Comparison of management and outcomes of ED patients with acute decompensated heart failure between the Canadian and United States' settings.
Introduction The objective of this study was to compare the emergency department (ED) management and rate of admission of acute decompensated heart failure (ADHF) between two hospitals in Canada and the United States and to compare the outcomes of these patients. This was a health records review of adults presenting with ADHF to two EDs in Canada and the United States between January 1 and April 30, 2010. Outcome measures were admission to the hospital, myocardial infarction (MI), and death or relapse rates to the ED. Data were analysed using descriptive, univariate and multivariate analyses. In total, 394 cases were reviewed and 73 were excluded. Comparing 156 Canadian to 165 U.S. patients, respectively, mean age was 76.0 and 75.8 years; male sex was 54.5% and 52.1%. Canadian and U.S. ED treatments were noninvasive ventilation 7.7% v. 12.8% (p=0.13); IV diuretics 77.6% v. 36.0% (p<0.001); IV nitrates 4.5% v. 6.7% (p=0.39). There were significant differences in rate of admission (50.6% v. 95.2%, p<0.001) and length of stay in ED (6.7 v. 3.0 hours, p<0.001). Proportion of Canadian and U.S. patients who died within 30 days of the ED visit was 5.1% v. 9.7% (p=0.12); relapsed to the ED within 30 days was 20.8% v. 17.5% (p=0.5); and had MI within 30 days was 2.0% v. 1.9% (p=1.0). The U.S. and Canadian centres saw ADHF patients with similar characteristics. Although the U.S. site had almost double the admission rate, the outcomes were similar between the sites, which question the necessity of routine admission for patients with ADHF.


Nephrotic syndrome due to preeclamptic nephropathy in a hydatidiform mole and coexistent fetus.
A case study and review of the literature of 2 uncommon obstetric events associated with each other is presented. The diagnosis, treatment, and evaluation of a case of nephrotic syndrome due to preeclamptic nephropathy in a hydatidiform mole and coexistent fetus is presented. Cytogenic studies and appropriate follow-up therapy are discussed. The complete remission of renal and hypertensive complications with evacuation of the pregnancy and lack of malignant transformation is stressed and is found to be characteristic of "partial" mole.


Twelve-month outcomes of ranibizumab versus aflibercept for macular oedema in branch retinal vein occlusion: data from the FRB! registry.
To compare the efficacy of ranibizumab (0.5 mg) with aflibercept (2 mg) in the treatment of cystoid macular oedema due to branch retinal vein occlusion (BRVO) over 12 months. A multicentre, international, database observational study recruited 322 eyes initiating therapy in real-world practice over 5 years. The main outcome measure was mean change in EDTRS letter scores of visual acuity (VA). Secondary outcomes included anatomic outcomes, percentage of eyes with VA >6/12 (70 letters), number of injections and visits, time to first inactivity, switching or non-completion. Generalised mixed effect models demonstrated that mean (95% CI) adjusted 12-month VA changes for ranibizumab and aflibercept were similar (+10.8 (8.2 to 13.4) vs +10.9 (8.3 to 13.5) letters, respectively, p=0.59). The mean adjusted change in central subfield thickness (CST) was greater for aflibercept than ranibizumab (-170 (-153 to -187) µm vs -147 (-130 to -164) µm, respectively, p=0.001). The overall median (Q1, Q3) of 7 (4, 8) injections and 9 (7, 11) visits was similar between treatment groups. First grading of inactivity occurred sooner with aflibercept (p=0.01). Switching was more common from ranibizumab (37 eyes, 23%) than from aflibercept (17 eyes, 11%; p=0.002). Visual outcomes at 12 months in this direct comparison of ranibizumab and aflibercept for BRVO in real-world practice were generally good and similar for the 2 drugs, despite a greater effect of aflibercept on CST and time to first grading of inactivity.


Shikonin causes cell-cycle arrest and induces apoptosis by regulating the EGFR-NF-κB signalling pathway in human epidermoid carcinoma A431 cells.
Shikonin, a naphthoquinone pigment isolated from the Chinese herbal Zicao, has been shown to exhibit antioxidant and anticancer effects. In the present study, we investigated the antiproliferative and pro-apoptotic effects of shikonin on A431 cells and explored the underlying molecular mechanisms. In the present study, our results showed that shikonin significantly inhibited the growth of A431 cells in a concentration- and time-dependent manner, and caused cell cycle arrest by upregulation of p21 and p27, and downregulation of cyclins and cyclin-dependent kinases. In addition, shikonin evidently induced apoptosis due to decreasing Bcl-2 expression, increasing Bax expression, activating caspase and inactivating NF-κB, while pretreatment with a pan-caspase inhibitor Z-Asp-CH2-DCB abrogated shikonin-induced apoptosis. Moreover, EGF could significantly increase the NF-κB DNA-binding activity and reversed the shikonin-induced inactivation of NF-κB. As anticipated AG1478 (EGFR inhibitor) and Bay11-7082 (NF-κB inhibitor) blocked EGF-reversed the inactivation of NF-κB induced by shikonin. Our data also showed that EGF could evidently reverse the shikonin-induced decreases in cell viability and increases in apoptosis. Then, the NF-κB inhibitors such as Bay11-7082, SN50, Helenalin and the EGFR inhibitor AG1478 and its downstream inhibitor such as PI3K inhibitor LY294002 and STAT3 inhibitor Stattic dramatically blocked EGF-reversed decreases in cell viability and increases in apoptosis induced by shikonin. Collectively, our findings indicated that shikonin inhibited cell growth and caused cell cycle arrest of the A431 cells through the regulation of apoptosis. Moreover, these effects were mediated at least partially by suppressing the activation of the EGFR-NF-κB signaling pathways.


[Routines upon suspicion of driving under influence].
Norway was the first country in the world to introduce an act, in 1936, that prohibits driving with a blood alcohol concentration (BAC) above 0.5 g/kg. This Norwegian Road Traffic Act was expanded in 1959 to include illegal drugs and other medicinal psychoactive drugs. Upon suspicion of drugged driving, a clinical test for impairment (CTI) is performed and blood samples are taken. The Norwegian police have been allowed to request blood analysis for illegal and prescribed drugs affecting driving performance, even by force if drug influence is suspected. There is currently no legal limit for drugs other than alcohol. The Division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Health analyse blood samples from all drivers suspected of drugged driving in Norway. Based on results of the blood sample analysis and the CTI, the DFTDA makes a preliminary conclusion of the probability of impairment comparable to BAC above 0.5 g/kg. Then the prosecuting authority decides whether to charge the suspected driver. The impairment has to be proven to the court in each individual case. The court decision is based on the outcome of the CTI, the blood sample analyses, other information that may be given and in most cases an expert witness statement. The sentences can be conditional or unconditional imprisonment, depending on the BAC or the degree of drug impairment and withdrawal of the driving licence for a period of at least 2 years..


Regulation of guinea pig heart phosphorylase kinase by cAMP, protein kinase, and calcium.
In skeletal muscle the activation of phosphorylase kinase (PK) associated with phosphorylation of the enzyme can be measured as an increase in the pH 6.8:8.2 activity ratio. Phosphorylation leads to a 20- to 30-fold increase in PK activity (PKA) at pH 6.8 and a large decrease in the Km for phosphorylase. Perfused guinea pig hearts exposed to isoproterenol (0.3 microM) showed an increase in PKA, but without an increase in the pH 6.8:8.2 activity ratio. In a 10-fold dilution of guinea pig heart cytosol exposed to cAMP + methylisobutylxanthine, PKA was stimulated twofold at pH 7.5. Addition of exogenous protein kinase stimulated PKA fourfold. Both methods of activation were reversible and were blocked by the heat-stable inhibitor of protein kinase. Guinea pig heart PK was Ca2+-dependent requiring 0.6 microM Ca2+ for half-maximal activity. Kinetic studies indicate that the Km of guinea pig heart PK for phosphorylase b at pH 6.8 is not markedly reduced after in vitro activation (35%). This could explain the observed lack of increase in the pH 6.8:8.2 activity ratio after exposure of hearts to isoproterenol. The time course for the activation of inotropic state and the glycogenolytic pathway in perfused guinea pig hearts by isoproterenol showed that these processes were maximally activated within 25 s. However, PK remained activated for 2 min, long after the other biochemical and physiological parameters had returned to control values. These data suggest that Ca2+, not phosphorylation state, is important in regulating the return of dP/dt to control levels after beta-adrenergic stimulation.


[Systematic position and life cycle of Asymphylotrema macracetabulum comb. Nov. (Trematoda, Monorchidae)].
Asymphylotrema macracetabulum (Belous, 1953) c. n. is described and diagnosis of the new genus Asymphylotrema in the subfamily Asymphylodorinae (the fam. Monorchidae) is given. The life cycle is studied and morphological characteristics of larval stages of this trematode in intermediate (freshwater molluscs Valvata sibirica and V. amurensis) and additional (Planaria sp.) hosts is given.


A fresh morphological and functional look at dermal dendritic cells.
During the past decade, a group of cells located in the dermis and possessing a dendritic morphology have emerged from obscurity and become recognized as important members of the "dermal immune system". This group of cells is characterized by a considerable degree of immunophenotypic and functional heterogeneity. In this review, the salient features of these dermal dendritic cells are put into a dermatopathology perspective, with particular emphasis on a broad group of inflammatory and neoplastic skin diseases. There appear to be multiple subsets of dermal dendritic cells, and 17 different conditions linked to active participation of these newly recognized cells. Exactly how these different subsets of dermal dendritic cells interact amongst each other, as well as with adjacent cells such as T-lymphocytes, endothelial cells, fibroblasts, and keratinocytes in these different diseases is unclear at this time. However, isolation techniques and monoclonal antibodies capable of distinguishing these subsets, as well as functional assays, are currently available and will permit definitive conclusions to be drawn regarding their pathophysiological significance. It is highly likely that, as more data is gathered, dermal dendritic cells will be the focus of further investigative activity by dermatopathologists for the next decade, and well past the year 2000.


