Grower Analysis of Organic Matter Amendments in California Orchards.
Organic matter amendments supply crop nutrients and enhance soil health, yet information specific to orchards is lacking. A survey was conducted to analyze use of these materials by California almond [ (Mill.) D.A. Webb] growers. Significant differences were observed for benefits, concerns, and accessibility to manure and green waste sources and between users and nonusers. Use patterns were significantly influenced by heavy and light users, farm size, and geographic region. Enhanced soil biology was the main benefit attributed to organic matter amendments by both users and nonusers. Nonusers showed greater concern for food safety compared to users, and all growers reported greater concern for food safety from manure. The greatest adoption of organic matter amendments occurred on small farms (≤170 ha) located in the north San Joaquin Valley in California. Greater accessibility to manure correlated with presence of dairy farms. Poorer accessibility ratings by nonusers suggest access is a barrier to adoption, as opposed to nonusers having an undesirable view of the practice. Common management included applying organic matter amendments during tree dormancy from manure sources in composted forms with no-till. Heavy users on small farms exhibited the greatest year-to-year consistency and were more flexible with selection of sources and diverse in application methods. Large farms (>170 ha) were less likely to use organic matter amendments every year and less likely to apply them on all their farm area. This study identifies a number of strategies to fill knowledge gaps, increase practice awareness, and overcome barriers to adoption.


Chronic obstructive pulmonary disease. A possible correlation between platelet aggregation tests and respiratory indexes. ECOB Group.
It has been suggested that thrombotic events occurring in patients with chronic obstructive pulmonary disease could be partially due to abnormalities in blood coagulation and fibrinolysis, as well as to changes in platelet function. In the present study in vitro platelet aggregation, in addition to clotting activity, has been studied in 20 patients with chronic obstructive pulmonary disease and different degrees of alteration of blood gas analysis. The results obtained suggest that the presence of a condition of platelet hypoaggregability characterizes patients with marked hypercapnia and/or hypoxemia, whereas the improvement of respiratory indexes is followed by a trend to normalization, or, more often, to an increase of platelet activity.


The incidence of HLA-DQ2/DQ8 in Turkish children with celiac disease and a comparison of the geographical distribution of HLA-DQ.
Celiac disease (CD) is an auto-immune enteropathy that occurs in genetically pre-disposed people as a result of the consumption of gluten-containing foods. To identify the incidence of HLA-DQ2 and HLA-DQ8 observed in children with CD. In this study, we focused on children ranging in age from 2 to 18 years and diagnosed with celiac disease. In our patients diagnosed with CD, in addition to tissue transglutaminase antibodies (anti-tTG), we also evaluated HLA-DQ2 B1 and HLA-DQ8 B1 alleles using the method of polymerase chain reaction (PCR)/sequence-specific oligonucleotide probes (Luminex®). The detection of 0201/0202 for HLA-DQ2 allele and 0302 for HLA-DQ8 allele was accepted as a positive result. The mean age of our patients with celiac disease was 7.42 ±3.18 years, and the female/male ratio was 1.5/1. Seventy-six percent of our patients were HLA-DQ2 and/or HLA-DQ8 positive, 67% were HLA-DQ2 positive, and 25% were HLA-DQ8 positive. Nevertheless, 24% of them were HLA-DQ2 and HLA-DQ8 negative. The incidence of HLA-DQ2 in the control group was 18.8% with a significant difference compared to the HLA-DQ2 incidence in the patient group (67%) (p < 0.05). Similarly the HLA-DQ8 incidence in the control group (5.7%) was significantly lower than the incidence in the patient group (25%) (p < 0.05). The incidence of the patients diagnosed with CD, who are HLA-DQ2 and HLA-DQ8 negative, varies among different populations.


Integrating pharmacogenomics into precision pain management.
Studies suggest wide heterogeneity in pain management response. Improved methods of pain pharmacotherapy are urgently needed to improve clinical response and safety profile of analgesics. The study or application of how genetics influence response to medications is called pharmacogenomics (PGx). PGx testing is a tool that may support more precise selection and dosing of pain medicines. PGx guidelines exist for drug-gene interactions with high levels of evidence and can be applied in clinical practice for more precise care in patients with cancer. The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a publicly funded international consortium of experts who curate published PGx data and create peer-reviewed guidelines on how to translate PGx results into actionable prescribing decisions. Given the immense need to improve pain management, it is important to increase awareness and consider application of CPIC guidelines to pain management strategies. This commentary concisely describes how PGx can be used to aid in more precise applications of pain pharmacotherapy based on the CPIC guidelines.


A cyclooxygenase-2 inhibitor ameliorates behavioral impairments induced by striatal administration of epidermal growth factor.
Consistent with the hypothesis that neuroinflammatory processes contribute to the neuropathology of schizophrenia, the protein levels of epidermal growth factor (EGF) and its receptor ErbB1 are abnormal in patients with schizophrenia. To evaluate neuropathological significance of this abnormality, we established an animal model for behavioral deficits by administering EGF into the striatum and evaluated the effects of cyclooxygenase-2 (Cox-2) inhibitor celecoxib. Intracranial infusion of EGF into the striatum of adult male rats activated ErbB1 and induced neurobehavioral impairments observed in several schizophrenia models. Unilateral EGF infusion to the striatum lowered prepulse inhibition (PPI) in a dose-dependent manner and impaired latent learning of active shock avoidance without affecting basal learning ability. Bilateral EGF infusion similarly affected PPI. In contrast, EGF infusion to the nucleus accumbens did not induce a behavioral deficit. Intrastriatal EGF infusion also increased Cox-2 expression, elevated tyrosine hydroxylase activity, and upregulated the levels of dopamine and its metabolites. Subchronic administration of celecoxib (10 mg/kg, p.o.) ameliorated the abnormalities in PPI and latent learning as well as normalized dopamine metabolism. We conclude that this EGF-triggered neuroinflammatory process is mediated in part by Cox-2 activity and perturbs dopamine metabolism to generate neurobehavioral abnormalities.


Twenty-four-hour rhythms of serum ACTH, prolactin, growth hormone, and thyroid-stimulating hormone, and of median-eminence norepinephrine, dopamine, and serotonin, in rats injected with Freund's adjuvant.
The effect of Freund's adjuvant injection on 24-h variation of circulating ACTH, prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH) levels, and of norepinephrine (NE) content, and dopamine (DA) and serotonin (5HT) turnover in median eminence, was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of 6-10 animals received Freund's complete adjuvant or its vehicle at 1100 h 3 days before sacrifice and were killed by decapitation at six different time intervals throughout a 24-h cycle. In rats injected with adjuvant's vehicle, serum ACTH and prolactin exhibited peak values around the light-dark transition (p < 0.0001 and < 0.04, respectively), while the maximum in TSH was found in the late afternoon (p < 0.0001, one-way ANOVA). GH levels did not vary on a 24-h basis. In Freund's adjuvant-injected rats, 24-h variations of TSH levels became blunted, while 24-h variations of prolactin and ACTH persisted. Freund's adjuvant augmented serum ACTH and prolactin levels, and decreased GH and TSH levels (p < 0.0007, factorial ANOVA). Median-eminence NE content, and turnover of DA, assessed by measuring dihydroxyphenylacetic acid, DOPAC/DA ratio, and of 5HT, assessed by measuring 5-hydroxyindoleacetic acid, HIAA/5HT ratio, varied on a 24-h basis in rats receiving adjuvant's vehicle (p < 0.02). Median-eminence NE content attained its maximum at 1600-2000 h, while maxima in DOPA/DA and HIAA/5HT ratios occurred at 0400 h. Injection with Freund's adjuvant reduced the amplitude of the daily variation of NE content, shifted the maximum of DOPAC/DA ratio toward the light-dark transition, and blunted the daily variation in HIAA/5HT ratio in median eminence. The administration at 1200 of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) restored the augmented ACTH and prolactin levels (p < 0.0001, factorial ANOVA) and depressed GH and TSH levels (p < 0.02) found in Freund's adjuvant-injected rats. Cyclosporine was also effective in restoring 24-h rhythmicity of serum ACTH and TSH, but not of prolactin, levels. Cyclosporine did not modify the effect of Freund's adjuvant on time-of-day changes of median-eminence NE content, but it was effective in counteracting the changes of DA and 5HT turnover found after immunization. The results are compatible with a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on ACTH, GH, prolactin, and TSH release, which is partially sensitive to immunosuppression by cyclosporine.


Time modulated prefrontal and parietal activity during the maintenance of integrated information as revealed by magnetoencephalography.
Using magnetoencephalography, we investigated the spatiotemporal patterns of brain magnetic activity responsible for maintaining verbal and spatial information in either an integrated or an unintegrated fashion. Considering time dimension, we noted a greater activation of a fronto-parietal network in early latencies during the maintenance of integrated information, and a different pattern during the maintenance of unintegrated material, showing a greater activation in a fronto-posterior network in late latencies. The greater activation found in certain areas which are traditionally reported as being engaged in spatial working memory (i.e. superior frontal gyri, dorsolateral prefrontal cortex, superior and inferior parietal lobes) when subjects maintained integrated information could be explained by a greater weight of the spatial dimension. It is as if words somehow acquired a spatial attribute, thus exerting a greater load in a neural network specialized in spatial working memory. Alternatively, and not mutually exclusive, we also propose that during the maintenance of integrated information the allocation of cognitive resources is less interfering than during the maintenance of unintegrated information, making it easier.


