatment while differentially affecting the expression of various steroidogenic enzymes, although recovery of steroidogenesis was evident 7 days after treatment. As such, sublethal hyperthermia, which occurs in the transitional zone during thermal ablation induces a short-lived, unsustained inhibition of cortisol steroidogenesis in adrenocortical cells in vitro.


Self-trapping of dark incoherent light beams
"Dark beams" are nonuniform optical beams that contain either a one-dimensional (1D) dark stripe or a two-dimensional (2D) dark hole resulting from a phase singularity or an amplitude depression in their optical field. Thus far, self-trapped dark beams (dark solitons) have been observed using coherent light only. Here, self-trapped dark incoherent light beams (self-trapped dark incoherent wavepackets) were observed. Both dark stripes and dark holes nested in a broad partially spatially incoherent wavefront were self-trapped to form dark solitons in a host photorefractive medium. These self-trapped 1D and 2D dark beams induced refractive-index changes akin to planar and circular dielectric waveguides. The experiments introduce the possibility of controlling high-power coherent laser beams with low-power incoherent light sources such as light emitting diodes.


[Clear diagnosis in an atypical case of bronchial asthma and treatment monitoring using pulmonary function tests].
The paper deals with a bronchial asthma case whose anamnesis and clinical data plead rather for a chronic obstructive bronchitis (COPD). The diagnosis is elucidated through the pulmonary function tests performed both before and after a treatment which suppresses the inflammation and oedema of the mucous membrane with hypercrinia and discrinia, thus allowing the hyperreactivity of bronchial smooth muscles to become evident. Taking into account that more than 50% of the asthmatic persons have not a correct perception of the airway obstruction, treatment effect evaluation on the basis of clinical data only may lead to an early treatment stepping which can favour the development of a chronic inflammation and a "basic" obstructive syndrome resulting in a pulmonary insufficiency later on. Pulmonary function tests are therefore useful in monitoring the treatment whose efficacy is proved by the achievement of normal pulmonary function (or at least as close to normal as possible) and not only by the suppression of clinical symptoms.


From trauma-blind to trauma-informed: re-thinking criminalization and the role of trauma in persons with serious mental illness.
Trauma-informed approaches offer a new perspective for understanding how and why individuals with serious mental illness (SMI) become entangled in the criminal justice system. There is growing awareness that many individuals with SMI have experienced significant life trauma, and factors beyond SMI that contribute to criminalization are being identified; however, the role of trauma continues to be overlooked in many formulations. In trauma-blind systems, trauma-related behaviors are often misunderstood and met with responses that exacerbate psychiatric and behavioral problems. Trauma-informed approaches provide a richer understanding of underlying drivers of behavior, and view trauma as an integral component of risk management, case formulation, relationship-based care, and referral. Embedding trauma-informed principles across organizations promotes continuity of care, safety, and more compassionate cultures that help reduce the flow of individuals with SMI into the criminal justice system. An expanded view of the criminalization hypothesis is offered, which incorporates all factors addressed in current research.


Selenium alleviates phytotoxicity of phenanthrene and pyrene in Alternanthera Philoxeroides.
To investigate if selenium can alleviate phytotoxicity of phenanthrene and pyrene, two high molecular weight (HMW) PAHs (polycyclic aromatic hydrocarbons) in Alternanthera philoxeroides are considered. A 60-day pot-culture experiment was carried out to assess the effects of selenium (0.5 mg Se·kg-1 soil) on A. philoxeroides exposed to two PAH pollutants, pyrene (PYR) and phenanthrene (PHE), at levels of 10, 100, and 1000 mg·kg-1. The test index included growth, chlorophyl, gas exchange and chlorophyl fluorescence parameters, and indicators of oxidative stress (H2O2 and malondialdehyde MDA). The response of plants to PAH exposure was concentration dependent; indicators of plant health declined, while indicators of plant stress rose. The maximum values of H2O2 and MDA were recorded at 1000 mg·kg-1 PYR, followed by 1000 mg·kg-1 PHE. However, application of Se (0.5 mg·kg-1) to the soil significantly decreased the phytotoxic response to PAH exposure. This study demonstrated that Se increases the tolerance of A. philoxeroides to PYR and PHE, improving the feasibility of phytoremediating high level PAH contamination and expediting ecological restoration.


[Yersinia enterocolitica serotype O:8 infections at the Hirosaki district in Aomori Prefecture from 1984 to 1991].
During the period from January 1984 to December 1991, 118 strains of Yersinia enterocolitica were isolated from the specimens which were requested for bacterial examination from various medical practitioners. The results of bacteriological examination of these isolates showed that 11 of Y. enterocolitica serotype O:8 sporadic infections were confirmed at Hirosaki district in Aomori Prefecture. Of the eleven isolated strains, nine were from feces, two were from contents of extracted appendix. These strains were biovar (Wauters) 1, harboring 42 megadalton virulence plasmid, positive for autoagglutination and calcium dependency. Patients were under fifteen years old except one case of a 45 year old. Seven patients were living in the inter-mountain area, three in the urban area and one in the plain area. The infectious source was not found.