A marginalized MAP approach and EM optimization for pair-wise registration.
We formalize the pair-wise registration problem in a maximum a posteriori (MAP) framework that employs a multinomial model of joint intensities with parameters for which we only have a prior distribution. To obtain an MAP estimate of the aligning transformation alone, we treat the multinomial parameters as nuisance parameters, and marginalize them out. If the prior on those is uninformative, the marginalization leads to registration by minimization of joint entropy. With an informative prior, the marginalization leads to minimization of the entropy of the data pooled with pseudo observations from the prior. In addition, we show that the marginalized objective function can be optimized by the Expectation-Maximization (EM) algorithm, which yields a simple and effective iteration for solving entropy-based registration problems. Experimentally, we demonstrate the effectiveness of the resulting EM iteration for rapidly solving a challenging intra-operative registration problem.


Discrimination between precancerous and cancerous lesions of the uterine cervix by DNA measurements on tissue sections.
Morphologically typical uterine cervical biopsies were separated into normal cervices, condylomas and cervical intraepithelial neoplasias (CIN) grades I, II and III. At least 100 nuclei per lesion were measured on 4 micron Feulgen-stained sections using a Zeiss microspectrophotometer, with a variant of the plug method used to compute the nuclear DNA content. DNA distribution histograms were then decomposed into subsets of diploid, tetraploid, octoploid and aneuploid cells. The decomposition, which assumed a log-normal model of polydiploidy distribution, led to the identification of six indices: (1) the percentage of diploid cells, (2) the percentage of tetraploid cells, (3) the percentage of octoploid cells, (4) the percentage of aneuploid cells with DNA contents less than tetraploidy, (5) the percentage of aneuploid cells with DNA contents between tetraploidy and octaploidy and (6) the percentage of aneuploid cells with DNA contents greater than octoploidy. These indices, along with the mean nuclear radius, the 5c exceeding rate and the 2c deviation index, generated a nine-dimensional space. Two methods of discriminant analysis on this space showed discriminating powers of 78.22% and 87.13%, respectively, as compared to the original diagnoses. The most discriminating variable in both analyses appeared to be the percentage of octoploid cells.


Structure of melanins from the fungi Ochroconis lascauxensis and Ochroconis anomala contaminating rock art in the Lascaux Cave.
Two novel species of the fungal genus Ochroconis, O. lascauxensis and O. anomala have been isolated from the walls of the Lascaux Cave, France. The interest in these fungi and their melanins lies in the formation of black stains on the walls and rock art which threatens the integrity of the paintings. Here we report solid-state cross polarization magic-angle spinning 13C and 15N nuclear magnetic resonance (NMR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) of the melanins extracted from the mycelia of O. lascauxensis and O. anomala in order to known their chemical structure. The melanins from these two species were compared with those from other fungi. The melanins from the Ochroconis species have similar SERS and 13C and 15N NMR spectra. Their chemical structures as suggested by the data are not related to 3,4-dihydroxyphenylalanine, 5,6-dihydroxyindole or 1,8-dihydroxynaphthalene precursors and likely the building blocks from the melanins have to be based on other phenols that react with the N-terminal amino acid of proteins. The analytical pyrolysis of the acid hydrolysed melanin from O. lascauxensis supports this assumption.


Substance abuse-related mortality among middle-aged male VA psychiatric patients.
This study evaluated mortality and causes of death over a seven-year period among middle-aged male psychiatric patients with and without co-occurring substance use disorder. This cohort study examined mortality among 169,051 male Vietnam-era veterans ages 40 to 59 treated for psychiatric disorders by the U.S. Department of Veterans Affairs (VA) between April and September 1998. Demographic variables, diagnoses, and prior hospitalizations were obtained from VA electronic medical records. Mortality status was obtained from VA benefits records. Cause-of-death data were purchased from the National Death Index for a random sample of 3,383 decedents. Mortality among psychiatric patients with and without diagnosed co-occurring substance use disorders was compared by logistic regression, with controls for demographic factors, psychiatric and medical diagnoses, and prior hospitalizations. Causes of death for psychiatric patients with and without co-occurring disorders were compared by chi square analyses. Results were compared to age- and race-matched norms for the U.S. population. The risk-adjusted probability of dying was 55% higher among psychiatric patients with co-occurring substance use disorders than among those without substance use disorders (OR=1.58-1.69). Overdoses and substance abuse-linked illnesses accounted for 27.6% of deaths among psychiatric patients with co-occurring substance use disorders, compared with only 8.8% of deaths among other psychiatric patients. Substance use disorders strongly contributed to premature death among male psychiatric patients. Secondary prevention is needed to reduce substance misuse and improve medical care for substance-related illnesses among psychiatric patients with co-occurring substance use disorders.


Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma.
Bortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations. The activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m² on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m², day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled. The overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy. Bortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.


Novel PRPS1 gain-of-function mutation in a patient with congenital hyperuricemia and facial anomalies.
Phosphoribosylpyrophosphate synthetase (PRPPS) superactivity (OMIM 300661) is a rare inborn error of purine metabolism that is caused by gain-of-function mutations in the X-chromosomal gene PRPS1 (Xq22.3). Clinical characteristics include congenital hyperuricemia and hyperuricosuria, gouty arthritis, urolithiasis, developmental delay, hypotonia, recurrent infections, short stature, and hearing loss. Only eight families with PRPPS superactivity and PRPS1 gain-of-function mutations have been reported to date. We report on a 7-year-old boy with congenital hyperuricemia, urolithiasis, developmental delay, short stature, hypospadias, and facial dysmorphisms. His mother also suffered from hyperuricemia that was diagnosed at age 13 years. A novel PRPS1 missense mutation (c.573G>C, p.[Leu191Phe]) was detected in the proband and his mother. Enzyme activity analysis confirmed superactivity of PRPP synthetase. Analysis of the crystal structure of human PRPPS suggests that the Leu191Phe mutation affects the architecture of both allosteric sites, thereby preventing the allosteric inhibition of the enzyme. The family reported here broadens the clinical spectrum of PRPPS superactivity and indicates that this rare metabolic disorder might be associated with a recognizable facial gestalt.


Taxonomy of the non-yellow species of Rhizocarpon (Rhizocarpaceae, lichenized Ascomycota) in the Nordic countries, with hyaline and muriform ascospores.
The taxonomy of the non-yellow species of the genus Rhizocarpon (Rhizocarpaceae, lichenized Ascomycota) occurring in the Nordic countries, with hyaline and muriform ascospores, has been revised. Rhizocarpon amphibium, R. anaperum, R. distinctum, R. furfurosum, R. lavatum, R. petraeum, R. postumum, R. reductum, R. roridulum, R. rubescens, R. subgeminatum, R. sublavatum (reported from the study area for the first time), R. subpostumum, R. suomiense, R. timdalii, and R. umbilicatum are recognized. Their morphology, anatomy, secondary chemistry, ecology, and distribution in the Nordic countries are investigated and discussed. Distribution maps and a key to the species are provided. The most important characters for separating the treated species are pruinose/epruinose thallus, number of ascospores in asci, ascospore size and number of cells per ascospore in optical view, insoluble lichen pigments of the epihymenium and the proper excipulum, and lichen substances. Seven names are lectotypified and two are neotypified.


Steric Hindrance Assay for Secreted Factors in Stem Cell Culture.
The ex vivo expansion of hematopoietic stem cells is significantly inhibited by secreted proteins that induce negative feedback loops. The ability to effectively monitor these factors is critical for their real-time regulation and control and, by extension, enhancing stem cell expansion. Here, we describe a novel monitoring strategy for the detection of soluble signaling factors in stem cell cultures using a DNA-based sensing mechanism on a chip-based nanostructured microelectrode platform. We combine DNA hybridization engineering with antibody-capturing chemistry in an amplified steric hindrance hybridization assay. This method enables the quantification of important secreted proteins, showcased by the detection of 10 pg·mL-1 level concentrations of three proteins in stem cell culture samples. This approach is the first universal nonsandwich technique that permits pg·mL-1 level quantification of small proteins in stem cell culture media without signal loss.


[Ten years of cognitive control training for depression: an overview of findings and challenges].
2007 marks a shift in scientific literature on the cognitive vulnerabilities of depression. Preceded by a vast amount of studies exploring neuroplasticity and cognitive transfer effects, Siegle e.a. (Cognit Ther Res 2007; 31: 235-62) published the findings of a proof-of-principle study in which cognitive control training (cct) was applied to treat depression. This denotes an evolution towards clinically oriented cct studies targeting reduction of the vulnerability mechanisms of depression. Following this publication, several studies tested the effects of cct on emotional vulnerability. These studies show great variability.
 AIM: This article provides an overview summarizing the findings of cct for depression published in the last 10 years.
 METHOD: The results of a recently conducted systematic review were reviewed, with a particular interest in clinical implications and challenges.
 RESULTS: cct shows beneficial effects on indicators of depression vulnerability (e.g., stress reactivity, rumination, symptomatology). Associated literature underlines the importance of intensive training procedures, use of an affective task context and task motivation.
 CONCLUSION: cct shows potential as a clinical intervention for depression. However, several questions still need to be addressed before implementation into clinical practice is warranted.


