Risk factors for post-COVID cognitive dysfunctions: the impact of psychosocial vulnerability.
Cognitive dysfunction is a well-established manifestation of the post-COVID syndrome. Psychological vulnerability to stressors can modify disease trajectories, causing long-term risk for negative outcomes. Nonetheless, how premorbid risk factors and response to stressor affect neuropsychological changes is still incompletely understood. In this study, we explored the impact of psychosocial variables on cognitive functioning in a post-COVID sample. All subjects were submitted to a comprehensive neuropsychological battery and an assessment of perceived loneliness, post-traumatic stress, and changes in anxiety and depression levels. A social vulnerability index was also calculated. The set of psycho-social variables was reduced to two Principal Component Analysis (PCA) components: distress and isolation. Forty-five percent of individuals showed cognitive impairments, with predominant memory and executive deficits. Post-traumatic stress disorder was clinically relevant in 44% of the sample. Social vulnerability scores of the sample were comparable to those of general population. The individual performance in learning and response initiation/suppression was directly related to distress component, encasing anxiety, stress, and depression measures. These findings suggest that psychosocial assessment of post-COVID patients can detect fragile individuals at risk of cognitive impairments. Dedicated psychological support services may play a useful role in the prevention of post-COVID cognitive dysfunction.


Monoclonal antibodies directed to the blood group A associated structure, galactosyl-A: specificity and relation to the Thomsen-Friedenreich antigen.
Two monoclonal antibodies, HH8 and HH9, have been established after immunization of mice with galactosyl-A glycolipid antigen having the terminal structure, Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----R, which is the precursor for type 3 chain A (repetitive A) and type 3 chain H (A-associated H). Both antibodies react strongly and specifically with galactosyl-A, but HH8 (IgM) showed strong hemagglutination of blood group A1, A2, O and B erythrocytes after sialidase treatment, while HH9 (IgG1) did not react with human erythrocytes even after sialidase treatment. HH8 and anti-T antibody, but not HH9, reacted with glycophorin A after sialidase treatment. The reactivity of HH8 with glycophorin A was abolished by beta-galactosidase and was inhibited by liposomes containing galactosyl-A, but not other glycolipids. In addition, anti-T antibody and peanut lectin reacted specifically with galactosyl-A glycolipids. These findings indicate that HH8 recognizes the terminal disaccharide Gal beta 1----3GalNAc alpha 1----R, which is the same sequence as the classically known Thomsen-Friedenreich antigen (T-antigen), whereas HH9 does not cross-react with T-antigen but recognizes the entire galactosyl-A structure. The T-antigen was also demonstrated by immunohistology with HH8 after neuraminidase treatment in a subset of cells in stratified epithelium.


[Neurotrophic ulcerations in the area of the trigeminal nerve in Wallenberg's syndrome].
We report two new cases of neurotrophic ulceration of the trigeminal nerve associated with Wallenberg syndrome, and we present the six cases published since the first description of the neurologic syndrome, in 1895. This peculiar etiology supports the argument for the dominant physiopathologic hypothesis: ulcerations due to multiple microtraumatisms caused by the thermoalgic anesthesia.


Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.
Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation.


Patients' perspective on choosing the emergency department for nonurgent medical care: a qualitative study exploring one reason for overcrowding.
For decades it has been known that patients use emergency departments for nonurgent care needs. This study was conducted to help determine how the health care community can assist patients achieve consistent health care while meeting the patient's perceived needs. A descriptive qualitative study was conducted based on interviews with 31 persons between 22 and 43 years of age following an ED visit for a nonurgent medical need. Exploration of the patient's perception was accomplished through open-ended questions in a structured interview format. Data were analyzed using content analysis. Patients who participated in our study revealed 3 major themes: (1) They were unable to obtain an appointment with a primary care provider (PCP); (2) they were referred by the staff (not the doctor) in PCPs' offices to be evaluated in the emergency department; and (3) it took less of their time to be seen in the emergency department than it did to contact their PCP, only to then be told to go to the emergency department. The findings of this study support the need for health care providers to find ways to provide nonurgent care in a timely and efficient manner. Multiple options for providing this care need to be conceived and evaluated.