(Carboxymethyl)chitosan-modified superparamagnetic iron oxide nanoparticles for magnetic resonance imaging of stem cells.
Magnetic resonance imaging (MRI) is emerging as a powerful tool for in vivo noninvasive tracking of magnetically labeled stem cells. In this work, we present an efficient cell-labeling approach using (carboxymethyl)chitosan-modified superparamagnetic iron oxide nanoparticles (CMCS-SPIONs) as contrast agent in MRI. The CMCS-SPIONs were prepared by conjugating (carboxymethyl)chitosan to (3-aminopropyl)trimethoxysilane-treated SPIONs. These nanoparticles were internalized into human mesenchymal stem cells (hMSCs) via endocytosis as confirmed by Prussian Blue staining and electron microscopy investigation and quantified by inductively coupled plasma mass spectrometry. A MTT assay of the labeled cells showed that CMCS-SPIONs did not possess significant cytotoxicity. In addition, the osteogenic and adipogenic differentiations of the hMSCs were not influenced by the labeling process. The in vitro detection threshold of cells after incubation with 0.05 mg/mL of CMCS-SPIONs for 24 h was estimated to be about 40 cells. The results from this study indicate that the biocompatible CMCS-SPIONs show promise for use with MRI in visualizing hMSCs.


Comprehensive Approach for Managing the Older Person with Diabetes Mellitus.
Care of the elderly population with diabetes may not be restricted to the management of hyperglycemia, associated risk factors, and specific diabetic complications. An integrated approach should also include the assessment and management of gerontological problems. Both diabetes mellitus and aging interact toward the direction of the increased incidence of geriatric syndromes. Education is a common element of both diabetes control and geriatric syndrome care. However, it has been perceived that conventional education programs for diabetics are not as effective for the elderly. We have designed geriatric reinforced education (GRE) for application in older diabetics with geriatric syndromes. We observed that the application of GRE improved the glucose control and the status of geriatric syndromes in older adults with diabetes. In summary, in terms of integrating the care of coexisting diabetes and geriatric problems, GRE may be a beneficial tool for the management of older adults with diabetes.


Comparison of the Diagnostic Image Quality of the Canine Maxillary Dentoalveolar Structures Obtained by Cone Beam Computed Tomography and 64-Multidetector Row Computed Tomography.
The objective of this blinded study was to validate the use of cone beam computed tomography (C) for imaging of the canine maxillary dentoalveolar structures by comparing its diagnostic image quality with that of 64-multidetector row CT Sagittal slices of a tooth-bearing segment of the maxilla of a commercially purchased dog skull embedded in methylmethacrylate were obtained along a line parallel with the dental arch using a commercial histology diamond saw. The slice of tooth-bearing bone that best depicted the dentoalveolar structures was chosen and photographed. The maxillary segment was imaged with cone beam CT and 64-multidetector row CT. Four blinded evaluators compared the cone beam CT and 64-multidetector row CT images and image quality was scored as it related to the anatomy of dentoalveolar structures. Trabecular bone, enamel, dentin, pulp cavity, periodontal ligament space, and lamina dura were scored In addition, a score depicting the evaluators overall impression of the image was recorded. Images acquired with cone beam CT were found to be significantly superior in image quality to images acquired with 64-multidetector row CT overall, and in all scored categories. In our study setting cone beam CT was found to be a valid and clinically superior imaging modality for the canine maxillary dentoalveolar structures when compared to 64-multidetector row CT.


Updates in Tumor Profiling in Gastrointestinal Cancers.
In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.


The reduction of platinum(IV) and palladium(IV) ions by 2,6-pyridinedihydroxamic acid.
Reaction of K(2)[Pt(IV)Cl(6)] and K(2)[Pd(IV)Cl(6)] with 2,6-pyridinedihydroxamic acid (2,6-pyha) and its disodium salt, 2,6-pyhaNa(2), yielded not the desired Pt(IV) and Pd(IV) 2,6-pyridinedihydroxamato complexes, but rather the Pt(II) and Pd(II) 2,6-pyridinedicarboxylato complexes, trans-[Pt(II)(2,6-pyca(H-1))(2)].2H(2)O and trans-[Pd(II)(2,6-pyca(H-1))(2)].2H(2)O respectively (2,6-pyca = 2,6-pyridinedicarboxylic acid). Thus in the presence of Pt(IV) and Pd(IV), the dihydroxamic acid was adventitiously hydrolysed to the corresponding dicarboxylic acid and Pt(IV) and Pd(IV) reduced to Pt(II) and Pd(II) in situ. The X-ray crystal structures of 2,6-pyha, 2,6-pyhaNa(2).8H(2)O, trans-[Pt(II)(2,6-pyca(H-1))(2)].2H(2)O and trans-[Pd(II)(2,6-pyca(H-1))(2)].2H(2)O are reported, together with a possible mechanism for the metal-assisted hydrolysis of the dihydroxamic acid and reduction of Pt(IV) and Pd(IV) to Pt(II) and Pd(II) respectively.