Health selection among migrants from Mexico to the U.S.: childhood predictors of adult physical and mental health.
We tested whether positive selection on childhood predictors of adult mental and physical health contributed to health advantages of Mexican-born immigrants to the United States relative to U.S.-born Mexican Americans. We combined data from surveys conducted during 2000-2003 in Mexico and the U.S. with the same structured interview. We examined retrospective reports of childhood (i.e., < 16 years of age) predictors of adult health--education, height, childhood physical illness, childhood mental health, early substance use, and childhood adversities--as predictors of migration from Mexico to the U.S. at > or = 16 years of age. We estimated overall selection by comparing migrants to all non-migrants. We also examined selection at the family (members of families of migrants vs. members of families without a migrant) and individual (migrants vs. non-migrants within families of migrants) levels. Distinguishing between family and individual selection revealed evidence of positive health selection that is obscured in the overall selection model. In particular, respondents in families with migrants were more likely to have > or = 12 years of education (odds ratio [OR] = 1.60) and be in the tallest height quartile (OR = 1.72) than respondents in families without migrants. At both the family and individual levels, migrants are disadvantaged on mental health profiles, including a higher prevalence of conduct problems, phobic fears, and early substance use. Positive health selection may contribute to physical health advantages among Mexican immigrants in the U.S. relative to their U.S.-born descendants. Mental health advantages likely reflect a lower prevalence of psychiatric disorders in Mexico, rather than protective factors that distinguish migrants.


Electroconvulsive therapy in Ibadan.
An analysis of the result of administering electroconvulsive therapy (E.C.T.) to 292 patients suffering predominantly from psychosis and depression is presented. The results show that the courses of E.C.T. administered range from three to twenty-five. The most frequently administered course was six to eight. Favourable response to treatment was reported in all diagnostic groups immediately after completing the course but less so in cases of depression and paranoid schizophrenia. The reasons thought to account for this were discussed. It is concluded that there is need for careful selection of patients for E.C.T.


Knowledge is power: a guide to fact-based managed-care negotiations.
Signing a managed-care contract does not have to be an unnerving experience, as long as a practice administrator or physician is armed with the right information.


Postnatal Hyperoxia Exposure Durably Impairs Right Ventricular Function and Mitochondrial Biogenesis.
Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular (RV) hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of RV dysfunction and ventricular-vascular uncoupling after prematurity, remain poorly defined. Using an established model of prematurity-related lung disease, pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (fraction of inspired oxygen, 0.85) exposure for the first 14 days of life. After aging to 1 year in standard conditions, rats underwent hemodynamic assessment followed by tissue harvest for biochemical and histological evaluation. Aged hyperoxia-exposed rats developed significantly greater RV hypertrophy, associated with a 40% increase in RV systolic pressures. Although cardiac index was similar, hyperoxia-exposed rats demonstrated a reduced RV ejection fraction and significant RV-pulmonary vascular uncoupling. Hyperoxia-exposed RV cardiomyocytes demonstrated evidence of mitochondrial dysregulation and mitochondrial DNA damage, suggesting potential mitochondrial dysfunction as a cause of RV dysfunction. Aged rats exposed to postnatal hyperoxia recapitulate many features of young adults born prematurely, including increased RV hypertrophy and decreased RV ejection fraction. Our data suggest that postnatal hyperoxia exposure results in mitochondrial dysregulation that persists into adulthood with eventual RV dysfunction. Further evaluation of long-term mitochondrial function is warranted in both animal models of premature lung disease and in human adults who were born preterm.


Clinicopathologic features and immunohistochemical spectrum of 11 cases of epithelioid malignant peripheral nerve sheath tumors, including INI1/SMARCB1 results and BRAF V600E analysis.
Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare, relatively less chemosensitive sarcoma. We report clinicopathologic features of 11 epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF V600E mutation results. BRAF V600E mutation was tested by Real-time polymerase chain reaction (PCR) technique. Eleven tumors occurred in six men and five women (M:F ratio = 0.85:1) within an age range of 5-73 years (average = 44), mostly in lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were multilobular, characterized by epithelioid to round-shaped, malignant cells, along with spindle cells (three cases), "rhabdoid-like" cells (seven cases) and pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%), and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1 (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E mutation was positive in 1/8 cases, that lacked melanocytic marker expression. All patients (n = 5) were treated by surgical resection. During follow-up (n = 8, median duration = 23 months), four patients developed tumor recurrences and four developed metastasis, mostly to lymph nodes (3). Finally, four patients were alive with disease, two were alive with no evidence of disease, and two patients died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss of INI1 is useful, including in identifying rare forms of epithelioid MPNST, displaying melanocytic differentiation. Most tumors are treated by surgical resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases raises future possibility of exploring targeted therapy in those, rare epithelioid MPNSTs.


Exploring the spatial pattern of animal bites in Iran (2021-2022).
Knowledge of the spatial pattern of animal bites can be helpful for targeted resource allocation and to develop and deliver effective intervention programs. The aim of this study was to explore the spatial pattern of the animal bites in Iran during 2021-2022. Animal bite cases from all provinces and counties in Iran were obtained from a nationally based registry. Global Moran's I was applied to check spatial autocorrelation. The spatially adjusted standardized incidence ratios (SIRs) were estimated using the Besag, York, and Mollie (BYM) model. Spatial clusters were identified by local indicators of spatial association (LISA) and purely spatial scan statistic. A total of 260,470 animal bites were registered during the study period. There was a positive spatial autocorrelation (global Moran's I=0.27, p-value=0.001). The majority of SIRs greater than 1.00 was found in counties in the northern belt of Iran (e.g., observed greater than expected animal bites). LISA found that approximately 7% of counties in the north and northeast, 18% in the west and south, and 3% in the central part of Iran were significant hot spots, cold spots, and spatial outliers (p-value≤0.05). Spatial scan statistic detected primary hot spot cluster in the counties in the Mazandaran and Alborz provinces (Relative Risk=2.56, p-value<0.001), while primary cold spot cluster involved counties in Kurdistan and Kermanshah province (0.37, <0.001). Animal bites were unevenly distributed in Iran. Further prevention and control programs as well as appropriately resource allocation are needed in order to reduce the observed animal bites spatial disparity.


cDNA cloning and expression of intracellular platelet-activating factor (PAF) acetylhydrolase II. Its homology with plasma PAF acetylhydrolase.
Platelet-activating factor (PAF) acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position, is widely distributed in plasma and tissues. We previously demonstrated that tissue cytosol contains at least two types of PAF acetylhydrolase, isoforms Ib and II, and that isoform Ib is a heterotrimer comprising 45-, 30-, and 29-kDa subunits, whereas isoform II is a 40-kDa monomer. In this study, we isolated cDNA clones of bovine and human PAF acetylhydrolase isoform II. From the longest open reading frame of the cloned cDNAs, both bovine and human PAF acetylhydrolases II are predicted to contain 392 amino acid residues and to exhibit 88% identity with each other at the amino acid level. Both enzymes contain a Gly-X-Ser-X-Gly motif that is characteristic of lipases and serine esterases. Expression of isoform II cDNA in COS7 cells resulted in a marked increase in PAF acetylhydrolase activity. An immunoblot study using an established monoclonal antibody against the bovine enzyme revealed that the recombinant protein exists in the membranous fraction as well as the soluble fraction. Isoform II is expressed most abundantly in the liver and kidney in cattle, but low levels were also observed in other tissues. The amino acid sequence deduced from the cDNA of isoform II had no homology with any subunit of isoform Ib. Interestingly, however, the amino acid sequence of isoform II showed 41% identity with that of plasma PAF acetylhydrolase. Combined with previous data demonstrating that isoform II shows similar substrate specificity to plasma PAF acetylhydrolase, these results indicate that tissue type isoform II and the plasma enzyme may share a common physiologic function.


Bis(1,4-diazo-niabi-cyclo-[2.2.2]octa-ne) di-μ-chlorido-bis-[tetra-chlorido-anti-monate(III)] dihydrate.
The title salt, (C6H14N2)2[Sb2Cl10]·2H2O, was obtained by slow evaporation of an acidic solution of 1,4-di-aza-bicyclo-[2.2.2]octane and SbCl3. The crystal structure consists of (C6H14N2)(2+) cations, [Sb2Cl10](4-) double octa-hedra and lattice water mol-ecules. All mol-ecular components are situated on special positions. The cation and the lattice water mol-ecule exhibit mirror symmetry, whereas the anion has site symmetry 2/m. The cations, anions and water mol-ecules are alternately arranged into columns along [010]. Individual columns are joined into layers extending along (001). Intra-layer N-H⋯O and inter-layer N-H⋯Cl hydrogen-bonding inter-actions lead to the formation of a three-dimensional network.


Plasmapheresis in a case of acute kidney injury with severe hemolysis and thrombocytopenia due to hematotoxic (Russell's viper) snake bite.
We present a case of a male patient after being bitten by a vasculotoxic snake (Russell's viper) with severe hemolysis, thrombocytopenia, and acute kidney injury requiring hemodialysis. As attempt to administer anti-snake venom (ASV) failed because of development of anaphylactic reaction, a single session of plasmapheresis was done to stop hemolysis and fall in platelets, which was refractory to all other measures and proved to be a lifesaving procedure in this patient. The role of plasmapheresis in the management of snakebite victims is yet to be established, but can be beneficial in snake bite victims refractory to ASV or nonavailability of ASV or intolerant to ASV as in this case.