V beta 8+CD4-CD8- subpopulation induced by staphylococcal enterotoxin B.
Injection of staphylococcal enterotoxin B (SEB) into BALB/c mice induced the depletion of V beta 8+ T-cells which were either V beta 8+CD4+ or V beta 8+CD8+ cells. The CD8 molecule on V beta 8+CD8+ cells was found to decrease at 72 h after SEB treatment while the V beta 8 molecule on V beta 8+ cells or CD4 molecule on V beta 8+CD4+ cells was not affected. Furthermore, a subpopulation of V beta 8+CD4-CD8- T-cells was also induced after SEB-priming. This subpopulation can be found in spleen or lymph nodes. It was small in size and constituted the major part of V beta 8+ cells in lymph nodes at 72 h after SEB-priming. Some of the V beta 8+CD4-CD8- T-cells might be autoreactive because they could be stimulated to proliferative by syngenic mitomycin C-treated splenocytes.


Cell sheet technology for heart failure.
Heart failure is a life threatening disorder in worldwide and many papers reported about myocardial regeneration through surgical method induced by LVAD, cellular cardiomyoplasty (cell injection), tissue cardiomyoplasty (bioengineered cardiac graft implantation), in situ engineering (scaffold implantation), and LV restrictive devices. Some of these innovated technologies have been introduced to clinical settings. This review article provides summary about recent basical and clinical advances about myocardial regeneration induced by bioengineered cardiac tissue.


[Nursing and case management].
This study presents case management as a care delivery model which is used in a variety of settings in the United States health care system. It basically designates a specific professional or health care team which is responsible for the care of an individual patient in the whole clinical process by coordinating care throughout services and institutions in the system. In nursing, the model has been accepted to increase the nurse's commitment in the standardization of practice. Central concepts include analysis, clinical decision-making and resolution of problems.


Lagrangian refined Kolmogorov similarity hypothesis for gradient time evolution and correlation in turbulent flows.
We study time evolution of velocity and pressure gradients in isotropic turbulence by quantifying their autocorrelation functions and decorrelation time scales. The Lagrangian analysis uses data in a public database generated by direct numerical simulation at a Reynolds number Re{lambda} approximately 433. It is confirmed that when averaging over the entire domain, correlation functions decay on time scales on the order of the global Kolmogorov turnover time scale. However, when performing the analysis in different subregions of the flow, turbulence intermittency leads to large spatial variability in the decay time scales. Remarkably, excellent collapse of the autocorrelation functions is recovered when using a locally defined Kolmogorov time scale. This provides new evidence for the validity of Kolmogorov's refined similarity hypothesis, but from a Lagrangian viewpoint that provides a natural frame to describe the dynamics of turbulence.


Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer.
MET inhibition is effective in some patients with MET-amplified esophagogastric cancer (EGC), but understanding acquired and de novo resistance mechanisms will be critical to improving therapy. We identified KRAS mutation as a novel cause of acquired resistance in a patient after a 2-year response to a MET inhibitor. We also observed that 40% to 50% of patients with MET-amplified EGC harbor coamplification of HER2 and/or EGFR concurrently in the same tumor cells, which can drive de novo resistance. One patient with concurrent MET and HER2 amplification was refractory to HER2 blockade, but responded to combined MET/HER2 inhibition. We also found striking heterogeneity in MET amplification between distinct metastatic lesions and primary tumors in individual patients with EGC. In these patients, MET inhibition led to mixed responses and disease progression through outgrowth of non-MET-amplified clones, which could be monitored in circulating tumor DNA. Thus, receptor coamplification and molecular heterogeneity may be key drivers of clinical resistance in MET-amplified EGC. Coamplification of driver oncogenes occurs frequently in EGC and can drive therapeutic resistance, supporting a role for comprehensive molecular analysis prior to targeted therapy. EGCs can also exhibit extensive heterogeneity in gene amplification between distinct tumor lesions within the same patient, suggesting that molecular profiling of a single-lesion biopsy may be insufficient to guide targeted therapy selection.


Genetically altered expression of spermidine/spermine N1-acetyltransferase affects fat metabolism in mice via acetyl-CoA.
The acetylating enzyme, spermidine/spermine N1-acetyltransferase, participates in polyamine homeostasis by regulating polyamine export and catabolism. Previously, we reported that overexpression of the enzyme in cultured tumor cells and mice activates metabolic flux through the polyamine pathway and depletes the N1-acetyltransferase coenzyme and fatty acid precursor, acetyl-CoA. Here, we investigate this possibility in spermidine/spermine N1-acetyltransferase transgenic mice in which the enzyme is systemically overexpressed and in spermidine/spermine N1-acetyltransferase knock-out mice. Tissues of the former were characterized by increased N1-acetyltransferase activity, a marked elevation in tissue and urinary acetylated polyamines, a compensatory increase in polyamine biosynthetic enzyme activity, and an increase in metabolic flux through the polyamine pathway. These polyamine effects were accompanied by a decrease in white adipose acetyl- and malonyl-CoA pools, a major (20-fold) increase in glucose and palmitate oxidation, and a distinctly lean phenotype. In SSAT-ko mice, the opposite relationship between polyamine and fat metabolism was observed. In the absence of N1-acetylation of polyamines, there was a shift in urinary and tissue polyamines indicative of a decline in metabolic flux. This was accompanied by an increase in white adipose acetyl- and malonyl-CoA pools, a decrease in adipose palmitate and glucose oxidation, and an accumulation of body fat. The latter was further exaggerated under a high fat diet, where knock-out mice gained twice as much weight as wild-type mice. A model is proposed whereby the expression status of spermidine/spermine N1-acetyltransferase alters body fat accumulation by metabolically modulating tissue acetyl- and malonyl-CoA levels, thereby influencing fatty acid biosynthesis and oxidation.


Four new furostanol saponins from the rhizomes and roots of Smilax scobinicaulis and their cytotoxicity.
Four new furostanol saponins 1-4, along with two known furostanol saponins 5 and 6 and one known spirostanol saponin 7 were isolated from the rhizomes and roots of Smilax scobinicaulis. The structures of the new saponins were elucidated as 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one-3-O-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside (1), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-22-methoxyl-6-one (2), 26-O-β-D-glucopyranoside-3β,26-dihydroxy-(25R)-5α-furostan-20(22)-en-6-one (3), 26-O-β-D-glucopyranoside-3β,23,26-trihydroxy-(23R, 25R)-5α-furostan-20(22)-en-6-one (4) on the basis of spectroscopic analysis. The isolated saponins were evaluated for cytotoxic activity against two human cancer cell lines including Hela (cervical carcinoma) and SMMC-7221 (hepatocellular carcinoma). Compounds 1 and 7 demonstrated cytotoxicity against the tested cell lines.


Increased exposure to alcohol and cannabis education and changes in use patterns.
The introduction of new alcohol and cannabis education programs in Ontario schools was associated with significant increases in reported exposure to alcohol and cannabis education. Significant increases were reported for both sexes, all grade levels, and geographic areas. These were associated with decreases in proportions of drinkers, especially among younger students. Little effect was seen on heavy drinking. The evidence also suggests that reported increased exposure to cannabis education was not associated with reduced cannabis use. The challenge remains to develop alcohol education programs which can reduce heavy drinking and to develop effective cannabis education programs.


Changes in quality of care and costs induced by implementation of a diabetes program in a social security entity of Argentina.
To measure the impact of a diabetes and cardiovascular risk factors program implemented in a social security institution upon short- and long-term clinical/metabolic outcomes and costs of care. Observational longitudinal cohort analysis of clinical/metabolic data and resource use of 300 adult male and female program participants with diabetes before (baseline) and 1 and 3 years after implementation of the program. Data were obtained from clinical records (Qualidiab) and the administration's database. The implementation of the program in "real world" conditions resulted in an immediate and sustainable improvement of the quality of care provided to people with diabetes incorporated therein. We also recorded a more appropriate oral therapy prescription for hyperglycemia and cardiovascular risk factors (CVRFs), as well as a decrease of events related to chronic complications. This improvement was associated with an increased use of diagnostic and therapeutic resources, particularly those related to pharmacy prescriptions, not specifically used for the control of hyperglycemia and other CVRFs. The implementation of a diabetes program in real-world conditions results in a significant short- and long-term improvement of the quality of care provided to people with diabetes and other CVRFs, but simultaneously increased the use of resources and the cost of diagnostic and therapeutic practices. Since controlled studies have shown improvement in quality of care without increasing costs, our results suggest the need to include management-control strategies in these programs for appropriate medical and administrative feedback to ensure the simultaneous improvement of clinical outcomes and optimization of the use of resources.


Effect of prostaglandins on chloropromazine induced catalepsy in mice.
The effect of prostaglandins (PGs) F1 alpha, F2 alpha, E2, D2, A1, B1 and I2 administered intracerebroventricularly (i.c.v.) in mice in a dose of 1 microgram on catalepsy induced by chloropromazine (2.5 mg/kg i.p.) was examined. It was demonstrated that only PGF2 alpha reduced significantly the chloropromazine induced catalepsy, while PGI2 intensified it. The other examined PGs were without any effect on chlorpromazine catalepsy. The results show the modifying role of some PGs on chloropromazine effects on central dopaminergic receptors in mice.


The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.
For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.


Malignant giant cell tumor of soft parts in a mare.
Two subcutaneous masses were removed from the elbow of a mare. Histologically they were composed of islands of polygonal to plump spindlelioid cells with large nuclei, coarsely stippled chromatin, and eosinophilic cytoplasm. Findings were diagnostic for a malignant giant cell tumor of soft parts, a rare tumor with a fair prognosis.