Atropisomerism in medicinal chemistry: challenges and opportunities.
Atropisomerism is a dynamic type of axial chirality that is ubiquitous in medicinal chemistry. There are several examples of stable atropisomeric US FDA-approved drugs and experimental compounds, and in each case the atropisomers of these compounds possess drastically different biological activities. Rapidly interconverting atropisomerism is even more prevalent, and while such compounds are typically considered achiral, they bind their protein targets in an atroposelective fashion, with the nonrelevant atropisomer contributing little to the desired activities. It has been recently demonstrated that various properties of an interconverting atropisomer can be modulated through the synthesis of atropisomer stable and pure analogs. Herein we discuss examples of atropisomerism in drug discovery as well as challenges and opportunities moving forward.


Fundamentals in Biostatistics for Research in Pediatric Dentistry: Part I - Basic Concepts.
The purpose of this report was to provide the reader with some basic concepts in order to better understand the significance and reliability of the results of any article on Pediatric Dentistry. Currently, Pediatric Dentists need the best evidence available in the literature on which to base their diagnoses and treatment decisions for the children's oral care. Basic understanding of Biostatistics plays an important role during the entire Evidence-Based Dentistry (EBD) process. This report describes Biostatistics fundamentals in order to introduce the basic concepts used in statistics, such as summary measures, estimation, hypothesis testing, effect size, level of significance, p value, confidence intervals, etc., which are available to Pediatric Dentists interested in reading or designing original clinical or epidemiological studies.


MP2 study on adsorption of hydrated Na+ and Au+ cations on the Au(111) surface.
The interactions of Na+ and Au+ cations with an Au(111) surface in the presence and absence of water molecules were investigated using Au18 and Au22 cluster models and the MP2 method with a triple-zeta valence basis set. The interactions between Na+ ions and the Au(111) surface were found to be primarily electrostatic, contrary to the much stronger Au+-Au(111) interactions that were dominated by orbital contributions. The largest CP-corrected MP2 adsorption energies were -156.9 kJ/mol for Na+ and -478.7 kJ/mol for Au+. When hydrated, Na+ prefers to be completely surrounded by water molecules rather than adsorbed to the surface, whereas Au+ remains adsorbed to the surface as water molecules bond with each other and with the Au surface. CP correction did not change the relative adsorption energy trends of Na+ or Au+ ions, but it had an effect on the interaction energy trends of the hydrated cations because of the weak water-surface and water-water interactions.


Inhibition of the lysis of fungi by melanins.
Evidence is presented that the resistance of Aspergillus nidulans hyphae to lysis by a beta-(1-->3) glucanase-chitinase mixture results from the presence of melanin in the fungal walls. The resistance of the walls to digestion was directly correlated with the melanin content of the mycelium. A melanin-less mutant of A. nidulans was highly susceptible to hydrolysis by the enzyme mixture. Preincubation of a synthetic melanin with the glucanase, chitinase, and a protease, before addition of the substrate, resulted in a marked inhibition of the rate of substrate hydrolysis. Melanin also appeared to combine with and protect at least certain substrates from decomposition, as indicated by the direct relationship between the extent of inhibition of casein hydrolysis by a bacterial protease and the length of time the protein was incubated with the melanin prior to addition of the enzyme. Melanin was found to be highly resistant to microbial degradation, a likely requirement for the polyaromatic to be effective in protecting fungal structures from lysis or decomposition by natural communities of microorganisms.


Meat Consumption and Risk of Metabolic Syndrome: Results from the Korean Population and a Meta-Analysis of Observational Studies.
Many studies have reported harmful effects of red meat or processed meat on chronic diseases including cancer and diabetes, but epidemiological evidence for metabolic syndrome is limited and remains controversial. Therefore, we performed a meta-analysis of observational studies to assess the association between various meat consumption and risk of metabolic syndrome. The PubMed and ISI Web of Science databases were searched through June 2017, and further included unpublished results from Korea National Health and Nutrition Examination Survey 2012-2015, including 8387 Korean adults. Sixteen studies were suitable for meta-analysis, which included 19,579 cases among 76,111 participants. We used a random-effects model to calculate the pooled relative risks (RR) and 95% confidence intervals (CI). The pooled RR for metabolic syndrome of the highest versus lowest category of meat intake was 1.14 (95% CI: 1.05, 1.23) for total meat, 1.33 (95% CI: 1.01, 1.74) for red meat, 1.35 (95% CI: 1.18, 1.54) for processed meat, and 0.86 (95% CI: 0.76, 0.97) for white meat. All of these associations did not differ significantly by study design and adjustment factors. Our findings indicated that total, red, and processed meat intake is positively associated with metabolic syndrome, and white meat intake is inversely associated with metabolic syndrome.