Intestinal fistula complicating pancreatic abscess.
Intestinal fistulization following acute pancreatitis is a complication of abscess formation and may occur after initial surgical drainage. It should be suspected in anyone with protracted pancreatitis in whom an abdominal mass suddenly disappears or in whom gastrointestinal bleeding develops. Although transient improvement may occur, decompression will often be incomplete and will usually be followed by recurrent sepsis or severe life threatening hemorrhage. For this reason, spontaneous fistulization into the intestine does not eliminate the need for adequate surgical drainage. With fistulas into the colon, drainage should be combined with proximal diverting colostomy. Some duodenal fistulas may respond to abscess drainage and intravenously administered hyperalimentation, while others may require drainage plus conversion from a side to an end fistula.


Discovery of Potent Inhibitors for the Large Neutral Amino Acid Transporter 1 (LAT1) by Structure-Based Methods.
The large neutral amino acid transporter 1 (LAT1) is a promising anticancer target that is required for the cellular uptake of essential amino acids that serve as building blocks for cancer growth and proliferation. Here, we report a structure-based approach to identify chemically diverse and potent inhibitors of LAT1. First, a homology model of LAT1 that is based on the atomic structures of the prokaryotic homologs was constructed. Molecular docking of nitrogen mustards (NMs) with a wide range of affinity allowed for deriving a common binding mode that could explain the structure-activity relationship pattern in NMs. Subsequently, validated binding hypotheses were subjected to molecular dynamics simulation, which allowed for extracting a set of dynamic pharmacophores. Finally, a library of ~1.1 million molecules was virtually screened against these pharmacophores, followed by docking. Biological testing of the 30 top-ranked hits revealed 13 actives, with the best compound showing an IC50 value in the sub-μM range.


Different mechanistic requirements for prokaryotic and eukaryotic chaperonins: a lattice study.
The folding of many proteins in vivo and in vitro is assisted by molecular chaperones. A well-characterized molecular chaperone system is the chaperonin GroEL/GroES from Escherichia coli which has a homolog found in the eukaryotic cytosol called CCT. All chaperonins have a ring structure with a cavity in which the substrate protein folds. An interesting difference between prokaryotic and eukaryotic chaperonins is in the nature of the ATP-mediated conformational changes that their ring structures undergo during their reaction cycle. Prokaryotic chaperonins are known to exhibit a highly cooperative concerted change of their cavity surface while in eukaryotic chaperonins the change is sequential. Approximately 70% of proteins in eukaryotic cells are multi-domain whereas in prokaryotes single-domain proteins are more common. Thus, it was suggested that the different modes of action of prokaryotic and eukaryotic chaperonins can be explained by the need of eukaryotic chaperonins to facilitate folding of multi-domain proteins. Using a 2D square lattice model, we generated two large populations of single-domain and double-domain substrate proteins. Chaperonins were modeled as static structures with a cavity wall with which the substrate protein interacts. We simulated both concerted and sequential changes of the cavity surfaces and demonstrated that folding of single-domain proteins benefits from concerted but not sequential changes whereas double-domain proteins benefit also from sequential changes. Thus, our results support the suggestion that the different modes of allosteric switching of prokaryotic and eukaryotic chaperonin rings have functional implications as it enables eukaryotic chaperonins to better assist multi-domain protein folding.


A dual function of FGF signaling in Xenopus left-right axis formation.
Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). Although the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development is conserved, diverging results from different model organisms suggest a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel with FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow-sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification; namely, for generating and sensing leftward flow. Moreover, our findings in Xenopus demonstrate that FGF functions in LR development share more conserved features across vertebrate species than previously anticipated.


Assistant practitioners: their role with children in secondary care.
Assistant practitioners (APs) can help to address a variety of locally or nationally recognised deficits in healthcare services to children and their families. However, as well as training and supervision, APs should have formal registration, and the role should be continuously appraised as it develops. The ways in which APs can support clinical nursing teams in delivering secondary health care to children, young people and their families is discussed.


[Impact of changes in the amino acid sequence of the "a" determinant on the diagnostic capacities of test systems for the detection of HBsAg].
The diagnostic capacities of 4 commercial test systems were comparatively estimated for the detection of HBsAg, by applying a panel of samples with the established amino acid sequence of the "a" determinant of HBsAg. The Roche Elecsys HBsAg test system demonstrated the highest sensitivity - the maximum HBsAg concentrations were found in 19 of 31 cases. Escape mutations in the major hydrophilic region (MHR) of HBsAG (P120S, M133T) were responsible for differences in the sensitivity of 4 test systems by 10- to 40-fold. There were also samples that showed differences in the diagnostic capacities of the test systems to detect HBsAg, but without amino acid replacements in the area of the "a" determinant, which seems to be associated with amino acid replacements in other regions of HBsAg.


Group selective aptamers: Broad-spectrum recognition of target groups in Cronobacter species and implementation of electrochemical biosensors as receptors.
Aptamers are a versatile class of receptors with a high affinity and selectivity for specific targets. Although their ability to recognize individual targets has been extensively studied, some scenarios require the development of receptors capable of identifying all target groups. This study investigated the use of aptamers to achieve the broad-spectrum recognition of groups instead of individual targets. Aptamers were screened for selectively distinct groups of Cronobacter species associated with foodborne diseases. Seven Cronobacter spp. were divided into Group A (C. sakazakii, C. malonaticus, C. turicensis, and C. muytjensii) and Group B (C. dublinensis, C. condimenti, and C. universalis). Aptamers with exclusive selectivity for each group were identified, allowing binding to the species within their designated group while excluding those from the other group. The screened aptamers demonstrated reliable affinity and specificity with dissociation constants ranging from 1.3 to 399.7 nM for Group A and 4.0-24.5 nM for Group B. These aptamers have also been successfully employed as receptors in an electrochemical biosensor platform, enabling the selective detection of each group based on the corresponding aptamer (limit of detection was 7.8 and 3.2 CFU for Group A and Group B, respectively). The electrochemical sensor effectively detected the extent of infection in each group in powdered infant formula samples. This study highlights the successful screening and application of group-selective aptamers as sensing receptors, emphasizing their potential for diverse applications in different fields such as food safety, environmental monitoring, and clinical diagnostics, where the selective biosensing of target groups is crucial.


Na(+)-dependent purine nucleoside transporter from human kidney: cloning and functional characterization.
Many purine nucleosides and their analogs are actively transported in the kidney. Using homology cloning strategies and reverse transcriptase-polymerase chain reactions, we isolated a cDNA encoding a Na(+)-dependent nucleoside transporter, hSPNT1, from human kidney. Functional expression in Xenopus laevis oocytes identified hSPNT1 as a Na(+)-dependent nucleoside transporter that selectively transports purine nucleosides but also transports uridine. The Michaelis constant (K(m)) of uridine (80 microM) in interacting with hSPNT1 was substantially higher than that of inosine (4.5 microM). hSPNT1 (658 amino acids) is 81% identical to the previously cloned rat Na(+)-nucleoside transporter, SPNT, but differs markedly from SPNT in terms of its primary structure in the NH2 terminus. In addition, an Alu repetitive element (approximately 282 bp) is present in the 3'-untranslated region of the hSPNT1 cDNA. Northern analysis revealed that multiple transcripts of hSPNT1 are widely distributed in human tissues including human kidney. In contrast, rat SPNT transcripts are absent in kidney and highly localized to liver and intestine. The hSPNT1 gene was localized to chromosome 15. This is the first demonstration of a purine nucleoside transporter in human kidney.


Barriers to development: pushing the boundaries.
Why some countries have failed to create democracy, wealth and happiness for their people is one of the great questions of our time. This essay encompasses a description of the multiple barriers to development that may have different characteristics, according to the context and the social structures that maintain these conditions. It would be arrogant to pretend to have all the solutions for these problems.


Fibroblast growth factor 1attenuates 6-hydroxydopamine-induced neurotoxicity: an in vitro and in vivo investigation in experimental models of parkinson's disease.
Parkinson's disease (PD) is a degenerative disorder of the central nervous system and is characterized by motor system disorders resulting in loss of dopamine producing brain cells. Acidic fibroblast growth factor, also called FGF1, promotes the survival of neurons. The aims of the present study were to confirm FGF1 could protect neurons cultures from 6-hydroxydopamine (6-OHDA) toxicity in vitro and in vivo. Our results demonstrated FGF1 administration improved the motor function recovery, increased the TH-positive neurons survival and up-regulated the levels of neurotransmitters in PD rats. Meanwhile, FGF1 prevents the death of DA neuron at least in part by reducing the levels of α-synuclein and ER stress. The administration of FGF1 activated downstream signals PI3K/Akt and ERK1/2. In conclusion, FGF1 diminished α-synuclein neurotoxicity by down regulating ER stress mediators and the level of apoptosis, and these effects may underlying the activation of the PI3K/Akt and ERK1/2 signal pathway.


An ADAM17 selective inhibitor promotes glucose uptake by activating AMPK.
AMPK activation promotes glucose and lipid metabolism. Here, we found that our previously reported ADAM17 inhibitor SN-4 activates AMPK and promotes membrane translocation and sugar uptake of GLUT4. AMPK inhibitor dorsomorphin reversed this effect of SN-4, confirming that the effect is mediated by AMPK activation. In addition, SN-4 inhibited lipid accumulation in HepG2 under high glucose conditions by promoting lipid metabolism and inhibiting lipid synthesis. Although lactic acidosis is a serious side effect of biguanides such as metformin, SN-4 did not affect lactate production. Furthermore, SN-4 was confirmed to inhibit the release of TNF-α, a causative agent of insulin resistance, from adipocytes. In diabetes treatment, it is important to not only regulate blood sugar levels but also prevent complications. Our findings reveal the therapeutic potential of SN-4 as a new antidiabetic drug that can also help prevent future complications.