Liver Regeneration Induced By Extracorporeal Portal Vein Arterialization in a Swine Model of Carbon Tetrachloride Intoxication.
This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced in swine by carbon tetrachloride (CCl4) administration. Sixteen swine with AHF induced by intraperitoneal injection of CCl4 in oil solution were randomly divided into 2 groups: animals that received L.E.O2 NARDO treatment 48 hours after the intoxication (study group; n = 8); and animals that were sham operated 48 hours after the intoxication (control group; n = 8). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 hours. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different study time and liver biopsies were performed 48 hours after intoxication and at humane killing. In the study group decreased transaminases levels and a more rapid international normalized ratio (INR) recover were detected as compared with the control group. Six animals of the study group (75%) versus 1 animal (12.5%) of the control group survived at 5 days after surgery with a statistically significant difference (P < .05). Liver biopsies performed at humane killing showed damaged areas of the livers reduced in the study group compared with biopsies of the control group. Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.


An aggressive form of familial amyloid polyneuropathy caused by a Glu54Gly mutation in the transthyretin gene.
We report a patient with familial amyloid polyneuropathy. Gene analysis revealed a heterozygous Glu54Gly substitution (A-to-G change) in the transthyretin gene. This is the first case of a Glu54Gly substitution that was devoid of a Gly6Ser substitution. Compared with the previously reported case with compound heterozygotes of Glu54Gly and Gly6Ser, the age of onset in our case is much younger and another characteristic findings were the amyloid vasculopathy and the multiple organ involvement. A Glu54Gly mutation is amyloidogenic by itself and a Gly6Ser mutation may offer some protection from the Glu54Gly mutant.


MiR-142-3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer.
MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.


Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison.
The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.


Population dynamics with spatial structure and an Allee effect.
Population dynamics including a strong Allee effect describe the situation where long-term population survival or extinction depends on the initial population density. A simple mathematical model of an Allee effect is one where initial densities below the threshold lead to extinction, whereas initial densities above the threshold lead to survival. Mean-field models of population dynamics neglect spatial structure that can arise through short-range interactions, such as competition and dispersal. The influence of non-mean-field effects has not been studied in the presence of an Allee effect. To address this, we develop an individual-based model that incorporates both short-range interactions and an Allee effect. To explore the role of spatial structure we derive a mathematically tractable continuum approximation of the IBM in terms of the dynamics of spatial moments. In the limit of long-range interactions where the mean-field approximation holds, our modelling framework recovers the mean-field Allee threshold. We show that the Allee threshold is sensitive to spatial structure neglected by mean-field models. For example, there are cases where the mean-field model predicts extinction but the population actually survives. Through simulations we show that our new spatial moment dynamics model accurately captures the modified Allee threshold in the presence of spatial structure.


Exploring the mitochondrial proteome of the ciliate protozoon Tetrahymena thermophila: direct analysis by tandem mass spectrometry.
To date, direct analysis of mitochondrial proteomes has largely been limited to animals, fungi and plants. To broaden our knowledge of mitochondrial structure and function, and to provide additional insight into the evolution of this key eukaryotic organelle, we have undertaken the first comprehensive analysis of the mitochondrial proteome of a protist. Highly purified mitochondria from Tetrahymena thermophila, a ciliated protozoon, were digested exhaustively with trypsin and the resulting peptides subjected to tandem liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS). In this way, we directly identified a total of 573 mitochondrial proteins, 545 of which are encoded by the nuclear genome and 28 by the mitochondrial genome. The latter number includes a novel, 44 residue protein (which we designate Ymf78) that had not been recognized during annotation of the T. thermophila mtDNA sequence. The corresponding gene, ymf78, is highly conserved in genomic position, size and sequence within the genus Tetrahymena. Our analysis has provided broad coverage of both membrane-bound and soluble proteins from the various submitochondrial compartments, with prominent representatives including components of the tricarboxylic acid cycle, Complexes I-IV of the electron transport chain and Complex V (ATP synthase), the mitochondrial transcription and translation machinery, the TOM and TIM protein translocases, various mitochondrial transporters, chaperonins (Cpn60, Hsp70, Hsp90), at least four FtsH family ATP-dependent metalloproteases implicated in m-AAA and i-AAA protease function, and enzymes involved in lipid, amino acid and coenzyme metabolism, as well as iron-sulfur cluster formation. Unexpectedly, six of the ten enzymes of glycolysis were found by MS analysis of purified T. thermophila mitochondria, whereas no hits were seen to any cytosolic ribosomal proteins. At least one of the glycolytic proteins, enolase, has an evident N-terminal extension that exhibits characteristics of a typical mitochondrial targeting peptide. As in other organisms, phylogenetic analysis of functionally annotated mitochondrial proteins demonstrates that <20% can be traced confidently to the alpha-proteobacterial lineage of Bacteria, emphasizing the chimeric evolutionary nature of the mitochondrial proteome. Notably, about 45% of the proteins identified in our analysis have no known function, and most of these do not have obvious homologs outside of the ciliate lineage. About two-thirds of these ORFan proteins have putative homologs in another ciliate, Paramecium tetraurelia, whereas the remainder appear to be Tetrahymena-specific. These results emphasize the power and importance of direct MS-based analysis of mitochondria in revealing novel mitochondrial proteins in different eukaryotic lineages. Our observations reinforce an emerging view of the mitochondrion as an evolutionarily flexible organelle, with novel proteins (and presumably functions) being added in a lineage-specific fashion to an ancient, highly conserved functional core, much of which was contributed by the presumptive alpha-proteobacterial symbiont from which the mitochondrial genome was derived.