Differential response of mouse male germ-cell stages to radiation-induced specific-locus and dominant mutations.
In an attempt to provide a systematic assessment of the frequency and nature of mutations induced in successive stages of spermato- and spermiogenesis, X-irradiated male mice were re-mated at weekly intervals, and large samples of progeny, observed from birth onward, were scored and genetically tested for recessive mutations at seven specific loci and for externally recognizable dominant mutations. Productivity findings provided a rough measure of induced dominant-lethal frequencies. A qualitative assessment of specific-locus mutations (which include deletions and other rearrangements) was made on the basis of homozygosity test results, as well as from information derived from more recent complementation studies and molecular analyses. Both recessive and dominant visibles revealed clear distinctions between spermatogonia and postspermatogonial stages. In addition, differences for both of these endpoints, as well as for presumed dominant lethals, were found among various postspermatogonial stages. It may be concluded that radiation produces its maximum rates of genetic damage in germ-cell stages ranging from midpachytene spermatocytes through early spermatids, a pattern unlike any of those that have been defined for chemicals; further, the frequency peaks for radiation are lower and broader. The difference between post-stem-cell stages overall and stem-cell spermatogonia was smaller than is generally found with chemicals, not only with respect to the frequency but also the nature of mutations.


Is biology destiny after all? : three clinical conundrums: homosexuality, alcoholism, and obesity.
Recent announcements about the discovery of a biological/genetic basis for homosexuality compel psychodynamically oriented therapists to reassess once again their understanding of mind/body relations. By comparing the claims made in regard to homosexuality, where a biological basis is pronounced evidence that this orientation is natural, with the claims of alcoholism researchers, where biological differences are cited as evidence of an underlying disease, we begin to see how the metaphorical use of biology often determines the use to which research findings are put. Recent anti-diet approaches to obesity and binge eating further illustrate the limits of the dominant disease/addiction metaphors that have hitherto been used to treat these problems.


Comparative study on essential oils incorporated into an alginate-based edible coating to assure the safety and quality of fresh-cut Fuji apples.
Cinnamon, clove, and lemongrass essential oils (EOs) and their active compounds cinnamaldehyde, eugenol, and citral, respectively, were investigated for their effectiveness as antimicrobial agents in an alginate-based edible coating (EC) on fresh-cut Fuji apples. This EC also contained malic acid, N-acetyl-L-cysteine, glutathione, and calcium lactate as quality stabilizing compounds. The EC applied on apple pieces effectively maintained the physicochemical characteristics of the apple pieces for more than 30 days, decreased the respiration rate, reduced the Escherichia coli O157:H7 population by about 1.23 log CFU/g at day 0, and extended the microbiological shelf life by at least 19 days. The addition of EOs at 0.7% (vol/vol) or their active compounds at 0.5% (vol/vol) into the EC increased its antimicrobial effect, reduced the E. coli O157:H7 population by more than 4 log CFU/g, and extended the microbiological shelf life by more than 30 days. However, those concentrations of EOs affected the physicochemical characteristics of fresh-cut apples and thus limited their shelf life from 7 to 21 days. Lemongrass and cinnamon EOs (0.7%), citral (0.5%), and cinnamaldehyde (0.5%) were the most effective compounds for extending microbiological shelf life, whereas lemongrass, cinnamon, and clove EOs at 0.3% (vol/vol) best maintained the physicochemical characteristics of the product. Apple pieces with EC at day 0 and with EC with or without lemongrass EO at 0.7% at day 15 were preferred by the panelists. ECs containing natural antimicrobials and quality stabilizing compounds may be useful for extending the shelf life of fresh-cut fruits.


Health consequences of iodine deficiency.
Iodine Deficiency Disorders (IDD) are one of the biggest worldwide public health problem of today. Their effect is hidden and profoundly affects the quality of human life. Iodine deficiency occurs when the soil is poor in iodine, causing a low concentration in food products and insufficient iodine intake in the population. When iodine requirements are not met, the thyroid may no longer be able to synthesize sufficient amounts of thyroid hormone. The resulting low-level of thyroid hormones in the blood is the principal factor responsible for the series of functional and developmental abnormalities, collectively referred to as IDD. Iodine deficiency is a significant cause of mental developmental problems in children, including implications on reproductive functions and lowering of IQ levels in school-aged children. The consequence of iodine deficiency during pregnancy is impaired synthesis of thyroid hormones by the mother and the foetus. An insufficient supply of thyroid hormones to the developing brain may result in mental retardation. Brain damage and irreversible mental retardation are the most important disorders induced by iodine deficiency. Daily consumption of salt fortified with iodine is a proven effective strategy for prevention of IDD.