Richter Transformation Arising From Chronic Lymphocytic Leukemia.
This article presents a case of a patient diagnosed with an indolent form of chronic lymphocytic leukemia (CLL). He was being followed with close observation when he was diagnosed with Richter transformation, an aggressive lymphoma that develops from CLL. The development of Richter transformation carries a poor prognosis, in part, because of underlying molecular changes that give rise to the transformation. The prognosis also relates to the difficulty in the patient's ability to receive chemotherapy because of poor marrow reserves from the disease or the residual impact of prior treatments. Advanced practice nurses who follow patients with CLL need to be aware of the potential for Richter transformation.


Inhibition with simultaneous spontaneous reactivation and aging of acetylcholinesterase by organophosphorus compounds: Demeton-S-methyl as a model.
The kinetic analysis of esterase inhibition by acylating compounds (organophosphorus, carbamates and sulfonylfluorides) sometimes cannot yield consistent results by fitting simple inhibition kinetic models to experimental data of complex systems. In this work kinetic data were obtained for demeton-S-methyl (DSM) with human acetylcholinesterase in two kinds of experiments: (a) time progressive inhibition with a range of concentrations, (b) progressive spontaneous reactivation starting with pre-inhibited enzyme. DSM is an organophosphorus compound used as pesticide and considered a model for studying the dermal exposure of nerve agents such as VX gas. A kinetic model equation was deduced with four different molecular phenomena occurring simultaneously: (1) inhibition; (2) spontaneous reactivation; (3) aging; and (4) ongoing inhibition (inhibition during the substrate reaction). A 3D fit of the model was applied to analyze the inhibition experimental data. The best-fitting model is compatible with a sensitive enzymatic entity. The second-order rate constant of inhibition (ki = 0.0422 μM-1 min-1), the spontaneous reactivation constant (ks = 0.0202 min-1) and the aging constant (kg = 0.0043 min-1) were simultaneously estimated. As an example for testing the model and approach, it was tested also in the presence of 5 % ethanol (conditions as previously used in the literature), the best fitting model is compatible with two apparent sensitive enzymatic entities (17 % and 83 %) and only one spontaneously reactivates and ages. The corresponding second-order rate constants of inhibition (ki = 0.0354 and 0.0119 μM-1 min-1) and the spontaneous reactivation and aging constants for the less sensitive component (kr = 0.0203 min-1 and kg = 0.0088 min-1) were estimated. The results were also consistent with a significant ongoing inhibition. These parameters were similar to those deduced in spontaneous reactivation experiments of the pre-inhibited samples with DSM in the absence or presence of ethanol. The two apparent components fit was interpreted by an equilibrium between ethanol-free and ethanol-bound enzyme. The consistency of results in inhibition and in spontaneous reactivation experiments was considered an internal validation of the methodology and the conclusions.


Population viability analysis of plant and animal populations with stochastic integral projection models.
Integral projection models (IPM) make it possible to study populations structured by continuous traits. Recently, Vindenes et al. (Ecology 92:1146-1156, 2011) proposed an extended IPM to analyse the dynamics of small populations in stochastic environments, but this model has not yet been used to conduct population viability analyses. Here, we used the extended IPM to analyse the stochastic dynamics of IPM of small size-structured populations in one plant and one animal species (evening primrose and common lizard) including demographic stochasticity in both cases and environmental stochasticity in the lizard model. We also tested the accuracy of a diffusion approximation of the IPM for the two empirical systems. In both species, the elasticity for λ was higher with respect to parameters linked to body growth and size-dependent reproduction rather than survival. An analytical approach made it possible to quantify demographic and environmental variance to calculate the average stochastic growth rate. Demographic variance was further decomposed to gain insights into the most important size classes and demographic components. A diffusion approximation provided a remarkable fit to the stochastic dynamics and cumulative extinction risk, except for very small populations where stochastic growth rate was biased upward or downward depending on the model. These results confirm that the extended IPM provides a powerful tool to assess the conservation status and compare the stochastic demography of size-structured species, but should be complemented with individual based models to obtain unbiased estimates for very small populations of conservation concern.


COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury.
Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory responses playing an important role in this process. COG1410, a mimetic peptide of apolipoprotein E, has demonstrated protective potential in the central nervous system, but its effects on retinal IR injury remain unexplored. In this study, we established a mouse model of retinal IR injury to investigate the effects of COG1410 on retinal microglia and RGCs. We observed CD16/32-marked and CD206-marked microglia and RGCs using immunofluorescence staining, detected the expression of inflammatory factors by PCR, and evaluated retinal apoptosis with TUNEL staining. We further investigated the potential mechanism by detecting the expression of key proteins via Western blot. The results reveal that COG1410 decreased the number of CD16/32-marked microglia and increased the number of CD206-marked microglia, alleviated the expression of IL-1β and TNF-α, and reduced the loss of RGCs by inhibiting the mitochondrial-related apoptotic pathway. COG1410 was found to increase the expression of ERK1/2 and Nr4a1 but decrease the expression of NF-κB. The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases.


Glycolysis inhibition by palmitate in renal cells cultured in a two-chamber system.
A major shortcoming of renal proximal tubular cells (RPTC) in culture is the gradual modification of their energy metabolism from the oxidative type to the glycolytic type. To test the possible reduction of glycolysis by naturally occurring long-chain fatty acids, RPTC were cultured in a two-chamber system, with albumin-bound palmitate (0.4 mM) added to the basolateral chamber after confluency. Twenty-four hours of contact with palmitate decreased glycolysis by 38% provided that carnitine was present; lactate production was decreased by 38%, and the decrease in glycolysis resulted from a similar decrease of basolateral and apical net uptake of glucose. In contrast to the previously described effect of the nonphysiological oxidative substrate heptanoate, palmitate promoted a long-term decrease in lactate production and sustained excellent cellular growth. After 4 days of contact, decreased glycolysis was maintained even in the absence of carnitine and resulted from a decrease of basolateral uptake only, suggestive of long-term regulation different from the earlier effects. Thus, although cultured RPTC lost their oxidative phenotype, they exhibited a type of regulation (Randle effect) that is found in the oxidative-type but not in the glycolytic-type tissues, therefore unmasking a regulative capacity barely detectable in fresh RPTC. Low PO2 (50 mmHg in the apical chamber) could be a major cause of elevated glycolysis and could hinder the effects of palmitate.


Placental transfer of quazepam in mice.
The disposition of 14C-quazepam following a single 5-mg/kg po dose was studied at the postembryonic period (day 12 of pregnancy) and near-term (day 18 of pregnancy). In both 12- and 18-day pregnant mice, radioactivity from the quazepam dose was widely distributed in the maternal tissues, with the highest levels in the liver and kidneys. At the time points analyzed (1, 5, and 24 hr post-dose), radioactivity levels in the fetus were consistently 44% of the maternal plasma levels in 12-day pregnant mice. In 18-day pregnant mice, fetal radioactivity levels at these time points were consistently equal to or slightly greater than maternal plasma levels. This indicates that radioactivity was taken up and eliminated from fetal tissues at rates that were reasonably similar to those in corresponding maternal tissues. No accumulation of radioactivity was observed in the fetus or in maternal tissues in either the 12-day or the 18-day pregnant mice. In 18-day pregnant mice, concentrations of quazepam and its metabolites were measured either by gas-liquid chromatography or thin layer radiochromatography. In the maternal plasma, concentrations of quazepam, its first-formed metabolite, 2-oxoquazepam, and 3-hydroxy-2-oxoquazepam were relatively low at all time points; levels of N-desalkyl-2-oxoquazepam and 3-hydroxy-N-desalkyl-2-oxoquazepam (HDOQ) were much higher. Fetal levels of unchanged drug and metabolites were generally less than or equal to maternal plasma levels, except for HDOQ levels, which were higher in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of partnerships in U.S. Food Policy Council policy activities.
Food Policy Councils (FPC) help to identify and address the priorities of local, state, and regional food systems with the goal of improving food systems through policy. There is limited research describing FPCs' strategies for accomplishing this goal. As part of a larger study examining FPC policy efforts, this paper investigates the role of partnerships in food systems policy change. We conducted interviews with representatives from 12 purposefully selected FPCs in the United States and 6 policy experts identified by the selected FPC representatives to document and describe their policy work. One theme that emerged from those interviews was the role of partners. Interviewees described a range of partners (e.g., stakeholders from government, business, and education) and credited FPC partnerships with advancing their policy goals by increasing the visibility and credibility of FPCs, focusing their policy agenda, connecting FPCs to key policy inputs (e.g., local food community knowledge and priorities), and obtaining stakeholder buy-in for policy initiatives. Partnerships were also described as barriers to policy progress when partners were less engaged or had either disproportionate or little influence in a given food sector. Despite these challenges, partnerships were found to be valuable for FPCs efforts to effectively engage in the food policy arena.


Breast cancer associated with primary hyperparathyroidism: a nested case control study.
Primary hyperparathyroidism (pHPT) is associated with an increased risk of developing breast cancer, but little is known about the underlying factors. The aim of this study was to compare women with a history of pHPT and a reference population in terms of standard factors predictive of prognosis and response to therapy for breast cancer. We analyzed data collected from the National Swedish Cancer Register and from two regional oncologic center registries. Seventy-one women with breast cancer and a history of parathyroid adenomectomy were compared with 338 matched controls with breast cancer only. Tumor size, stage, hormone receptor status, lymph node status, cause of death, and cumulative survival were analyzed. The mean age was 69 ± 11 years (95% confidence interval [CI]: 68-70) in both groups and the mean time interval between the parathyroid surgery and breast cancer diagnosis was 91 ± 68 months (95% CI: 72-111). There were no differences between the two groups regarding size, stage, lymph node metastases, or survival, but none of the cases with a history of pHPT were found in Stage III or IV. In conclusion, factors predictive of prognosis and response to therapy in women with a history of pHPT and breast cancer are similar to those in breast cancer patients without pHPT.