Current readings: Percutaneous ablation for pulmonary metastatic disease.
Percutaneous image-guided ablation is a technique for maintaining local control of metastatic lung lesions that may, in selected patients, confer a survival benefit over no treatment or systemic therapy alone. Although the currently accepted treatment for oligometastatic pulmonary disease is surgical resection, the existing body of literature, including the recent investigations reviewed within this article, supports a role for percutaneous ablation as an important and relatively safe therapeutic option for nonsurgical and in carefully selected surgical patients, conferring survival benefits competitive with surgical metastasectomy. Continued clinical investigations are needed to further understand the nuances of thermal technologies and applications to treat lung primary and secondary pulmonary malignancy, directly compare available therapeutic options and further define the role of percutaneous image-guided ablation in the treatment of pulmonary metastatic disease.


Impact of climate conditions on hospital admissions for subcategories of cardiovascular diseases.
The aim of this study has been to examine the association between climate conditions (CC) and hospital admissions for the subcategories of cardiovascular diseases (CVD), according to patients' age. From January 2010 through December 2011, the daily number of hospital admissions for angina pectoris (AP), essential hypertension (EH), acute myocardial infarction (AMI) and ischemic heart diseases (IHD) for adults (19-64 years old) and the elderly (≥ 65 years old), as well as for the CC (N = 728 days) was collected for multivariate Poisson regression analysis, confounding with season and weekends. The results were expressed by using the relative risk with the corresponding 95% confidence interval. The risk for the AMI among the adults and the elderly is significantly higher for 41.8% and 38.9%, respectively on the days with lower ambient temperature and lesser for 32.7% and 29.8%, respectively on the days with lower air pressure values. The risk for the IHD among the elderly is significantly higher on the days with lower ambient temperature and lower relative humidity for 50.6% and 37.4%, respectively. Our findings explain how the CC and subcategories of CVD are associated, which could be used for adequate public awareness of the risk for hospitalization due to climate conditions. Med Pr 2017;68(2):189-197.


Pharmacogenetics in breast cancer: focus on hormone therapy, taxanes, trastuzumab and bevacizumab.
Breast cancer is the most common female cancer, with more than one million new patients diagnosed annually worldwide. The great heterogeneity, in terms of prognosis and outcome, within patients with the same clinical and pathological characteristics may limit the potential for personalized therapy. Most of the cytotoxic agents and new targeted agents have a narrow therapeutic index and the administration of an equal dose may result in a wide range of toxicities as well as to different antitumor efficacy. Inter-subject variability in drug toxicity and response is common during treatment, so that individualization of treatments is an important issue. Pharmacogenetics is the study of how inter-individual variations in the DNA sequence of specific genes may affect drug response and toxicity. This article highlights the clinical use of determination of polymorphisms of important human drug-metabolizing cytochrome P450s, ABCB1, IgG fragment C receptors and vascular endothelial growth factor, which are responsible of the large inter-individual variability in drug metabolism and clearance of the agents commonly used in breast cancer treatment, such as tamoxifen, aromatase inhibitors, taxanes, trastuzumab and bevacizumab.


Isolation of an Eleven-Atom Polydentate Carbon-Chain Chelate Obtained by Cycloaddition of a Cyclic Osmium Carbyne with an Alkyne.
Carbon ligands have long played an important role in organometallic chemistry. However, previous examples of all-carbon chelating ligands are limited. Herein, we present a novel complex with an eleven-atom carbon chain as a polydentate chelating ligand. This species was formed by the [2+2+2] cycloaddition reaction of two equivalents of an alkyne with an osmapentalyne that contains the smallest carbyne bond angle (127.9°) ever observed. Density functional calculations revealed that electron-donating groups play a key role in the stabilization of this polydentate carbon-chain chelate. This process is also the first [2+2+2] cycloaddition reaction of an alkyne with a late-transition-metal carbyne complex. This study not only enriches the chemistry of polydentate carbon-chain chelates, but also deepens our understanding of the chelating ability of carbon ligands.


NF-κB Signaling Pathway Inhibitors as Anticancer Drug Candidates.
Cancer incidence represents an important public health problem worldwide. Nuclear factor kappa B (NF- κB) transcription factor plays a pivotal role in the regulation of genes that control various responses in eukaryotic cells, including proliferation and survival, cytoskeletal remodeling, cellular adhesion and apoptosis. Extensive studies have demonstrated the contribution of NF-κB transcription in the promotion and progression of several hematological malignancies and solid tumors, in which NF-κB constitutive activation and/or overexpression are common clinical features. Moreover, triggering the NF-κB pathway is already considered one of the important mechanisms of resistance development to chemotherapy and radiotherapy, indicating that the inhibition of this signaling cascade is a promising approach to enhancing efficacy and preventing acquired resistance in cancer treatment. In this review, research efforts dedicated to the identification of novel NF-κB signaling pathway inhibitors as promising anticancer drug candidates are described.


H' Shaped Bilobate Placental Partition: A Rare Placenta Variation.
Anomalies of placental growth with respect to its shape have been associated with adverse pregnancy outcomes. A very rare form of 'H' bilobate placental partition was observed in a 31-year-old woman presenting at 24 weeks of gestation. This observation was made during a routine obstetrics scan. Sonographic features showed that it was a non-fibroid partition. The placenta featured anterior and posterior portions separated by a large middle, vertical portion. The placenta was antero-posterior semi-circumferential in shape, measuring approximately 16.70 cm in length and 12.48 cm at shorter chorionic plate (minor axis). The middle, vertical part of the placenta partitioned the uterine cavity into two, creating the impression of two separate gestational sacs. The fetus was located in one of these. The patient was eventually delivered through caesarean section at gestational age (GA) of 36 weeks 6 days. The baby had a low birth weight of 1.70 kg. The early detection of this placental anomaly underlines the importance of ultrasonography in obstetrics.


Topological vulnerability of power grids to disasters: Bounds, adversarial attacks and reinforcement.
Natural disasters like hurricanes, floods or earthquakes can damage power grid devices and create cascading blackouts and islands. The nature of failure propagation and extent of damage, among other factors, is dependent on the structural features of the grid, that are distinct from that of random networks. This paper analyzes the structural vulnerability of real power grids to impending disasters and presents intuitive graphical metrics to quantify the extent of topological damage. We develop two improved graph eigen-value based bounds on the grid vulnerability. Further we study adversarial attacks aimed at weakening the grid's structural robustness and present three combinatorial algorithms to determine the optimal topological attack. Simulations on power grid networks and comparison with existing work show the improvements of the proposed measures and attack schemes.


Endometrial Cancer Presentation and Outcomes Based on Mismatch Repair Protein Expression From a Population-Based Study.
There is uncertainty about the prognostic significance of mismatch repair (MMR) deficiency in endometrial cancer. The objective was to evaluate clinical characteristics and outcomes of endometrial cancers based on MMR status within a population-based study. This was a retrospective population-based cohort study of all endometrial cancer cases from the Vancouver Coastal Health Authority region, evaluated for 4 MMR proteins using immunohistochemistry from 2012 to 2015. Patients were classified as MMR deficient (dMMR, any MMR protein absent) or MMR proficient (pMMR), Demographics, tumor characteristics, recurrences, and survival rates were compared according to MMR status. There were 892 patients, with 650 pMMR (72.5%) and 242 dMMR tumors. The dMMR group had more endometrioid tumors (87.6% vs 74.0%, P < 0.001), lymphovascular space invasion (43.8% vs 30.8%, P = 0.001), and dedifferentiation (5.9% vs 1.5%, P < 0.001), but fewer grade 1 tumors compared with the pMMR group (31.8% vs 40.8%, P < 0.001). Median progression-free survival and overall survival have not been reached. After a median follow-up of 31 months (1-99 months), there was no difference in progression or recurrence rates between pMMR and dMMR tumors (19.5% vs 16.5%; P = 0.31). However, among those with nonendometrioid tumors, recurrence and mortality rates were significantly higher for pMMR than dMMR tumors (42.0% vs 10.0%, P = 0.001, and 36.1% vs 13.1%, P = 0.01, respectively), despite similar stage and lymphovascular space invasion distributions. In this population-based study, there were no significant differences in recurrence or survival outcomes according to MMR status in endometrial cancer. However, among those with nonendometrioid tumors, there were lower recurrence and mortality rates associated with MMR-deficient compared with MMR-proficient tumors.


Insertion of an imprinted insulator into the IgH locus reveals developmentally regulated, transcription-dependent control of V(D)J recombination.
The assembly of antigen receptor loci requires a developmentally regulated and lineage-specific recombination between variable (V), diversity (D), and joining (J) segments through V(D)J recombination. The process is regulated by accessibility control elements, including promoters, insulators, and enhancers. The IgH locus undergoes two recombination steps, D-J(H) and then V(H)-DJ(H), but it is unclear how the availability of the DJ(H) substrate could influence the subsequent V(H)-DJ(H) recombination step. The Eμ enhancer plays a critical role in V(D)J recombination and controls a set of sense and antisense transcripts. We epigenetically perturbed the early events at the IgH locus by inserting the imprinting control region (ICR) of the Igf2/H19 locus or a transcriptional insulator devoid of the imprinting function upstream of the Eμ enhancer. The insertions recapitulated the main epigenetic features of their endogenous counterparts, including differential DNA methylation and binding of CTCF/cohesins. Whereas the D-J(H) recombination step was unaffected, both the insulator insertions led to a severe impairment of V(H)-DJ(H) recombination. Strikingly, the inhibition of V(H)-DJ(H) recombination correlated consistently with a strong reduction of DJ(H) transcription and incomplete demethylation. Thus, developmentally regulated transcription following D-J(H) recombination emerges as an important mechanism through which the Eμ enhancer controls V(H)-DJ(H) recombination.