Methyl cinnamate protects against dextran sulfate sodium-induced colitis in mice by inhibiting the MAPK signaling pathway.
Effective and non-toxic therapeutic agents are lacking for the prevention and treatment of colitis. Previous studies found that methyl cinnamate (MC), extracted from galangal ( Alpinia officinarum Hance), has anti-inflammatory properties. However, whether MC is effective as anti-colitis therapy remains unknown. In this study, we investigate the therapeutic effects of MC on dextran sulfate sodium (DSS)-induced colitis in mice and further explore its potential mechanism of action. MC treatment relieves symptoms associated with DSS-induced colitis, including the recovery of DSS-induced weight loss, decreases the disease activity index score, and increases the colon length without toxic side effects. MC treatment protects the integrity of the intestinal barrier in mice with DSS-induced colitis and inhibits the overexpression of pro-inflammatory cytokines in vivo and in vitro. Moreover, the MAPK signaling pathway is found to be closely related to the treatment with MC of colitis. Western blot analysis show that phosphorylation of the p38 protein in colon tissues treated with MC is markedly reduced and phosphorylation levels of the p38, JNK and ERK proteins are significantly decreased in RAW 264.7 cells treated with MC, indicating that the mechanism of MC in treating DSS-induced colitis could be achieved by inhibiting the MAPK signaling pathway. Furthermore, 16S RNA sequencing analysis show that MC can improve intestinal microbial dysbiosis in mice with DSS-induced colitis. Altogether, these findings suggest that MC may be a novel therapeutic candidate with anti-colitis efficacy. Furthermore, MC treatment relieves the symptoms of colitis by inhibiting the MAPK signaling pathway and improving the intestinal microbiota.


Observations of increased levels of blood coagulation factors and other plasma proteins in cholestatic liver disease.
One group of 8 patients with primary biliary cirrhosis and one group of 7 patients with common duct stone both had generally high levels of blood coagulation factors and a wide range of other plasma proteins. In contrast, one group of 6 patients with chronic active hepatitis generally had low levels of the same coagulation factors and plasma proteins. Analyses of factor II-VII-X, plasminogen, ceruloplasmin, beta1C/1A-globulin, IgG and IgM are especially helpful in the differentiation between primary biliary cirrhosis and chronic active hepatitis. The data are interpreted as suggesting a generally increased synthesis of liver-produced proteins in cholestasis, although more specific factors may modify the degree of increase of the individual proteins.


Cell contacts in human islets of Langerhans.
The freeze-fracturing technique was applied to fresh human islets of Langerhans. With this technique, the inside of cellular membranes was revealed, and specific membrane differentiations, hitherto unknown, were observed in the plasma membrane of the endocrine cells. The specific membrane differentiations represent two types of intercellular junctions, namely the tight junction, which determines a closure of the extracellular space and the gap junction which allows molecules and ions to diffuse from one cell to another (sharing the gap junction) without leaking in the extracellular space (intercellular coupling). The presence of such junctions may be important for the secretory behavior of the cells within the islet.


Differential Tractography and Correlation Tractography Findings on Patients With Mild Traumatic Brain Injury: A Pilot Study.
Differential tractography and correlation tractography are new tractography modalities to study neuronal changes in brain diseases, but their performances in detecting neuronal injuries are yet to be investigated in patients with mild traumatic brain injury (mTBI). Here we investigated the white matter injury in mTBI patients using differential and correlation tractography. The diffusion MRI was acquired at 33 mTBI patients and 31 health controls. 7 of the mTBI patients had one-year follow-up scans, and differential tractography was used to evaluate injured fiber bundles on these 7 patients. All subjects were evaluated using digital symbol substitution test (DSST) and trail making test A (TMT-A), and the correlation tractography was performed to explore the exact pathways related to the cognitive performance. Our results showed that differential tractography revealed neuronal changes in the corpus callosum in all 7 follow-up mTBI patients with FDR between 0.007 and 0.17. Further, the correlation tractography showed that the splenium of the corpus callosum, combined with the right superior longitudinal fasciculus and right cingulum, were correlated with DSST (FDR = 0.001669) in the acute mTBI patients. The cognitive impairment findings in the acute stage and the longitudinal findings in the corpus callosum in the chronic stage of mTBI patients suggest that differential tractography and correlation tractography are valuable tools in the diagnostic and prognostic evaluation of neuronal injuries in mTBI patients.


Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat.
Under healthy conditions, the blood-brain barrier (BBB) limits the passage of solutes and cells from the blood to the CNS. During neurological diseases, BBB permeability increases dramatically and it has been hypothesized that drug carrier systems such as polymeric nanoparticles could cross the BBB and penetrate into the CNS. PEGylated polyalkylcyanoacrylate nanoparticles (long-circulating carrier) are one such system and have been investigated during experimental allergic encephalomyelitis (EAE). Brain and spinal cord concentrations of [(14)C]-radiolabelled PEGylated polyalkylcyanoacrylate nanoparticles were compared with another blood long-circulating carrier (poloxamine 908-coated polyalkylcyanoacrylate nanoparticles) and with conventional non-long-circulating polyalkylcyanoacrylate nanoparticles. The microscopic localization of fluorescent nanoparticles in the CNS was also investigated in order to further understand the mechanism by which the particles penetrate the BBB. The results demonstrate that the concentration of PEGylated nanoparticles in the CNS, especially in white matter, is greatly increased in comparison to conventional non-PEGylated nanoparticles. In addition, this increase was significantly higher in pathological situations where BBB permeability is augmented and/or macrophages have infiltrated. Passive diffusion and macrophage uptake in inflammatory lesions seems to be the mechanism underlying such particles' brain penetration. Based on their long-circulating properties in blood and on their surface characteristics that allow cell interactions, PEGylated nanoparticles penetrated into CNS to a larger extent than all the other formulations tested. Thus, PEGylated polycyanoacrylate nanoparticles are proposed here as a new brain delivery system for neuroinflammatory diseases.


[Determinants and control of energy expenditure].
Obesity is a risk factor for many diseases including cardio-vascular disease, type 2 diabetes, and certain forms of cancer, among others. Obesity results from a chronic imbalance between calorie intake and energy expenditure. Genetic factors obviously play an important role in weight gain, but only in certain environments. The principal cause of the obesity epidemic is not clear: is obesity due to excessive food intake, a dynamic reduction in energy expenditure, or an association of these two factors? However, most obese subjects gain weight because of an inaptitude to adjust energy expenditure in response to excessive food intake. In this article, we review briefly the respective role of genes and environment in the development of obesity, then describe metabolic risk factors involved. Longitudinal studies conducted in Pima Indians have demonstrated that a relative decrease in basal metabolism, weak lipid oxidation in the fasting state, reduced spontaneous physical activity, and lower sympathetic nervous system activity are risk factors for obesity. Unlike our growing knowledge of food intake regulation, little is known about the control of energy expenditure. New discoveries should provide information on obesity susceptibility genes and increase the chances of developing new anti-obesity treatments.


Effects of dietary intake of a fungal beta-D-glucan derivative on the level of DNA damage induced in primary rat hepatocytes by various carcinogens.
Water-soluble derivative of chitin-glucan complex used in our study, carboxymethyl chitin-glucan (CM-CG), enables oral administration without harmful side-effects, which can occur upon parenteral administration of the insoluble fungal beta-D-glucans. The aim of this study was to determine in ex vivo experiments the effects of dietary CM-CG on the level of DNA lesions in primary rat hepatocytes induced by various indirectly acting carcinogens. Multiorgan carcinogen benzo[a]pyrene (BaP); two hepatocarcinogens, dimethyldibenzocarbazole (diMeDBC) and N-nitrosomorpholine (NMOR); as well as a complex mixture of organic compounds adsorbed on ambient air particles (TP-S) were used for this purpose. The amount of DNA lesions was assessed using the comet assay and the micronucleus test. In addition, the mitotic indexes and the frequencies of necrotic and apoptotic cells were evaluated as well. Our results showed that the diet enriched with CM-CG (200 mg/kg of body weight) during 21 days did not induce any negative effect on DNA nor did the mitotic indexes and the frequencies of necrotic and apoptotic cells differ statistically from the controls. On the other hand, the hepatocytes isolated from CM-CG fed animals were more resistant to the action of all genotoxins used in our study [BaP (5-20 microM), diMeDBC (0.2-2 microM), NMOR (3.4-10.2 mM), TP-S (5-20 microM)]. We can conclude that in addition to the known immunopotentiating activity of beta-D-glucans, they can efficiently inhibit the genotoxicity of carcinogens requiring metabolic activation in rat heptocytes.


Effects of a nonlinear perturbation on dynamical tunneling in cold atoms.
We perform a numerical analysis of the effects of a nonlinear perturbation on the quantum dynamics of two models describing noninteracting cold atoms in a standing wave of light with a periodical modulated amplitude A(t). One model is the driven pendulum, recently considered by D.A. Steck, W.H. Oskay, and M.G. Raizen [Science 293, 274 (2001)], and the other is a variant of the well-known kicked rotator model. In absence of the nonlinear perturbation, the system is invariant under some discrete symmetries and quantum dynamical tunneling between symmetric classical islands is found. The presence of nonlinearity destroys tunneling, breaking the symmetries of the system. Finally, further consequences of nonlinearity in the kicked rotator case are considered.