[The course of affective disorders--a registry study].
In recent years, studies of the risk of recurrence in affective disorder in relation to the number of prior episodes have given contradictory results. Survival analysis was used to calculate the rate of recurrence after successive episodes in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. Totally, 20,350 first-admission patients were discharged with a diagnosis of affective disorder, depressive or manic/circular type. The rate of recurrence increased with the number of previous episodes in both unipolar and bipolar disorder. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the rate of recurrence was the same for the two disorders. The course of severe unipolar and bipolar disorder seems to be progressive in nature despite the effect of treatment.


Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease.
Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (±SD) of 67 ± 10 and 65 ± 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2 (p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.


The value of post-mortem CT in neonaticide in case of severe decomposition: description of 12 cases.
In cases of neonaticide with delayed finding of the body, interpretation of autopsy results can be difficult because of decomposition. Postmortem computed tomography (PMCT) has become an increasingly popular tool in the (pediatric) forensic field. We performed a retrospective study to compare the outcome of PMCT with autopsy results in suspected neonaticide, in neonates found more than one week after their demise. We compared the performance of both methods on (1) determining gestational age, (2) differentiating between live birth and still birth and (3) determining cause of death. We selected all consecutive neonaticide cases with an estimated postmortem interval longer than one week, who underwent a forensic autopsy including a total body PMCT in the Netherlands Forensic Institute in the period 2008-2012. Both a pathologist and radiologist scored gestational age, signs of live birth and cause of death for each case. 22 cases of neonaticide were identified in the study period, of which 15 cases were estimated to be found more than 1 week after death. In 12 of these a total body PMCT was performed. In all cases, late postmortem changes were present. Gestational age could be assessed with PMCT in 100% of the cases and with autopsy in 58% of the cases. In all cases neither PMCT nor autopsy was able to assess live birth and cause of death. PMCT is a better tool for estimating gestational age in case of suspected neonaticide with late postmortem changes compared to autopsy and should therefore be a standard part of the work-up. Signs of live birth and cause of death could not be determined with neither of the methods, an adjusted post mortem examination including limited autopsy for these cases might be developed.


Lack of hepatotoxic effects of parenteral ketorolac in the hospital setting.
No large controlled studies to date have examined the hepatic safety of parenteral ketorolac, which is used to treat acutely ill hospitalized patients who may be at greatest risk of liver injury. To measure the association between the use of parenteral ketorolac and subsequent liver injury. A nonexperimental cohort study conducted in 35 hospitals in the greater Philadelphia, Pa, region examined 10,272 courses of parenteral ketorolac (the exposed group) and 10,247 courses of parenteral opioid (the comparison group). Liver injury was defined by a modified international consensus definition that relied exclusively on liver function tests. Proportional hazards regression was used to calculate the rate ratio and 95% confidence interval for the association between ketorolac exposure and the occurrence of liver injury, controlling for potentially confounding factors, and to explore the possible effects of duration and dose. The incidence of liver injury was 1.0% in the ketorolac group and 1.2% in the opioid group, yielding an unadjusted rate ratio of 0.77 (95% confidence interval, 0.59 1.01). Simultaneously adjusting for multiple potentially confounding factors did not change this result. There was no evidence for a duration-response relationship (P = .96) or a dose-response relationship (P = .23). We were unable to identify any subgroups that were susceptible to possible hepatotoxic effects of parenteral ketorolac. This study failed to find evidence of a hepatotoxic effect of parenteral ketorolac use in the hospital setting and provides strong evidence against the existence of a clinically meaningful association between exposure to parenteral ketorolac in the hospital setting and liver injury.


"Informed consent" and disclosure of risks in medical treatment: some recent developments.
This paper discusses the implications for the doctor/patient relationship of the House of Lords' decision in Sidaway v Royal Bethlem Hospital (1985). In this decision the House of Lords rejected the "informed consent" doctrine developed in the United States in relation to the doctor's duty to disclose risks involved in medical procedures, favouring an approach in which the matter of disclosure is treated as an aspect of the doctor's duty of care towards the patient. The paper seeks to criticize this approach on the basis that it does not give sufficient protection to the patient's right to decide whether to consent to medical procedures.


The persuasiveness of synthetic speech versus human speech.
Is computer-synthesized speech as persuasive as the human voice when presenting an argument? After completing an attitude pretest, 193 participants were randomly assigned to listen to a persuasive appeal under three conditions: a high-quality synthesized speech system (DECtalk Express), a low-quality synthesized speech system (Monologue), and a tape recording of a human voice. Following the appeal, participants completed a posttest attitude survey and a series of questionnaires designed to assess perceptions of speech qualities, perceptions of the speaker, and perceptions of the message. The human voice was generally perceived more favorably than the computer-synthesized voice, and the speaker was perceived more favorably when the voice was a human voice than when it was computer synthesized. There was, however, no evidence that computerized speech, as compared with the human voice, affected persuasion or perceptions of the message. Actual or potential applications of this research include issues that should be considered when designing synthetic speech systems.


[Hypophosphatemic oncogenic osteomalacia].
The first case of oncogen osteomalacia in Hungary is reported, to draw the attention of the medical profession to it and to present the new data about its pathomechanism. Pathological hip fracture caused by hypophosphataemic osteomalacia due to isolated renal phosphate wasting was found in a previously healthy 19 years old sportsman. In spite of daily 1.5 micrograms calcitriol treatment and phosphate supplementation, hypophosphataemia persisted for 13 years and he needed regular indometacin medication for his bone pain. During that time an 1.5 cm gingival tumour was found and radically removed. The serum phosphate level returned to normal in a few hours after the operation (preoperative 0.51, after 2, 4 and 8 hours 0.61, 0.68 and 0.79 mmol/l respectively), and remained normal without calcitriol. The histological examination showed epulis with fibroblast and vascular cell proliferation, which has never been previously reported in connection with oncogenic osteomalacia. The pain resolved after 3 months and the bone density became normal in one year. Oncogenic osteomalacia must be considered in every case presenting with atypical hypophosphataemic osteomalacia. Careful dental examination is needed also in the course of search for the underlying tumour. Every tumour-like growth, even the common epulis, has to be operated radically and serum phosphate monitored in the postoperative period in all such cases.


Genetic analysis of diversity within a Chinese local sugarcane germplasm based on start codon targeted polymorphism.
In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic diversity among 107 sugarcane accessions within a local sugarcane germplasm collection. These primers amplified 176 DNA fragments, of which 163 were polymorphic (92.85%). Polymorphic information content (PIC) values ranged from 0.783 to 0.907 with a mean of 0.861. Unweighted pair group method of arithmetic averages (UPGMA) cluster analysis of the SCoT marker data divided the 107 sugarcane accessions into six clusters at 0.674 genetic similarity coefficient level. Relatively abundant genetic diversity was observed among ROC22, ROC16, and ROC10, which occupied about 80% of the total sugarcane acreage in China, indicating their potential breeding value on Mainland China. Principal component analysis (PCA) partitioned the 107 sugarcane accessions into two major groups, the Domestic Group and the Foreign Introduction Group. Each group was further divided based on institutions, where the sugarcane accessions were originally developed. The knowledge of genetic diversity among the local sugarcane germplasm provided foundation data for managing sugarcane germplasm, including construction of a core collection and regional variety distribution and subrogation.


Infliximab Maintenance Dosing in Inflammatory Bowel Disease: an Example for In Silico Assessment of Adaptive Dosing Strategies.
Infliximab is an anti-tumour necrosis factor alpha monoclonal antibody used to treat inflammatory diseases. Many patients fail during induction and others respond initially but relapse during maintenance therapy. Although anti-drug antibodies (ADA) are associated with some clinical failures, there is evidence that some failures may be due to subtherapeutic exposure. Adapting doses based on clinical outcomes and trough concentrations can improve response and reduce the proportion that develop ADA, but identification of appropriate doses in the presence of time-varying patient factors is complicated. Several adaptive dosing strategies (label recommendations versus therapeutic drug monitoring with an established stepwise algorithm or proportional dose adjustments or Bayesian population pharmacokinetic model-based dosing) were simulated on a virtual population (constructed with time-varying covariates and random effects on individual pharmacokinetic parameters) using R to assess their relative performance. Strategies were evaluated on their ability to maintain trough infliximab concentrations above an established target, 3 mg/L, during maintenance phase. Model-based dosing was superior in maintaining target trough concentrations, showing individuals in maintenance achieving concentrations above the target faster and a lower proportion of individuals who developed ADA. Model-based dosing results were consistent across a range of baseline covariate groups. This in silico assessment of adaptive dosing strategies demonstrated that, when challenged with dynamic covariate and random effect changes occurring in individual pharmacokinetic parameters, model-based approaches were superior to other strategies. Model-based dosing has not been tested clinically; however, the potential benefits of model-based dosing for infliximab suggest that it should be investigated to reduce subtherapeutic exposure.