Plant preference for ammonium versus nitrate: a neglected determinant of ecosystem functioning?
Although nitrogen (N) availability is a major determinant of ecosystem properties, little is known about the ecological importance of plants' preference for ammonium versus nitrate (β) for ecosystem functioning and the structure of communities. We modeled this preference for two contrasting ecosystems and showed that β significantly affects ecosystem properties such as biomass, productivity, and N losses. A particular intermediate value of β maximizes the primary productivity and minimizes mineral N losses. In addition, contrasting β values between two plant types allow their coexistence, and the ability of one type to control nitrification modifies the patterns of coexistence with the other. We also show that species replacement dynamics do not lead to the minimization of the total mineral N pool nor the maximization of plant productivity, and consequently do not respect Tilman's R* rule. Our results strongly suggest in the two contrasted ecosystems that β has important consequences for ecosystem functioning and plant community structure.


Photostability studies of ouabain, alpha-acetyldigoxin and digoxin in solid state.
Ouabain, alpha-acetyldigoxin and digoxin were subjected to irradiation using different light sources in crystalline state and their respective yields of photoproducts were determined densitometrically. alpha-Acetyldigoxin was found to be less stable than digoxin yielding a higher percentage of photoproducts under each light source examined. Ouabain showed photostability under the conditions of investigation.


Current State and Future Possibilities in Liver Transplantation.
Due to medical and surgical progress, liver transplantation (LT) is is nowadays a routine treatment for terminal liver failure and hepatic malignancies. However, in recent years there has been a change in the indications for LT. Especially in western industrialized countries, the use of LT for chronic hepatis B and hepatitis C cirrhosis is continuously decreasing since the introduction of effective antiviral drugs. Liver cirrhosis due to non-alcoholic steatohepatitis (NASH), alcoholic liver disease and hepatocellular carcinoma (HCC) in cirrhosis are now among the leading indications for LT. Due to tremendous progress in oncology, immunology, and technical aspects, multidisciplinary cancer treatment increasingly includes LT for non-HCC hepatobiliary malignancies. Excellent 5-year survival rates of 75 to 80% can now be achieved after LT. However, in patients with liver cirrhosis, the implementation of a 'sickest first' principle for liver allocation has led to an increasing number of critically ill patients undergoing liver transplantation. This results in an increased morbidity and mortality after liver transplantation. Moreover, donor characteristics have markedly shifted to less ideal grafts due to an increasing shortage of donor organs in many countries. In this context, normothermic machine perfusion with oxygenated blood components using pulsatile flow has been shown to reduce liver damage despite a prolonged preservation time and might be able to provide viability testing for otherwise discarded organs. With favorable donor and recipient conditions, excellent long-term results can be obtained with a 10-year survival rate of close to 70%. However, in patients with a high MELD score (>30), survival rates markedly decrease by 12-18%. Future research should focus on optimization of organ allocation, optimization of immunosuppression including tolerance induction, and on increasing the donor organ pool to further improve and the numbers of successful LT.


Bis-indole-derived NR4A1 antagonists inhibit colon tumor and splenic growth and T-cell exhaustion.
There is evidence that the orphan nuclear receptor 4A1 (NR4A1, Nur77) is overexpressed in exhausted CD8 + T cells and regulates PD-L1 in tumors. This study investigated the effects of potent bis-indole-derived NR4A1 antagonists on reversing T-cell exhaustion and downregulating PD-L1 in colon tumors/cells. NR4A1 antagonists inhibited colon tumor growth and downregulated expression of PD-L1 in mouse colon MC-38-derived tumors and cells. TILs from MC-38 cell-derived colon tumors and splenic lymphocytes exhibited high levels of the T-cell exhaustion markers including PD-1, 2B4, TIM3+ and TIGIT and similar results were observed in the spleen, and these were inhibited by NR4A1 antagonists. In addition, treatment with NR4A1 antagonists induced cytokine activation markers interferon γ, granzyme B and perforin mRNAs and decreased TOX, TOX2 and NFAT in TIL-derived CD8 + T cells. Thus, NR4A1 antagonists decrease NR4A1-dependent pro-oncogenic activity and PD-L1 expression in colon tumors and inhibit NR4A1-dependent T-cell exhaustion in TILs and spleen and represent a novel class of mechanism-based drugs that enhance immune surveillance in tumors.


Insertion of percutaneous endoscopic gastrostomy tubes by a maxillofacial surgical team in patients with oropharyngeal cancer.
This study assessed the clinical outcome after insertion of a percutaneous endoscopic gastrostomy tube (PEGT) by a maxillofacial team in a series of 54 patients. The indication for PEG feeding was any patient with oropharyngeal cancer who was unlikely to return to oral feeding within 14 days. Fifty-two patients (96%) had tubes successfully inserted at the time of examination under anaesthesia (n = 19) or definitive operation (n = 33). Feeding was established at a median of 2 days (range 1-6). Median duration of tube feeding was 18 weeks (range 4-70). There were no deaths or major complications and 10 minor complications. No tube was lost or required premature removal. We conclude that insertion of a PEG tube is a procedure that can be done safely by maxillofacial surgeons.


A DNA Logic Gate Automaton for Detection of Rabies and Other Lyssaviruses.
Immediate activation of biosensors is not always desirable, particularly if activation is due to non-specific interactions. Here we demonstrate the use of deoxyribozyme-based logic gate networks arranged into visual displays to precisely control activation of biosensors, and demonstrate a prototype molecular automaton able to discriminate between seven different genotypes of Lyssaviruses, including Rabies virus. The device uses novel mixed-base logic gates to enable detection of the large diversity of Lyssavirus sequence populations, while an ANDNOT logic gate prevents non-specific activation across genotypes. The resultant device provides a user-friendly digital-like, but molecule-powered, dot-matrix text output for unequivocal results read-out that is highly relevant for point of care applications.


Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome.
DNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited. We use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3' CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3' CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3' CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3' CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions. Our results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.


Estimates of genetic parameters for stayability to consecutive calvings of Canadian Simmentals by random regression models.
Stayability to consecutive calvings was selected as a measure of cow longevity in the Canadian Simmental population. Calving performance data on 188,579 cows and culling information from the Total Herd Reporting System were used to determine whether a cow stayed in a herd for her second and later (up to the eighth) calvings, given that she had calved as 2 yr old. Binary records (n = 1,164,319) were analyzed with animal linear and threshold models including fixed effects of year of birth by season of birth by parity number and age of cow at first calving by parity number and random effects of contemporary group (CG) defined as herd of birth within year by season, animal additive genetic effect, and a cow permanent environmental (PE) effect. All random effects were Legendre polynomial regressions of the same order, defined on the scale from second to the eighth calving. Bayesian methods with Gibbs sampling were used to estimate covariance components and genetic parameters for random effects of models and selected variables on the longitudinal scale. Bayes factors and analyses of mean squared error and correlation between observed and predicted observations indicated that the linear model with regressions of order 3 was most plausible for generating the current data compared with a fixed regression and other random regression (both linear and threshold) models of order up to 4. Estimates of variances for all random effects from the best fitting model changed with the calving number. Estimates of heritability decreased in time: from 0.35 (SD = 0.006) for stayability to second calving to 0.13 (SD = 0.004) for stayability to the eighth calving. Variance due to PE effect constituted the largest part of the total variance of stayability for all longitudinal points followed by genetic and CG components. Genetic effects of stayability to different calvings were relatively highly correlated, from 0.62 (SD = 0.011) to 0.99 (SD = 0.001), and correlation decreased with the time span between calvings. Correlations for PE and CG effects showed similar trends. Animal genetic effect seemed to be less variable on the longitudinal scale compared with other random effects of the model. The first 2 principal components explained from 95% (PE effects) to 99% (genetic effect) of the total variance. The overall level of genetic stayability curve correlated well (from 0.87 to 0.99, with SD < 0.006) with genetic stayability to different calvings and therefore could be used as a single criterion in selection for stayability.


Solution structure and dynamics of a designed monomeric variant of the lambda Cro repressor.
The solution structure of a monomeric variant of the lambda Cro repressor has been determined by multidimensional NMR. Cro K56[DGEVK] differs from wild-type Cro by the insertion of five amino acids at the center of the dimer interface. 1H and 15N resonances for 70 of the 71 residues have been assigned. Thirty-two structures were calculated by hybrid distance geometry/simulated annealing methods using 463 NOE-distance restraints, 26 hydrogen-bond, and 39 dihedral-angle restraints. The root-mean-square deviation (RMSD) from the average structure for atoms in residues 3-60 is 1.03 +/- 0.44 A for the peptide backbone and 1.6 +/- 0.73 A for all nonhydrogen atoms. The overall structure conforms very well to the original design. Although the five inserted residues form a beta hairpin as expected, this engineered turn as well as other turns in the structure are not well defined by the NMR data. Dynamics studies of backbone amides reveal T1/T2 ratios of residues in the alpha2-alpha3, beta2-beta3, and engineered turn that are reflective of chemical exchange or internal motion. The solution structure and dynamics are discussed in light of the conformational variation that has been observed in other Cro structures, and the importance of flexibility in DNA recognition.


Control of individual phase relationship between coupled oscillators using multilinear feedback.
Due to various technological and medical demands, several methods for controlling the dynamical behavior of coupled oscillators have been developed. In the present study, we develop a method to control the individual phase relationship between coupled oscillators, in which multilinear feedback is used to modify the interaction between the oscillators. By carrying out a simulation, we show that the phase relationship can be well controlled by using the proposed method and the control is particularly robust when the target coupling function is selected properly.