[Perinatal variables from newborns of Aymara mothers suggest a genetic adaptation to high altitude].
Studies performed in Andean populations living in high altitude, indicate that the reduced availability of oxygen could be associated to both a fetal growth retardation and a lower birth weight. These variables are predictive of morbidity and mortality during the first year of life. To study perinatal variables of newborns of mothers living at contrasting altitudinal levels, harboring different degrees of Aymara ancestry. Review of medical records of 5,295 women whose deliveries occurred between February 2004 and August 2010. Information was obtained on place of residence, grouped into two categories: coast (150 to 3,000 m) and high plateau (3,000 to 4,300 m), ancestry was estimated using number of Aymara surnames that were homologated to percentages of Amerindian admixture, gestational age, birth weight, height, head circumference and obstetric variables. Gestational age showed a tendency to increase and birth weight, height and head circumference to decrease with altitude of residence. Only weight reached statistical significance. Women with Aymara ancestry gave birth to children with a significantly higher gestational age, weight and cranial circumference. Altitude of residence is related to a decrease in perinatal variables that proved to be less pronounced in newborns of mothers with a higher degree of Aymara ancestry. RESULTS suggest a genetic adaptation to hypoxia that could be related to candidate genes linked to the capture, transport or utilization of oxygen.


Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND.
Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70 % of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers.


A poplar tree proteinase inhibitor-like gene promoter is responsive to wounding in transgenic tobacco.
Wounding of poplar trees leads to the accumulation of several mRNA species that encode proteins with putative defensive function. One class of wound-induced poplar RNA (win3) has amino acid sequence similarity to Kunitz-type trypsin inhibitors. Northern blots and cDNA sequencing show that several win3 mRNAs accumulate in the uninjured leaves of wounded trees. We report further characterization of the win3 family including sequence comparisons, gene family organization, and the identification of one win3 member that is transcriptionally activated in response to mechanical wounding. We also show that 1.5 kb of 5'-flanking sequence of one win3 member (win3.12) is sufficient to confer wound-regulated expression of a beta-D-glucuronidase (GUS) reporter gene in transgenic tobacco. Annual herbaceous plants such as tobacco can thus be used to study the expression of genes from a perennial woody angiosperm.


Effect of intracanal medicaments on push-out bond strength of Smart-Seal system.
To evaluate the effects of calcium hydroxide (CH), triple and double antibiotic pastes (DAPs) on the bond strength of Smart-Seal obturation, C-points with Endosequence Bio-ceramic (BC) sealer to the root canal dentin. Sixty-four freshly extracted single-rooted human mandibular premolars were de-coronated and prepared using rotary Pro-taper system with full sequence till F3. The specimens were randomly divided into a control group (without intracanal dressing) and 3 experimental groups that received an intracanal dressing with either CH, DAP, or triple antibiotic paste (TAP) (n = 16). The intracanal dressing was removed after 3 weeks by rinsing with 10 mL 17% ethylenediaminetetraacetic acid, followed by 10 mL 3% sodium hypochlorite. The root canals were then obturated with C-points and Endosequence BC sealer. A push-out test was used to measure the bond strength between the root canal dentin and the obturating system. The data were analyzed using two-way analysis of variance and Tukey post-hoc test. The push-out bond strength values were significantly affected by the intracanal medicaments (P < 0.001), but not by the root canal thirds (P > 0.05). In the middle and apical third, the bond strength of the TAP group was higher than those of the CH and DAP groups (P < 0.05). The DAP and CH did not affect the bond strength of the novel hydrophilic obutrating system. TAP improved the bond strength of Smart-Seal system in the middle and apical thirds.


Differential interaction of beta 1- and beta 3-adrenergic receptors with Gi in rat adipocytes.
The interaction of beta 1- and beta 3-adrenergic receptors and G(i) proteins was examined in rat adipocytes. In intact adipocytes, cyclic AMP accumulation stimulated by the beta 3-selective agonist, BRL 37344 (BRL), was potentiated by pertussis toxin (PTX), as was the beta 1-sensitive component of isoproterenol (ISO)-stimulated cyclic AMP accumulation. These data suggest that beta 1 and beta 3-receptors interact with both Gs and G(i) in intact adipocytes. Further analysis of the activation of adenylyl cyclase by the beta-receptor subtypes was performed in adipocyte membranes in which the activity of G(i) was manipulated by both GTP and PTX. Unlike cyclic AMP accumulation in cells, the activation of membrane adenylyl cyclase by ISO could be clearly resolved into components mediated by beta 1-(high affinity) or beta 3-(low affinity) receptors. The beta 3-receptor-mediated activity was dramatically reduced at 0.1 mM GTP compared to 0.1 microM GTP, but the activity mediated by beta 3-receptors was significantly reduced at concentrations of GTP in which G(i) proteins are active. Adenylyl cyclase activity stimulated by BRL was also inhibited at high concentrations of GTP. PTX abolished the inhibition of beta 3-receptor-stimulated activity by high GTP concentrations. This is the first study to indicate that G(i) proteins can limit beta 3- but not beta 1-stimulated adenylyl cyclase activity and are consistent with the hypothesis that beta 3-receptors interact with both Gs and G(i), whereas beta 1-receptors couple predominantly to Gs.