Stereotactic body radiation therapy for lung, spine and oligometastatic disease: current evidence and future directions.
Stereotactic body radiation therapy (SBRT) also referred to as stereotactic ablative radiotherapy (SABR), is a technique which has emerged over the past two decades due to improvements in radiation technology. Unlike conventional external beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically delivered in one to eight fractions, is a technique whereby potentially ablative doses of radiotherapy (usually 7.5-20 Gy per fraction) can be delivered with steeper dose gradients and sub millimetre precision, minimising risk to surrounding normal tissues. The potential benefits of excellent tumor control with low toxicity has led to the increasing use of SBRT in a number of clinical situations. Due to compelling evidence, SBRT is now the treatment of choice for medically inoperable patients with peripherally located stage I non-small cell lung cancer (NSCLC). Controversy remains however as to its efficacy and safety for central or ultra-central lung tumors. The evidence base supporting the use of SBRT as a novel treatment for spinal metastases and oligometastases is rapidly expanding but challenges remain in these difficult patient populations. In an era where targeted therapy and improved systemic treatments for stage IV cancer have resulted in increased disease-free survival, and our knowledge of the oligometastatic state is ever expanding, using SBRT to treat metastatic disease and gain durable local control is increasingly desirable. Several randomized trials are currently underway and are sure to provide valuable information on the benefit and utility of SBRT across many tumor sites including early-stage NSCLC, spinal metastases and oligometastatic disease. Recognizing the evolving role of SBRT in clinical practice, this paper provides a critical review of recent developments in each of these areas particularly highlighting the challenges facing clinicians and discusses potential areas for future research.


Enabling large-scale ground-truth acquisition and system evaluation in wireless health.
Large-scale activity monitoring is a core component of systems aiming to improve our ability to manage fitness, deliver care, and diagnose conditions. While much research has been devoted to the accurate classification of motion, the challenges arising from scaling to large communities have received little attention. This paper introduces the problem of scaling, and addresses two of the most important issues: enabling robust large-scale ground-truth acquisition and building a common database for systems comparison. This paper presents a voice powered mobile acquisition system with efficient annotation tools and an extendable online searchable activity database with 331 datasets totaling over 700 h with 8 sensing modalities and 15 activities.


DNMT3A mutations in Chinese childhood acute myeloid leukemia.
DNA methyltransferase 3A (DNMT3A) mutations have been found in approximately 20% of adult acute myeloid leukemia (AML) patients and in 0% to 1.4% of children with AML, and the hotspots of mutations are mainly located in the catalytic methyltransferase domain, hereinto, mutation R882 accounts for 60%. Although the negative effect of DNMT3A on treatment outcome is well known, the prognostic significance of other DNMT3A mutations in AML is still unclear. Here, we tried to determine the incidence and prognostic significance of DNMT3A mutations in a large cohort in Chinese childhood AML. We detected the mutations in DNMT3A exon 23 by polymerase chain reaction and direct sequencing in 342 children with AML (0-16 years old) from January 2005 to June 2013, treated on BCH-2003 AML protocol. The correlation of DNMT3A mutations with clinical characteristics, fusion genes, other molecular anomalies (FLT3 internal tandem duplication [FLT3-ITD], Nucleophosmin 1, C-KIT (KIT proto-oncogene receptor tyrosine kinase), and Wilms tumor 1 mutations), and treatment outcome were analyzed. DNMT3A mutations were detected in 4 out of 342 (1.2%) patients. Two patients were PML-RARA positive and 1 patient was FLT3-ITD positive. The mutations in coding sequences included S892S, V912A, R885G, and Q886R. Furthermore, there was 1 intronic mutation (c.2739+55A>C) found in 1 patient. No association of DNMT3A mutations with common clinical features was found. Two patients with DNMT3A mutations died of relapse or complications during treatment. One patient gave up treatment due to remission induction failure in day 33. Only 1 patient achieved continuous complete remission. DNMT3A mutations were rare in Chinese children with AML including PML-RARA positive APL. The mutation positions were different from the hotspots reported in adult AML. DNMT3A mutations may have adverse impact on prognosis of children with AML.


Rapid and repeated blood sampling in the conscious laboratory rat: a new technique.
A method for obtaining repeated blood samples from conscious rats by translumbar vena cava puncture is presented. Studies performed at laparotomy enabled us to select a 5/8-in., 25-gauge needle as the ideal instrument for aspirating blood. The awake rat is held prone by an assistant and the needle inserted at the level of the first lumbar vertebra in the coronal plane at an angle of 45 degrees from the vertical. We performed the procedure 350 times in 30 rats (100-300 g) at weekly intervals for 8 wk. Each time, we have obtained 2 ml of blood. The time required for obtaining 30 samples is 15-20 min. There have been no complications and only three deaths (mortality rate, 0.9% per puncture); in all three instances the rats jerked free, lacerating the vena cava. The procedure has been performed in guinea pigs and hamsters, with equal ease, without morbidity or mortality. This new technique permits rapid, atraumatic, repeated samplings from awake animals with no morbidity and minimal mortality.


Patient adherence to generic versus brand statin therapy after acute myocardial infarction: Insights from the Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry.
Statins reduce mortality after acute myocardial infarction, but up to half of patients discontinue statin use within 1 year of therapy initiation. Although cost may influence medication adherence, it is unknown whether use of generic versus brand statins influences adherence. We linked detailed inhospital clinical data for 1421 non-ST-segment elevation myocardial infarction patients discharged on a statin in 2006 to Medicare Part D medication claims records to examine postdischarge medication use. One-year statin adherence was defined using the proportion of days covered with optimal adherence ≥80%. We examined the association of brand versus generic statin prescription and 1-year adherence after adjusting for demographics, clinical factors, predischarge lipid values, prior statin use, and socioeconomic status. Overall, 65.5% of statin fills were for brand-name statins. There were few baseline differences in demographics and clinical factors among generic versus brand users. Patient copay amounts were higher for brand versus generic statins (median = $25 vs $5, P < .001), yet the mean proportion of days covered over 1 year was similar (71.5% vs 68.9%; P = .97; unadjusted odds ratio 1.15 [95% CI 0.96-1.37]). Proportion of days covered ≥80% was low for both generic (56.2%) and brand statins (55.9%; P = .93). Statin adherence rates remained similar between generic and brand users after adjusting for demographics, clinical risk factors, lipid value, prior statin use, and socioeconomic status. In a cohort of older non-ST-segment elevation myocardial infarction patients, we found no evidence that use of generic versus brand drug was associated with higher adherence to statins at 1 year after hospital discharge.


Selective vulnerability of neural cells to viral infections.
A number of viruses selectively infect neurons and, in some cases, specific populations of neurons. The susceptible neuron need not be permissively infected to cause acute or chronic disease; therefore, infectious virus may not be recoverable and morphologically identifiable viral structures may not be detectable by ultrastructural structures. Polioviruses and the neurotropic murine retrovirus both cause paralytic disease with major pathological changes in motor neurons of the spinal cord. Both produce disease more readily in later life; in poliovirus because the mature animals are more susceptible to acute infection, and in the neurotropic retrovirus infections because of the long incubation period of the natural infection. In the acute inflammatory poliovirus infections, the motor neurons appear to be selectively infected and lysed by the virus, whereas in the chronic noninflammatory retrovirus infection, the effect may be indirect or may result from nonpermissive infection.


Bone health in disorders of sex differentiation.
Sex steroids are main regulators of skeletal growth, maturation and mass in both men and women. People with disorders of sex development (DSD) may experience problems in developing normal bone growth, structure and mass, because abnormal sex steroid secretion or action may be operative. In complete androgen insensitivity syndrome several reports documented reduced bone mineral density (BMD). Reduced BMD is evident in patients with not removed or removed gonads, but it is poorer in the latter, mainly when compliance with estrogen replacement therapy is not guaranteed. Large impairment of BMD does not seem to be present in patients with partial androgen insensitivity syndrome or 5alpha-reductase-2 deficiency, providing that gonads are not removed or that substitutive therapy is optimized. In congenital adrenal hyperplasia, BMD may be impaired as a result of not optimal glucocorticoid administration. In Turner syndrome, impaired BMD may result from the combined actions of estrogen deficiency, low bone dimensions, altered bone geometry, deficient cortical bone, and trabecular bone loss. Optimal estrogen administration seems to be important in preserving bone mass and enhancing trabecular bone volume. On the whole, bone health represents a main clinical issue for the management of persons with disorders of sex differentiation, and well designed longitudinal studies should be developed to improve their bone health and well-being.


Disease screening of three breeding populations of adult exhibition budgerigars (Melopsittacus undulatus) in New Zealand reveals a high prevalence of a novel polyomavirus and avian malaria infection.
Disease surveillance is vital to the management of New Zealand's endemic and threatened avian species. Three infectious agents that are potential threats to New Zealand's endemic birds include avian polyomavirus (APV), beak and feather disease virus (BFDV), and avian malaria. All three agents have been reported in New Zealand; however, possible reservoir populations have not been identified. In this communication, we report the first study of APV, BFDV, and avian malaria in introduced adult exhibition budgerigars (Melopsittacus undulatus) in New Zealand. Blood samples were collected from 90 living adult budgerigars from three breeding locations in the North Island of New Zealand. An overall APV prevalence of 22% was determined using a broad-spectrum nested PCR that amplified the major capsid protein VP1 gene of polyomavirus. Phylogenetic analysis of the VP1 gene revealed a unique isolate of APV, which had a sequence divergence of 32% to previously reported budgerigar fledgling disease strains and 33% to the recently reported New Zealand finch isolate. All of the budgerigars sampled were found to be PCR negative for BFDV, and an overall prevalence of 30% was detected by PCR for avian malaria. Sequencing revealed the presence of ubiquitous malarial strains and also the potentially destructive Plasmodium relictum strain. The results of this study suggest that both APV and avian malaria are present in New Zealand adult budgerigars, and our study highlights the need for further studies to determine whether these pathogens in captive bird populations may be a threat or spill over into New Zealand's endemic and threatened avifauna and whether prevention and control methods need to be implemented.