Development and validation of a combined enzymatic-digestion/mass spectrometry assay for Tacrolimus quantitation in cardiac biopsies.
Recent studies report strategies for analysing immunosuppressive drugs in brain, liver and renal tissue, mostly in animals: we developed and validated a two steps combined enzymatic digestion/mass spectrometry assay to quantify Tacrolimus (TAC) in heart biopsies. Our aims were to avoid sample loss and sample contamination during the laboratory preparation, and to limit matrix effects in the electrospray ionization source (ESI) of the mass spectrometer. Enzymatic tissue digestion followed by a liquid-liquid drug extraction in the same vial of reaction allowed us to reach both our aims. The assay was assessed for selectivity, matrix effect, linearity, Lower Limit of Quantification (LLOQ) and Detection (LOD), accuracy and precision, according to the "Guideline on Bioanalytical Method Validation (EMA). A stable isotopically labelled (SIL) analogue (13CD2-TAC) was used as internal standard. The chromatographic separation of the analyte took 6 min. The observed linear range of quantification was 0.0162-0.520 ng in terms of TAC added to the biopsies (by 50 μL of the corresponding working solutions). The limit of detection and the lower limit of quantification (LLOQ) were 0.008 and 0.0162 ng, respectively. Both the mobile phases contained ammonium acetate and formic acid that promote the formation of ammoniated precursor ions that can be easily fragmented ([M + NH4]+, TAC m/z 821.3; 13CD2-TAC m/z 824.3). The calibration curves were generated by plotting analyte-to-internal standard peak area ratios versus TAC amount (ng) added to the biopsies, and using a weighted (1/x) linear regression. Curves were not forced to pass through the origin. Swine hearts were employed as blank matrix for all the analytical method validation procedures but, after approval by the ethics committee (by "Fondazione IRCCS Policlinico San Matteo": Protocol 20190032933), TAC was also quantified in endomyocardial biopsies from informed and consenting heart transplant patients. The study was funded by Fondazione IRCCS Policlinico San Matteo (RC08017617), as a part of the clinical studies on the maintenance of immunosuppressive therapy in cardiac transplant patients. Tacrolimus concentrations in patients biopsies were expressed as ratio between the detected amount of TAC (ng) in the tissue and the weight of the tissue itself (mg).


Aging with spinal cord injury.
The years after SCI may be associated with acceleration of the aging process because of diminished physiologic reserves and increased demands on functioning body systems. Clinicians with expertise in the treatment and prevention of SCI-specific secondary complications need to collaborate with gerontologists and primary care specialists and need to invest in the training of future physicians to ensure a continuum of accessible, cost-effective, and high-quality care that meets the changing needs of the SCI population. Managed care payers often do not adequately cover long-term disability needs to prevent secondary SCI-specific complications. In this era of increasing accountability, evidence-based clinical practice guidelines are needed to document scientific evidence and professional consensus to effectively diagnose, treat, and manage clinical conditions; to reduce unnecessary testing and procedures; and to improve patient outcomes. Longitudinal research is needed to minimize cohort effects that contribute to misinterpretation of cross-sectional findings as representative of long-term changes in health and functioning. However, longitudinal studies confound chronologic age, time since injury, and environmental change. Thus, time-sequential research, which controls for such confounding effects, is essential, as is research on the effects of gender,culture, and ethnicity. If we consider how much progress has been made over the past 50 years with respect to SCI mortality related to infectious disease, we can expect to achieve even greater progress against the effects of aging in the next 50 years. Recent developments in molecular biology regarding growth and neuro-trophic factors are bringing us closer to the goal of repairing the damaged spinal cord. The challenge remains for rehabilitation professionals to provide the most comprehensive and holistic approach to long-term follow-up, with an emphasis on health promotion and disease prevention, to postpone functional decline and enhance QOL.


Multiple quantum filtered nuclear magnetic resonance of 23Na+ in uniformly stretched and compressed hydrogels.
Stretching or compressing hydrogels creates anisotropic environments that lead to motionally averaged alignment of embedded guest quadrupolar nuclear spins such as 23Na+. These distorted hydrogels can elicit a residual quadrupolar coupling that gives an oscillation in the trajectories of single quantum coherences (SQCs) as a function of the evolution time during a spin-echo experiment. We present solutions to equations of motion derived with a Liouvillian superoperator approach, which encompass the coherent quadrupolar interaction in conjunction with relaxation, to give a full analytical description of the evolution trajectories of rank-1 (T^1±1), rank-2 (T^2±1), and rank-3 (T^3±1) SQCs. We performed simultaneous numerical fitting of the experimental 23Na nuclear magnetic resonance (NMR) spectra and rank-2 (T^2±1) and rank-3 (T^3±1) SQC evolution trajectories measured in double and triple quantum filtered experiments, respectively. We estimated values of the quadrupolar coupling constant CQ, rotational correlation time τC, and 3 × 3 Saupe order matrix. We performed simultaneous fitting of the analytical expressions to the experimental data to estimate values of the quadrupolar coupling frequency ωQ/2π, residual quadrupolar coupling ωQ/2π, and corresponding spherical order parameter S0*, which showed a linear dependence on the extent of uniform hydrogel stretching and compression. The analytical expressions were completely concordant with the numerical approach. The insights gained here can be extended to more complicated (biological) systems such as 23Na+ bound to proteins or located inside and outside living cells in high-field NMR experiments and, by extension, to the anisotropic environments found in vivo with 23Na magnetic resonance imaging.


Diurnal and nocturnal serum melatonin concentrations after treatment with continuous positive airway pressure in patients with obstructive sleep apnea.
INTRODUCTION Melatonin secretion, one of the main factors controlling the sleep-wake rhythm, may be disrupted in patients with sleep disorders. OBJECTIVES The aim of the study was to evaluate the profile of circadian melatonin secretion in patients with obstructive sleep apnea (OSA) and to assess the impact of 2-day and 3-month treatment with continuous airway pressure (CPAP) on diurnal and nocturnal serum melatonin levels. PATIENTS AND METHODS Serum melatonin levels were evaluated in 71 untreated patients with OSA and 18 healthy controls at 6 time points: 10 AM, 2 PM, 6 PM, 10 PM, 2 AM, and 6 AM. The measurements were repeated after 2 days and 3 months of CPAP treatment. RESULTS Melatonin secretion rhythm was altered in 25.4% of the patients with OSA. In patients with preserved secretion rhythm, the serum melatonin level was significantly lower at 2 AM and 6 AM, compared with healthy controls: 68.2 pg/ml (interquartile range [IQR], 30.1-109.8 pg/ml) vs 109.1 pg/ml (IQR, 63-167.9 pg/ml), P = 0.02 and 40.8 pg/ml (IQR, 20.8-73.2 pg/ml) vs 67.7 pg/ml (IQR, 32.7-131.7 pg/ml), P = 0.04, respectively. Melatonin levels did not change significantly after the 2-day and 3-month CPAP treatment. However, at 3 months, a shift of the peak melatonin concentration to 2 AM was observed in patients with an altered secretion rhythm. CONCLUSIONS OSA has a significant effect on serum melatonin levels. Neither short-term nor long-term CPAP treatment significantly changes melatonin concentrations; however, our results seem to indicate that a 3-month CPAP treatment may be helpful in restoring the physiological rhythm of melatonin secretion in patients with OSA.


Zadbimyia, a new genus of asynaptine Porricondylinae (Diptera: Cecidomyiidae) with twenty-two new species from the cloud forest of Costa Rica.
Twenty-two new species of Zadbimyia, a new genus of the tribe Asynaptini, are described from Costa Rica, the first new descriptions of Neotropical Porricondylinae (Cecidomyiidae) in modern times. The new species are: Zadbimyia aberrans, Z. anniae, Z. artborkenti, Z. browni, Z. carolinae, Z. costaricensis, Z. dubia, Z. elenae, Z. elviae, Z. holdenae, Z. inornata, Z. lasalturas, Z. marcoi, Z. membranacea, Z. minima, Z. spinapiscis, Z. talamanca, Z. tapanti, Z. viquezi, Z. wendyae, Z. zumbadoi, and Z. zurqui. All species were found during the Zurquí All-Diptera Biodiversity Inventory, in mid-elevation (1600 m) cloud forest in the central highlands of Costa Rica. A maximum of 19 species occurred at a single site. Pseudocamptomyia Parnell, a genus known from one species in northeastern United States and possibly two species in Somalia, was identified as the closest relative of Zadbimyia. Ultraviolet light traps proved to be the most effective device to collect adults of Zadbimyia. As a peculiarity in Porricondylinae, the circumfila of Zadbimyia males are multi-looped and not substantively different from the circumfila known from male Cecidomyiidi (subfamily Cecidomyiinae).


ICECAP-O, the current state of play: a systematic review of studies reporting the psychometric properties and use of the instrument over the decade since its publication.
A paper reporting the development of the ICECAP-O was published in 2006. Since then, there has been increasing interest in the use of capability-based measures within health economics and the ICECAP-O has been suggested for use in economic evaluation by decision-making bodies in the Netherlands and UK. A systematic review of studies published between January 2006 and October 2018 which have assessed the psychometric properties of ICECAP-O or utilised the measure within economic evaluation. Twenty-four studies explored the psychometric properties of ICECAP-O and 21 have utilised the measure within economic evaluation; one study reported psychometric properties as well as utilising the measure within economic evaluation. The ICECAP-O has good construct validity and responsiveness, but there is evidence of some issues relating to content validity. In the context of economic evaluation, the ICECAP-O has, to date, mainly been included as a secondary economic measure and the reporting of results is brief with minimal detail and often no discussion. Five of the economic evaluation studies combined scores from ICECAP-O with time, but each used different terminology to describe this result. Focus, in terms of publications, appears to have shifted now from assessment of psychometric properties to the utilisation of the ICECAP-O within economic evaluation. Further research is needed with respect to a decision-rule for the ICECAP measures. This additional research should also guide users in terms of appropriate analysis, terminology and presentation of results, which are in-keeping with the conceptual framework underpinning the ICECAP-O.