Cultivating across "pockets of excellence": challenges to sustaining efforts to improve osteoporosis care.
We conducted in-depth, semi-structured interviews with clinicians involved in bone health care to understand the challenges of implementing and sustaining bone health care interventions. Participants identified individual- and system-level challenges to care delivery, implementation, and sustainment. We discuss opportunities to address challenges through a commitment to relationship- and infrastructure-building support. Osteoporosis and fracture-related sequalae exact significant individual and societal costs; however, identification and treatment of at-risk patients are troublingly low, especially among men. The purpose of this study was to identify challenges to implementing and sustaining bone health care delivery interventions in the Veterans Health Administration. We conducted interviews with endocrinologists, pharmacists, primary care physicians, rheumatologists, and orthopedic surgeons involved in bone health care (n = 20). Interviews were audio-recorded and transcribed verbatim. To determine thematic domains, we engaged in an iterative, qualitative content analysis of the transcripts. Participants reported multiple barriers to delivering bone health care and to sustaining the initiatives designed to address delivery challenges. Challenges of bone health care delivery existed at both the individual level-a lack of patient and clinician awareness and competing clinical demands-and the system level-multiple points of entry to bone health care, a dispersion of patient management, and guideline variability. To address the challenges, participants developed initiatives targeting the identification of at-risk patients, clinician education, increasing communication, and care coordination. Sustaining initiatives, however, was challenged by staff turnover and the inability to achieve and maintain priority status for bone health care. The multiple, multi-level barriers to bone health care affect both care delivery processes and sustainment of initiatives to improve those processes. Barriers to care delivery, while tempered by intervention, are entangled and persist alongside sustainment challenges. These challenges require relationship- and infrastructure-building support.


Persistently biased T-cell receptor repertoires in HIV-1-infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication.
In most HIV-1-infected patients, highly active antiretroviral therapy (HAART) reduces plasma viral load to <50 copies/mL and increases CD4+ T-cell number and function. However, it is still unclear whether alterations of T-cell receptor (TCR) beta-chain variable region (BV) repertoire, tightly related to disease progression, can be fully recovered by long-term treatment with HAART. This study analyzed the evolution of both T-cell subset composition and TCRBV perturbations in chronically HIV-1-infected patients with moderate immunodeficiency during 36 months of HAART. Despite persistently suppressed HIV replication, the rate of CD4+ T-cell repopulation, after an initial burst, progressively declined throughout the study period, resulting in a mean CD4+ T-cell count at the end of follow-up that was still significantly lower in HIV patients than in HIV-seronegative controls. This was seen in association with an incomplete restitution of both CD4 and CD8 TCRBV repertoire disruptions and was also demonstrated by the appearance of new TCRBV oligoclonal expansions occurring during HAART. In conclusion, these data indicate that 3 years of fully suppressive HAART may be not adequate to normalize CD4 counts and TCRBV repertoires in patients starting HAART with moderately advanced disease.


Severity and outcome associated with human coronavirus OC43 infections among children.
Human coronaviruses are known causes of the common cold. Subtype OC43 (HCoV-OC43) is the more prevalent human coronavirus in several parts of the world. Recent studies have suggested these viruses can cause severe lower respiratory tract illnesses in children. We sought to determine the epidemiology, clinical characteristics, outcomes and severity of illness associated with HCoV-OC43 infections in a pediatric population. We retrospectively identified patients with positive HCoV-OC43 respiratory specimens between December 2009 and December 2010 in a pediatric hospital in Montreal. Each case was compared with 2 controls (tested negative for HCoV-OC43). Clinical characteristics, underlying conditions, outcomes and disease severity were reviewed for both groups. Risk factors and independent predictors of disease severity were also assessed. During the study period, 68 patients were identified as infected with HCoV-OC43 (1.8% of specimens tested, 4.2% of all respiratory viruses identified by reverse transcription polymerase chain reaction). The majority (77%) occurred in November 2010. Chief symptoms of HCoV-OC43 infection were fever (in 78% of cases), cough (67%) and upper respiratory tract infection symptoms (57%). HCoV-OC43 infection was not more frequent in children with preexisting conditions. Coinfection with other respiratory viruses was associated with lower respiratory tract infections in HCoV-OC43-infected cases, but did not lead to increased rates of hospitalization, admission to intensive care unit or death. In our population, HCoV-OC43 infections generally caused upper respiratory tract infection, but can be associated with lower respiratory tract infection especially in those coinfected with other respiratory viruses.