Homology modeling of Kv1.5 channel block by cationic and electroneutral ligands.
The inner pore of potassium channels is targeted by many ligands of intriguingly different chemical structures. Previous studies revealed common and diverse characteristics of action of ligands including cooperativity of ligand binding, voltage- and use-dependencies, and patterns of ligand-sensing residues. Not all these data are rationalized in published models of ligand-channel complexes. Here we have used energy calculations with experimentally defined constraints to dock flecainide, ICAGEN-4, benzocaine, vernakalant, and AVE0118 into the inner pore of Kv1.5 channel. We arrived at ligand-binding models that suggest possible explanations for different values of the Hill coefficient, different voltage dependencies of ligands action, and effects of mutations of residues in subunit interfaces. Two concepts were crucial to build the models. First, the inner-pore block of a potassium channel requires a cationic "blocking particle". A ligand, which lacks a positively charged group, blocks the channel in a complex with a permeant ion. Second, hydrophobic moieties of a flexible ligand have a tendency to bind in hydrophobic subunit interfaces.


Enzyme immunoassay and Scatchard plot estimation of estrogen receptor in gynecological tumors.
Tissue samples of three endometrial carcinomas, seven ovarian carcinomas, and 24 mammary carcinomas were analyzed for estrogen receptor (ER) by enzyme immunoassay (EIA) and a conventional dextran-coated charcoal (DCC) method. In addition, ER and progesterone receptor were assayed by DCC only in 68 ovarian carcinoma specimens. All three endometrial cancer specimens showed elevated ER values by both assays. As with mammary cancers the ER-EIA values tend to be higher than DCC values. It was intriguing to note that negative Scatchard plot data resulted in residual ER levels in the EIA system. Also four ovarian cancer specimens with negative ER values by the DCC assay had detectable levels by ER-EIA, and three of these four had ER-EIA values less than or equal to 10 fmol/mg of protein. Of the ten breast cancers with negative DCC values, seven were less than or equal to 10 fmol/mg of protein by the ER-EIA. Good correlation (r = 0.88) between EIA and Scatchard plot data was calculated from ER data of 24 mammary carcinoma tissue samples. Receptor assays in 68 ovarian cancer patients indicate that ER determinations should become a useful tool in the management of patients bearing this carcinoma. In addition, receptor determinations may improve the possibility of predicting which well differentiated Stage I ovarian carcinomas are likely to recur. Present data combine to suggest that ER-EIA may become a useful diagnostic laboratory tool.


Non-Infectious Diseases Compatible With COVID-19 Pneumonia.
While the definitive diagnosis of the coronavirus disease 19 (COVID-19) is mainly made by the polymerase chain reaction (PCR), some PCR-negative cases are diagnosed typically by a computed tomography (CT) scan's radiology. However, there are many different infectious and non-infectious diseases that have radiology like COVID-19. We are presenting a case of a patient having symptoms and a CT scan radiology comparable to that of COVID-19 and also having eosinophilia. The patient was initially diagnosed and treated as a COVID-19 patient. The patient stated that she had always complained of having dyspnea and cough, but it had increased even more in the past few days. Her thorax CT revealed bilateral ground-glass opacities with upper lobe predominance, which was reported as highly compatible with COVID-19 by radiologists. COVID-19 PCR result was negative twice. In laboratory results, eosinophil count was 2,850/mm3 and total Ig was 768 IU/mL. However, when the laboratory values and the radiological findings were combined with the patient's history, COVID-19 was excluded and the chronic eosinophilic pneumonia was accepted as a diagnosis. Clinicians more focused on COVID-19 while questioning the patients and while evaluating the laboratory and the radiological findings make it easier to miss other infectious and non-infectious diseases. Assessing the complete blood count result, focusing on the lymphocyte value, also makes it easy to skip eosinophilia.


Special Supplemental Nutrition Program for Women, Infants, and Children (WIC): bloodwork requirements. Food and Nutrition Service, USDA. Final rule.
This final rule amends regulations governing the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) to allow State agencies the option to defer the collection of blood test data for up to 90 days after the date of certification, so long as the applicant is determined to have at least one qualifying nutrition risk factor at the time of certification. In addition, this final rule will expand the current regulatory standard of the maximum age of blood test data used to assess nutritional risk for WIC certification. Although blood tests may no longer be a mandatory part of each WIC applicant's certification intake process, such tests are still required for the purposes of assessing nutritional status, nutrition surveillance, providing nutrition education, further tailoring food packages to meet nutritional needs, and referring to appropriate health and social services in the community.


Methamphetamine disposition in oral fluid, plasma, and urine.
This review of the disposition of methamphetamine in oral fluid, plasma, and urine is based on a comprehensive controlled dosing study involving five healthy, drug-free research volunteers who resided on a closed clinical ward for 12 weeks. Subjects were administered four low (10 mg) and high (20 mg) daily oral doses of methamphetamine in two separate sessions. Near-simultaneous collections of oral fluid and plasma were performed on the first day of each low- and high-dose session. Thereafter, oral fluid was provided on each day of dosing by different oral fluid collection methods. All urine specimens were collected on an ad libitum basis throughout the study. Specimens were analyzed by gas-chromatography mass spectrometry for methamphetamine and the metabolite, amphetamine, with a limit of quantification of 2.5 ng/mL for each analyte. Methamphetamine and metabolite concentrations in oral fluid appeared to follow a similar time course in oral fluid as in plasma and were dose-proportional, but oral fluid concentrations exceeded plasma concentrations. Urine drug concentrations were substantially higher than those in oral fluid. Some drug accumulation was noted with daily dosing, but generally did not markedly influence detection times or detection rates of oral fluid tests. Detection times and detection rates for oral fluid and urine were determined at cessation of 4 days of dosing. Generally, detection times and rates for urine were longer than those observed for oral fluid at conventional cutoff concentrations. When contemplating selection of oral fluid as a test matrix, the advantages of oral fluid collection should be weighed against its shorter time of detection compared to that of urine.


DNA damage response and apoptosis.
A number of methods have been developed to examine the morphologic, biochemical, and molecular changes that happen during the DNA damage response that may ultimately lead to death of cells through various mechanisms that include apoptosis. When cells are exposed to ionizing radiation or chemical DNA-damaging agents, double-stranded DNA breaks (DSB) are generated that rapidly result in the phosphorylation of histone variant H2AX. Because phosphorylation of H2AX at Ser 139 correlates well with each DSB, phospho-H2AX is a sensitive marker to used to examine the DNA damage and its repair. Apoptotic cells are characterized on the basis of their reduced DNA content and morphologic changes, including nuclear condensation, which can be detected by flow cytometry (sub-G1 DNA content), trypan blue, or Hoechst staining. The appearance of phosphatidylserine on the plasma membrane with annexin V-fluorochrome conjugates indicates the changes in plasma membrane composition and function. By combining it with propidium iodide staining, this method can also be used to distinguish early versus late apoptotic or necrotic events. The activation of caspases is another well-known biochemical marker of apoptosis. Finally, the Bcl-2 family of proteins and the mitochondria that play a critical role in DNA damage-induced apoptosis can be examined by translocation of Bax and cytochrome c in and out of mitochondria. In this chapter, we discuss the most commonly used techniques used in our laboratory for determining the DNA damage response leading to apoptosis.


A retrospective study on 69 cases of maxillary tooth transposition.
The published literature on tooth transposition includes only a few studies that have involved more than 50 subjects. The aim of the present study was to investigate the prevalence of true maxillary tooth transposition and possible associated dental anomalies in a larger sample of children. The dental records and radiographs of children who had been diagnosed as having true maxillary tooth transposition at a School Dental Clinic in Hong Kong were studied retrospectively. Data were analyzed for sex and side distribution, as well as for associated dental anomalies. Trends of differences were analyzed statistically using the Fisher exact or chi-squared test. A total of 69 cases of true maxillary tooth transposition were identified and studied; its prevalence in Hong Kong Chinese children was 0.81%. More females than males were affected, and the difference between the sexes was statistically significant (P < 0.05). The prevalence of congenitally missing teeth, microdontia of the maxillary lateral incisors or dental impaction was higher in patients with maxillary tooth transposition than in the general population (P < 0.05, P < 0.0005, and P < 0.0001, respectively). The fact that patients with maxillary tooth transposition were more likely to have congenital absence or microdontia of the maxillary lateral incisors lent further support to the contention that a developmental field defect plays a role in the pathogenesis of maxillary tooth transposition.


A total-evidence phylogeny of the lady fern genus Athyrium Roth (Athyriaceae) with a new infrageneric classification.
The lady fern genus Athyrium represents one of the most diversified lineages in Athyriaceae with about 160-220 known species, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies involving this genus, it still lacks a modern systematic and taxonomic update using integrative analyses of molecular and morphological evidence based on a broad species sampling. Here, we present, to our knowledge, the most comprehensive phylogenetic analysis of the genus to date based on a total-evidence approach, covering all formerly accepted segregates within the athyrioid ferns. We sampled up to eight plastid markers and 20 morphological characters for each species. Our analyses, including maximum parsimony, maximum likelihood and Bayesian inference, yield a robust phylogenetic framework. We find that Athyrium is not monophyletic by recovering Athyrium skinneri and A. alpestre nested with Anisocampium and Cornopteris respectively while Pseudocystopteris is included in Athyrium. Furthermore, eight well-resolved clades and two isolated species within Athyrium are found in the phylogenetic topology, which can be also characterized by morphological synapomorphies from traits of petioles, leaves, sori and spores. In the interest of recognizing monophyletic taxa with morphological synapomorphies, we agree with the inclusion of Pseudocystopteris in Athyrium as proposed in previous studies, but treat Anisocampium and Cornopteris as separate genera. We further propose to resurrect a monotypic Pseudathyrium to accommodate A. alpestre. Based on morphological characters and molecular phylogeny, a new infrageneric classification system of Athyrium is proposed which subdivided it into ten sections, and one New-World species A. skinneri is transferred into Anisocampium.