Journal rankings and directions for future research in health care management: A global perspective.
Despite the increasingly global nature of health care, much of the research about journal rankings and directions for future research in health care management is from a United States based viewpoint. There is a lack of information about influential journals and trends for health care management research from a global perspective. This exploratory study gathered the opinions of health care management researchers from 17 countries regarding which journals are considered most influential, popular research topics and areas needing more attention from the research community. An online survey was sent to individuals in high-income Organisation for Economic Co-operation and Development countries who were identified through author relationships, academic institution websites, editorial boards of international journals, and academic and practitioner associations in the countries of interest. Results indicate that journal rankings vary substantially from prior published studies evaluating health care management journals and international ranking lists, and the list of influential journals includes a much more diverse array of publications. Respondents also indicated a diverse number of topics for current and future research, highlighting the global complexity of the field. The implications of this study are valuable to scholars evaluating outlets for disseminating research, and highlighting areas for collaborative research in health care management globally.


Predicting emergency evacuation and sheltering behavior: a structured analytical approach.
We offer a general approach to predicting public compliance with emergency recommendations. It begins with a formal risk assessment of an anticipated emergency, whose parameters include factors potentially affecting and affected by behavior, as identified by social science research. Standard procedures are used to elicit scientific experts' judgments regarding these behaviors and dependencies, in the context of an emergency scenario. Their judgments are used to refine the model and scenario, enabling local emergency coordinators to predict the behavior of citizens in their area. The approach is illustrated with a case study involving a radiological dispersion device (RDD) exploded in downtown Pittsburgh, PA. Both groups of experts (national and local) predicted approximately 80-90% compliance with an order to evacuate workplaces and 60-70% compliance with an order to shelter in place at home. They predicted 10% lower compliance for people asked to shelter at the office or to evacuate their homes. They predicted 10% lower compliance should the media be skeptical, rather than supportive. They also identified preparatory policies that could improve public compliance by 20-30%. We consider the implications of these results for improving emergency risk assessment models and for anticipating and improving preparedness for disasters, using Hurricane Katrina as a further case in point.


Indirect effect of management support on users' compliance behaviour towards information security policies.
Health information systems are innovative products designed to improve the delivery of effective healthcare, but they are also vulnerable to breaches of information security, including unauthorised access, use, disclosure, disruption, modification or destruction, and duplication of passwords. Greater openness and multi-connectedness between heterogeneous stakeholders within health networks increase the security risk. The focus of this research was on the indirect effects of management support (MS) on user compliance behaviour (UCB) towards information security policies (ISPs) among health professionals in selected Malaysian public hospitals. The aim was to identify significant factors and provide a clearer understanding of the nature of compliance behaviour in the health sector environment. Using a survey design and stratified random sampling method, self-administered questionnaires were distributed to 454 healthcare professionals in three hospitals. Drawing on theories of planned behaviour, perceived behavioural control (self-efficacy (SE) and MS components) and the trust factor, an information system security policies compliance model was developed to test three related constructs (MS, SE and perceived trust (PT)) and their relationship to UCB towards ISPs. Results showed a 52.8% variation in UCB through significant factors. Partial least squares structural equation modelling demonstrated that all factors were significant and that MS had an indirect effect on UCB through both PT and SE among respondents to this study. The research model based on the theory of planned behaviour in combination with other human and organisational factors has made a useful contribution towards explaining compliance behaviour in relation to organisational ISPs, with trust being the most significant factor. In adopting a multidimensional approach to management-user interactions via multidisciplinary concepts and theories to evaluate the association between the integrated management-user values and the nature of compliance towards ISPs among selected health professionals, this study has made a unique contribution to the literature.


Spectrum Of Brain Abnormalities Detected On Whole Body F-18 FDG PET/CT Scan.
Positron emission tomography (PET) with integrated computed tomography (CT) is a unique modality to noninvasively scan the whole body for diagnosing, staging and assessing response to therapy in various benign and malignant diseases. 18F fluorodeoxyglucose (FDG) is the most commonly used radiotracer for PET/CT imaging in cancer patients. FDG is a glucose analogue which is the predominant substrate for brain metabolism. As the brain cells are obligate glucose consumers, the knowledge of physiologic radiotracer uptake within the brain is imperative for correct interpretation of abnormal sites of metabolism. Over 10,000 PET/CT scans have been performed at our centre in a 5 years' period. A spectrum of brain abnormalities, both benign and malignant, detected in cancer patients undergoing whole body 18F FDG PET/CT imaging has been compiled.


Quantitative studies on the fetal lipid metabolism in rats: liver fatty acid esterification and conversion into carbon dioxide, and hepatic output of triglycerides and phospholipids into serum.
Fetal lipid metabolism was studied quantitatively using the 14C-1-palmitate in vivo tracer technique and compartment analysis, and in vitro incorporation experiments. The following conclusions can be drawn from our experiments. Fetal serum free fatty acids (FFA) exchange so rapidly with the FFA of another compartment that the FFA of both compartments can be considered as one homogeneous FFA compartment. The turnover time of this compartment was calculated to be 0.76 mumol FFA/min/l through this compartment. The incorporation of fetal serum FFAs into fetal liver triglyceride fatty acids (TG-FA) and phospholipid fatty acids (PL-FA) was calculated to be 0.05 and 0.14 mumol FFA/min/l, respectively. Thus, only 16% of the fetal serum FFA is incorporated into fetal liver lipids. The fetal serum TG-FA most likely originate in the fetal liver. The fetal liver puts out 0.025 mumol TG-FA/min/l and 0.10 mumol PL-FA/min/l into the fetal serum. The turnover times of fetal serum TG-FA and PL-FA are 100 and 39 min, respectively. The fetal liver conversion rate of fatty acids (FA) into CO2 determined in vitro (0.06 mumol FA/min/l) amounts to about 25% of the rate seen in the whole rat fetus.


Predicting Emergency Visits and Hospital Admissions During Radiation and Chemoradiation: An Internally Validated Pretreatment Machine Learning Algorithm.
Patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT) may require emergency department evaluation or hospitalization. Early identification may direct preventative supportive care, improving outcomes and reducing health care costs. We developed and evaluated a machine learning (ML) approach to predict these events. A total of 8,134 outpatient courses of RT and CRT from a single institution from 2013 to 2016 were identified. Extensive pretreatment data were programmatically extracted and processed from the electronic health record (EHR). Training and internal validation cohorts were randomly generated (3:1 ratio). Gradient tree boosting (GTB), random forest, support vector machine, and least absolute shrinkage and selection operator logistic regression approaches were trained and internally validated based on area under receiver operating characteristic (AUROC) curve. The most predictive ML approach was also evaluated using only disease- and treatment-related factors to assess predictive gain of extensive EHR data. All methods had high predictive accuracy, particularly GTB (validation AUROC, 0.798). Extensive EHR data beyond disease and treatment information improved accuracy (delta AUROC, 0.056). A Youden-based cutoff corresponded to validation sensitivity of 81.0% (175 of 216 courses with events) and specificity of 67.3% (1,218 of 1811 courses without events). Interpretability is an important advantage of GTB. Variable importance identified top predictive factors, including treatment (planned RT and systemic therapy), pretreatment encounters (emergency department visits and admissions in the year before treatment), vital signs (weight loss and pain score in the year before treatment), and laboratory values (albumin level at weeks before treatment). ML predicts emergency visits and hospitalization during cancer therapy. Incorporating predictions into clinical care algorithms may help direct personalized supportive care, improve quality of care, and reduce costs. A prospective trial investigating ML-assisted direction of increased clinical assessments during RT is planned.


A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.
Here, we report the characterization of a novel hybrid D2/D3 agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D2/D3 receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, concomitant with reduced levels of aggregated α-Syn. Furthermore, D-607 was able to rescue DAergic neurons from MPTP toxicity in mice, a well-known PD neurotoxicity model, following both sub-chronic and chronic MPTP administration. Mechanistic studies indicated that possible protection of mitochondria, up-regulation of hypoxia-inducible factor, reduction in formation of α-Syn aggregates and antioxidant activity may underlie the observed neuroprotection effects. These observations strongly suggest that D-607 has potential as a promising multifunctional lead molecule for viable symptomatic and disease-modifying therapy for PD.


Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration.
As a follow-up to previous studies showing that human cortical neural progenitor cells (hNPC(ctx)) can sustain vision for at least 70 days after injection into the subretinal space of Royal College of Surgeons (RCS) rats, the authors examined how functional rescue is preserved over long periods and how this relates to retinal integrity and donor cell survival. Pigmented dystrophic RCS rats (n = 15) received unilateral subretinal injections of hNPC(ctx) at postnatal day (P) 21; control rats (n = 10) received medium alone and were untreated. All animals were maintained on oral cyclosporine A. Function was monitored serially by measuring acuity (using an optomotor test) and luminance thresholds (recording from the superior colliculus) at approximately P90, P150, and P280. Eyes were processed for histologic study after functional tests. Acuity and luminance thresholds were significantly better in hNPC(ctx)-treated animals than in controls (P < 0.001) at all time points studied. Acuity was greater than 90%, 82%, and 37% of normal at P90, P150, and P270, whereas luminance thresholds in the area of best rescue remained similar the whole time. Histologic studies revealed substantial photoreceptor rescue, even up to P280, despite progressive deterioration in rod and cone morphology. Donor cells were still present at P280, and no sign of donor cell overgrowth was seen. Long-term rescue of function and associated morphologic substrates was seen, together with donor cell survival even in the xenograft paradigm. This is encouraging when exploring further the potential for the application of hNPC(ctx) in treating retinal disease.


Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in pulmonary tuberculosis.
Pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis and is one of the most serious diseases worldwide. Circular RNAs (circRNAs) are a large class of non-coding RNAs that were identified with potential regulatory roles in disease pathogenesis and progression. In this study, we used whole transcriptome sequencing to identify circRNAs from 3 PTB patients and 3 healthy individuals to determine the expression pattern of circRNAs in blood and the circRNA molecular regulatory networks in PTB pathogenesis. One hundred and seventy differentially expressed (≥ 2-fold change) circRNAs were dysregulated in PTB, compared with in healthy individuals. Quantitative real-time polymerase chain reaction was used to validate the RNA sequencing analysis from 20 PTB patients, and the results were consistent with the sequencing data. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were applied to explore the potential circRNA functions of the significantly deregulated genes. Several immunity pathways, including endocytosis pathways in cancer, mitogen-activated protein kinase signaling pathway, human T-lymphotropic virus type 1 infection, and ubiquitin-mediated proteolysis, were involved in PTB pathogenesis. Competing endogenous RNAs (ceRNA) were constructed and inferred that aberrant expression of circRNA-associated ceRNA resulted in extensive variation in gene expression by miRNA-mediated circRNA-mRNA crosstalk interactions. Our study revealed that the circRNA-miRNA-mRNA network may shed light on the biological functions of circRNAs in PTB and provide useful information for exploring potential roles of circRNA in PTB.


Conformational Regulation and Crystalline Manipulation of PLLA through a Self-Assembly Nucleator.
Self-assembly nucleators have been increasingly used to manipulate the crystallization of PLLA due to their strong intermolecular interaction with PLLA, while the molecular mechanism of such interaction is still unrevealed. In present work, one special self-assembly nucleator (TMC-300) with relatively high solubility in PLLA matrix, is chosen to investigate how the interaction works at molecular level to promote the crystallization of PLLA mainly through time-resolved spectroscopy. The results indicate that due to the dipole-dipole NH···O═C interaction between dissolved TMC-300 and PLLA, PLLA chains are transformed into gt conformer before TMC-300 phase-separating from PLLA melt, resulting in low energy barrier to pass for the following formation of PLLA α-crystal (α-crystal is consisted of gt conformer). Once the dissolved TMC-300 starts to self-assemble into frameworks upon cooling, the transformed PLLA chains with high population of gt conformer form the primary nuclei on the surface of such self-assembling TMC-300 frameworks. For the first time, not only the heterogeneous nucleation but also the conformational regulation of PLLA chains are proved to be responsible for the high efficiency of the self-assembly nucleators (TMC-300) in promoting the crystallization of PLLA. Therefore, conformational regulation is proposed for crystalline manipulation of PLLA, and this work brings new insight on promoting the crystallization of PLLA even other polymers by regulating their molecular conformation.


Stochastic detection of motor protein-RNA complexes by single-channel current recording.
A label- and immobilization-free approach to detecting the reversible formation of complexes between nucleic acids and proteins at the single-molecule level is described. The voltage-driven translocation of individual oligoribonucleotides through a nanoscale protein pore is observed by single-channel current recordings. The oligoribonucleotide 5'-C25A(25)-3' gives rise to current blockades with an average duration of approximately 0.5 ms. In the presence of the RNA-binding ATPase P4, a viral packaging motor from bacteriophage phi8, longer events of tens to hundreds of milliseconds are observed. Upon addition of ATP the long events disappear, indicating the dissociation of the P4RNA complex. The frequency of events also depends on the concentration of P4 and the length of the oligoribonucleotide, thereby confirming the specificity of the P4RNA events. This study shows that single-channel current recordings can be used to monitor RNA-protein complex formation, thus opening up a new means to examine the motor activity of RNA- or DNA-processing enzymes.


[Characteristics of articular caps of the elbow in relation to flex-extension movement].
Considering the factors limiting flexo-extension movements of the elbow, particular importance has been given to the possible existing contact between its articular ends in the final stage of the movement. However, this factor has different importance according to the angle formed by the ulnar and humeral diaphysis with their respective epiphysis. Some authors assert that humeral and ulnar articular ends do not come into any contact during the first stage of the sigmoid cavity movement on the trochlea, according to their opinion, in fact, an angle of 45 degrees should exist between the prolongation of the humeral diaphysis axis and the lower epiphysis and the great ulnar sigmoid cavity should be oriented forward and high forming an axis that is inclined of 45 degrees the horizontal plane. In order to verify this affirmation, we have measured the width of these angles in 50 soaked humeri and 50 ulnas. The same angle has been measured in 50 radiograms of partially flexed laterally projected elbows. The mean observed values have been of about 34 degrees for the distal epiphysis-diaphysis angle in humeri and of about 25 degrees for the inclination angle of the orientation axis of the great ulnar sigmoid cavity. The results show that - when humeral epiphysis-diaphysis angle is larger or eventually equal to the ulnar one - it is sufficient that the considered angles are less than 45 degrees to get a correct and complete flexo-extension movement.


Modulation of the conformation of a membrane glycosyltransferase by specific lipids.
Fluorescence techniques were used to study conformational changes in UDPgalactose:lipopolysaccharide alpha,3-galactosyltransferase (EC 188.8.131.52). Intramolecular energy transfer was measured from the single tryptophan residue in the peptide to a pyridoxal phosphate group linked to the same peptide via a reduced Schiff's base. Significant differences in energy transfer were seen when the enzyme was studied in aqueous solution and after entry into a phospholipid-lipopolysaccharide matrix, paralleling the restoration of its catalytic activity. Further differences were seen when the structures of the phospholipids and lipopolysaccharides were changed. Application of the Förster theory indicated that the changes in energy transfer resulted from changes in distances between the chromophores and/or changes in their relative orientations. The results suggest that entry of this membrane protein into a lipid matrix induces a change in conformation of the protein and that other alternative conformations can be induced by further changes in its lipid environment.


Preliminary results of a new test for rapid diagnosis of septic arthritis with use of leukocyte esterase and glucose reagent strips.
Most currently used tools to diagnose septic arthritis are either not readily available or fail to provide real-time results. Reagent strip tests have identified infections in various body fluids. We hypothesized that combined leukocyte esterase and glucose strip tests can aid in diagnosing septic arthritis in native synovial fluid because (1) leukocyte esterase concentrations would be elevated at the infection site because of secretion by recruited neutrophils, and (2) glucose concentrations would be reduced because of bacterial metabolism. We prospectively investigated synovial fluid from consecutive patients with an atraumatic joint effusion who underwent arthrocentesis in our emergency department during a one-year period. Leukocyte esterase and glucose strip tests were performed on the synovial fluid. Synovial fluid leukocyte count, crystal analysis, Gram staining, culture, and glucose concentration results were also assessed. Nineteen fluids were classified as septic and 127 as aseptic. Considering septic arthritis to be present when the leukocyte esterase reading was positive (++ or +++) and the glucose reading was negative (-) yielded a sensitivity of 89.5% (95% confidence interval [CI], 66.9% to 98.7%), specificity of 99.2% (95% CI, 95.7% to 99.9%), positive predictive value of 94.4% (95% CI, 72.7% to 99.9%), negative predictive value of 98.4% (95% CI, 94.5% to 99.8%), positive likelihood ratio of 114, and negative likelihood ratio of 0.11. The synovial leukocyte counts and polymorphonuclear cell percentages were consistent with the semiquantitative readings on the leukocyte esterase strip tests, and the glucose concentrations were consistent with the glucose strip test results. Combined leukocyte esterase and glucose strip tests can be a useful additional tool to help confirm or rule out a diagnosis of septic arthritis.


[Social and psychological aspects of the war in Bosnia and Herzegovina 1992-1993].
Every war is the deepest compassion of political fightings turned out with weapon in purpose of biological, economic, social, political and culture destroying of people. This aggression has all these components. Aggressors are Serbia and Monte Negro, and Croatia, and extreme Serbs and Croats living in Bosnia and Herzegovina, and their purpose is the destroying of Bosnian State, and its division into ethnic rules, and making great Serbia and Croatia. This inormal dirty war (war against the civilians, there are no two armies, genocid war, destroying one population) makes injuries, illnesses. It makes hard social economic changes, which change the whole life of the population, making striking changes of spirit and life of people. The most important fact which the people have in war is fear for own family and social survival. Main characteristics of the war is the horrible violence: killing people, raping, kidnapping and torturing in the concentration camps, robbing everything that worth, and making people refugees. This is the war against the civilisation. The last consequences of all these are deep emotional changes in people and groups, and this is the biggest social and medical problem of the community. That is the theme of this project.