Impact of roadside features on the frequency and severity of run-off-roadway accidents: an empirical analysis.
In the US, single-vehicle run-off-roadway accidents result in a million highway crashes with roadside features every year and account for approximately one third of all highway fatalities. Despite the number and severity of run-off-roadway accidents, quantification of the effect of possible countermeasures has been surprisingly limited due to the absence of data (particularly data on roadside features) needed to rigorously analyze factors affecting the frequency and severity of run-off-roadway accidents. This study provides some initial insight into this important problem by combining a number of databases, including a detailed database on roadside features, to analyze run-off-roadway accidents on a 96.6-km section of highway in Washington State. Using zero-inflated count models and nested logit models, statistical models of accident frequency and severity are estimated and the findings isolate a wide range of factors that significantly influence the frequency and severity of run-off-roadway accidents. The marginal effects of these factors are computed to provide an indication on the effectiveness of potential countermeasures. The findings show significant promise in applying new methodological approaches to run-off-roadway accident analysis.


Fipronil and 2,4-D effects on tropical fish: Could avoidance response be explained by changes in swimming behavior and neurotransmission impairments?
Brazil is the largest producer of sugarcane, a crop largely dependent on chemical control for its maintenance. The insecticide fipronil and herbicide 2,4-D stand out among the most commonly used pesticides and, therefore, environmental consequences are a matter of concern. The present study aimed to investigate the toxicity mechanisms of Regent® 800 WG (a.i. fipronil) and DMA® 806 BR (a.i. 2,4-D) pesticides using forced and non-forced exposures through an integrative approach: firstly, to assess whether contamination by fipronil and 2,4-D can trigger the avoidance behavior of the fish Danio rerio (zebrafish) and Hyphessobrycon eques (serpae tetra or mato-grosso). Additionally, the effects on fish were analyzed considering the swimming behavior together with a biomarker of neurotoxicity, the activity of acetylcholinesterase (AChE). In avoidance tests with pesticide gradients, D. rerio avoided the highest concentrations of the two compounds and H. eques avoided only the highest concentration of 2,4-D. The swimming behavior (distance moved) was reduced and AChE was inhibited when D. rerio was exposed to fipronil. The 2,4-D affected the swimming (maximum speed) of H. eques, but AChE was not altered. Avoidance response seemed not to have been affected by possible effects of contaminants on swimming behavior and Ache activity. This study showed the importance of knowing the avoidance capacity, swimming behavior and neurotoxic effects of pesticides on fish in an integrated and realistic context of exposure in environments contaminated with pesticides and can be useful as ecologically relevant tools for ecological risk assessment.


Draft Whole-Genome Sequences for Two Pigmentiphaga Isolates Recovered from Human Clinical Materials.
Features from two Pigmentiphaga isolates referred to Canada's National Microbiology Laboratory from human clinical materials were described previously (N. Bridger, S. Drews, T. Burdz, D. Wiebe, A. L. Pacheco, B. Ng, and K. Bernard, J Med Microbiol 62:708-711, 2013, https://doi.org/10.1099/jmm.0.051615-0). Whole-genome sequencing was performed on strains NML030171 and NML080357; the sequences were found to have 5.86 and 5.73 Mb of clean data and G+C contents of 67.5 and 66.74 mol%, respectively.


Chemical and biological properties of indole glucosinolates (glucobrassicins): a review.
Glucosinolates are a group of secondary products commonly, but not exclusively, found in plants of the family Cruciferae. They give rise, upon enzymic hydrolysis, to a range of volatile, pungent and physiologically active compounds. Recently, particular attention has been focused upon those that are trytophan-derived--the indole glucosinolates (glucobrassicins). When chemically or enzymically hydrolysed these compounds give rise to a range of involatile indole compounds which have been implicated in the anti-carcinogenic and mixed-function-oxidase stimulatory activities of brassica vegetables. This review details the chemical and physiological properties of indole glucosinolates and their products and suggests possible areas for future research.