Adhesion of activated natural killer cells to tumor necrosis factor-alpha-treated endothelium under physiological flow conditions.
Adhesion of activated natural killer (A-NK) cells to activated and nonactivated endothelial cells in vitro was studied under dynamic flow conditions. Endothelial cells grown on glass slides were either treated with tumor necrosis factor-alpha (TNF alpha) or medium, then placed into a flow chamber over which suspensions of A-NK cells were passed using a range of defined shear stress levels. Significant numbers of binding cells could be consistently observed at shear stress levels less than 3 dyn/cm2 on TNF alpha-activated endothelium or at 0.59 dyn/cm2 on nonactivated endothelium. Stable adhesion occurred rapidly following the initial interaction of the following cells with the endothelium in the absence of detectable rolling. Pretreatment of the A-NK cells with monoclonal antibodies directed against CD18 (LFA-1) or CD49d (VLA-4) resulted in a significant reduction in the number of binding cells. Simultaneous treatment with both monoclonal antibodies eliminated all A-NK adhesion occurring over 0.5 dyn/cm2. Pretreatment of the endothelial cells with antibodies against E- or P-selectin resulted in a small but significant reduction in binding only at 0.5 dyn/cm2. The binding efficiency of the A-NK cells was similar to that previously observed for T lymphocytes under the same conditions. Once bound, approximately half of the adherent cells could resist detachment when exposed to wall shear stresses over 12 dyn/cm2. These findings indicate that A-NK cell adhesion to activated endothelium can occur under shear stress conditions which are representative of postcapillary venules and that this binding is mediated principally by both CD18 and CD49d. A-NK cell adhesion also occurs to nonactivated endothelium but only at wall shear stress levels less than 1 dyn/cm2.


Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers.
We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n = 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P < 0.001) altered plasma total cholesterol (C) levels by -40%, and the ratios of lathosterol/C by -64% and -68%, and campesterol/C by +52% and +72%, respectively, with significant differences (P < 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (-46% versus -34%, P = 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.


Immunohistochemical localization of sodium-potassium-stimulated adenosine triphosphatase and carbonic anhydrase in human colon and colonic neoplasms.
Sodium-potassium-stimulated adenosine triphosphatase and carbonic anhydrase isozymes I and II were localized immunocytochemically in adenomas, adenocarcinomas, and normal epithelium of human colon harboring non-neoplastic lesions. Non-neoplastic control colon showed carbonic anhydrase I and II in the cytoplasm of the columnar cells lining the upper half of the crypts. Antiserum to sodium-potassium-stimulated adenosine triphosphatase bound to the basolateral but not the apical plasmalemma of columnar epithelial cells. Staining was most intense in the superficial cells, which also contained carbonic anhydrase, but was also evident to a lesser degree in cells deep in the crypts. Adenomas and adenocarcinomas failed to stain for content of carbonic anhydrase but retained basolateral sodium-potassium adenosine triphosphatase positivity. The staining characteristics of colonic neoplasms for the two enzymes involved in the transport function of colonic epithelium thus resembled those of the less mature cells lining the base of normal crypts.


Ice pack test: is it obsolete?
Ophthalmologic signs are the most often presenting symptoms of patients with myasthenia gravis (MG), most common being ptosis. However, ptosis may be caused by a variety of non-myasthenic disorders; hence, the distinction between them and myasthenic ptosis is critical. A battery of diagnostic tests are available to establish the diagnosis of MG, all having their pros and cons, some being life threatening. The authors present a case of 40-year-old male who presented to them with progressive weakness and double vision in which they were successful in narrowing the differentials to myasthenia by performing a simple bed side test.


[Biometric variation of the ocular globe in myopia].
The study of correlation between myopia's pathogen and the biometrics variations of the different eye ball segments. 64 patients were included in this study: 54 patients with myopia higher than--5 diopter and 10 patients with cataracta. All patients underwent a complete ocular examination including: visual acuity determination, ocular fundus examination, automatic refractometry, keratometry. Biometry was performed with an ultra-scan system. From 64 patients, 53 were with axial myopia, 1 with myopia induced by low corneal curvature radius and 10 patients with myopia induced by a high refractive index of the lens caused by cataract. In cases with axial myopia the axial length was high (26.1 mm) with a high vitreous length (20.78 mm). In cases with index myopia, only the lens thickness and the anterior chamber depth undergo biometrics variations. Curvature myopia is the result of the decrease of the corneal curvature radius. Axial myopia is that by far the most frequently form of myopia. In this case the increases in axial length is proportionally with the degree of myopia. Index myopia is produced by the increase of the refractive index of the lens in cataract. A low corneal curvature radius less frequently than the others produces curvature myopia.


Postoperative pelvic intensity-modulated radiation therapy reduced the incidence of late gastrointestinal complications for uterine cervical cancer patients.
The aim of the study was to compare incidences of late gastrointestinal adverse events and clinical outcomes between 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) after radical hysterectomy for cervical cancer patients. Between March 2007 and May 2014, 73 cervical cancer patients with high-risk prognostic factors (pelvic lymph node metastasis and/or parametrial invasion) underwent postoperative pelvic radiation therapy (RT) after radical hysterectomy. Of these patients, 33 (45%) and 40 (55%) received 3DCRT and IMRT, respectively. Because the gastrointestinal obstruction rate after postoperative pelvic 3DCRT was high, no concurrent chemotherapy was applied until 2015. The median follow-up period for patients with 3DCRT and IMRT was 82 months (6-113) and 50 months (5-74), respectively. There was no significant difference in overall survival (OS) (4-year OS: 85% vs 78%, P = 0.744) or disease-free survival (DFS) (4-year DFS: 73% vs 64%, P = 0.696) between the two groups. Eleven (33%) and 13 (33%) patients experienced recurrence after 3DCRT and IMRT, respectively. The patients who had vaginal invasion from the postoperative pathological finding more frequently had loco-regional recurrence than the patients who did not have vaginal invasion (2.3% vs 17%, P = 0.033). Gastrointestinal obstruction was observed in 9 (27%) and 3 (7.5%) patients for 3DCRT and for IMRT, respectively (P = 0.026). Severe gastrointestinal obstruction that required surgery was observed in 6 (19%) patients, all of whom received adjuvant RT by 3DCRT. IMRT could reduce the incidence of late severe gastrointestinal obstruction after postoperative pelvic RT with a non-inferior clinical efficacy compared with 3DCRT.


Sensorimotor behaviour following incomplete cervical spinal cord injury in the rat.
Rats are one of the most commonly used species for spinal cord injury research. Since the advent of the Basso, Beattie, Bresnahan (BBB) locomotor rating scale, the majority of spinal cord injury research relies upon evaluating locomotor behaviour in thoracic spinal cord injury rat models. Slightly more than 50% of all traumatic spinal cord injuries in humans, however, occur at the level of the cervical spinal cord. Further, therapies aimed at thoracic spinal cord injuries may not be directly transferable to cervical spinal cord injuries. This could be due to (1) differences in distance between the cell bodies of injured axons and the injury site and (2) because some behaviours (e.g. stepping movements) used to evaluate the therapeutic potential of a given treatment are governed primarily by intraspinal neuronal circuitry while other behaviours (e.g. skilled reaching) require more sophisticated conscious integration of the sensorimotor system. Consequently, there is a need to develop and use experimental cervical spinal cord injury models and understand the behavioural characteristics of such models. The present review highlights the sensorimotor abilities of cervical spinal cord-injured rats, including both forelimb, hind limb, and whole body behaviours. We also provide insight into the neuroanatomic substrates important for performing a given behaviour, information which may prove essential in the development of site-directed therapeutic strategies.


Aortic Valve Replacement with the Labcor TLPB Supra™ Porcine Bioprosthesis: Intermediate Clinical and Echocardiographic Outcomes.
The Labcor TBLP Supra™ prosthesis is a second-generation tissue valve that has evolved from the Labcor TBLP™ prosthesis, first introduced in 1984. The Supra prosthesis is a triple-composite porcine valve, with no specific anticalcification treatment being used in its production other than standard tissue fixation with 0.4% glutaraldehyde. To date, more than 100,000 Supra valves have been implanted, mainly in South America. Despite this remarkably high number of implants, only marginal data exist concerning durability and safety issues. Hence, the study aim was to analyze short-term and intermediate outcomes relating to the clinical and hemodynamic performance of the Supra valve, as well as complication rates METHODS: A follow up study was initiated to evaluate outcomes and durability of the Labcor Supra prosthesis. Between September 2004 and October 2010, a total of 331 patients (mean age 75.8 ± 7.2 years; mean logistic EuroSCORE 8.5 ± 2.3%) underwent aortic valve replacement using the Supra porcine bioprosthesis. The 30-day mortality rate was 4.8% (n = 16). The overall actuarial five-year survival was 72.3 ± 4.9%, and eight-year survival was 60.4 ± 5.6%. Actuarial freedom from reoperation was 96.3 ± 2.4% after five years, and 92.5 ± 3.5% after eight years. Actuarial freedom from structural valve deterioration (SVD) was 99.7 ± 0.3% at five years, and 97.2 ± 0.8% at eight years; actuarial freedom from thromboembolism was 97.5 ± 1.0% and 95.7 ± 1.6% at these times. Actuarial freedom from event rates for endocarditis were 99.5 ± 0.3% and 96.8 ± 0.6%, and 96.1 ± 0.9% and 93.0 ± 1.4% for reoperation CONCLUSIONS: No evidence was found of increased rates of SVD. All parameters studied were comparable to those examined for other second-generation porcine prostheses. Further long-term follow up investigations are required however, for the final judgment of this prosthesis.


A Predictable Approach to Exquisite Anterior Direct Restorations: the Additive Solution.
A rapidly increasing knowledge of and value in minimally invasive dentistry has shed more light on additive bonding as an ideal solution for esthetic improvement in anterior teeth. Understanding the essentials to performing predictable composite bondings, when indicated and possible, can transform everyday treatment planning to offer enduring, functional, and visually appealing results achieved, most importantly, through additive means. By preserving natural tooth structure and seamlessly blending restorations, additive bonding represents a revolutionary approach to achieving esthetic enhancements while optimizing patient satisfaction. Improvements in the composition of new composite materials have significantly enriched the quality of end-results achievable through layered bonding in the anterior region by providing superior esthetics, durability, and seamless integration with natural teeth. This article summarizes a predictable workflow for layered composite bonding as an approach to achieving enhanced esthetics.