Pericardial hemangiopericytoma as a cause of dysphagia.
A 68-year-old woman was seen with recent-onset dysphagia. Investigations suggested a large retrocardiac tumor. At thoracotomy, a highly vascular tumor was found, involving the posterior and left aspect of the pericardium with attachment to the heart. The lesion was partially removed, and histopathological analysis revealed a malignant hemangiopericytoma. To our knowledge, this tumor site and its presentation have not been reported before.


Exploratory study on application of MALDI‑TOF‑MS to detect serum and urine peptides related to small cell lung carcinoma.
Matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF‑MS) was employed to analyze differential serum and urine peptides in patients with small cell lung cancer (SCLC) and healthy individuals, and SCLC diagnostic classification models were constructed. Serum and urine samples from 72 patients with SCLC, age‑ and gender‑matched with 72 healthy individuals, were divided into training and testing sets in a 3:1 ratio. Serum and urine peptides were extracted using copper ion‑chelating nanomagnetic beads, and mass spectra were obtained using MALDI‑TOF‑MS. Peptide spectra for the training set were analyzed, and the classification model was constructed using ClinProTools (CPT). The testing set was used for blinded model validation. For training‑set sera, 122 differential peptide signal peaks with a mass of 0.8‑10 kDa were observed, and 19 peptides showed significantly different expression [P<0.0005; area under curve (AUC) ≥0.80]. CPT screened 5 peptide peaks (0.8114, 0.83425, 1.86655, 4.11133 and 5.81192 kDa) to construct the classification model. The testing set was used for the blinded validation, which had 95.0% sensitivity and 90.0% specificity. For the training‑set urine, 132 differential peptide signal peaks with m/z ratios of 0.8‑10 kDa were observed, and 8 peptides had significantly different expression (P<0.0005; AUC ≥0.80). Then, 5 peaks (1.0724, 2.37692, 2.7554, 4.75475 and 4.7949 kDa) were used for classification model construction. The testing set was used for 36 blinded validation, which had 85.0% sensitivity and 80.0% specificity. Among the differential peptides, 3 had the same significant peaks at 2.3764, 0.8778 and 0.8616 kDa, identified as fibrinogen α, glucose‑6‑phosphate isomerase and cyclin‑dependent kinase‑1, respectively. The present study highlighted the differences that exist in serum and urine peptides between patients with SCLC and healthy individuals. Serum and urine peptide diagnostic classification models could be constructed using MALDI‑TOF‑MS, and showed high sensitivity and specificity.


In vitro antifungal activity of 2-(4-substituted phenyl)-3(2H)-isothiazolones.
The in vitro antifungal activity of several N2-phenyl-3(2H)-isothiazolones substituted at C4 of the phenyl moiety with heterocyclic nucleus or groups of different physico-chemical properties against four human pathogenic fungi was determined by broth macrodilution method; results were compared with those obtained with itraconazole and ketoconazole. These isothiazolones showed moderate to high activity against some or all tested strains and in comparison with the reference drugs, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g), 5-chloro-2-phenylisothiazol-3-one (1c), 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]-1,4-dihydrotriazol-5-one (1s) and 2-(4-nitrophenyl)isothiazol-3-one (2g) against Aspergillus niger, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g) and 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]piperazine-1-carboxamide (1q) against Trichophyton mentagrophytes had comparable activity, compounds 1g and 2g showing higher activity against Microsporum canis. Antifungal activity was favored by the presence of chlorine at C5 of the isothiazolone and/or the presence of nitro group or heterocyclic nucleus at C4 of the phenyl ring and proper hydrophilicity of the molecule.


ONTOGENY AND THE HIERARCHY OF TYPES.
Abstract- The long history of belief in a parallelism between ontogeny and a hierarchical order of natural things is reviewed. The meaning of von Baerian recapitulation is analyzed and its implications for cladistic methodology are discussed at two levels: ontogeny and homology. The basic problem inherent in the purported parallelism is that the order of natural things (i.e., the taxic approach to homology) is part of the "world of being" of Platonic ideas, whereas ontogeny and phylogeny (i.e., the transformational approach to homology) belong to Plato's "world of becoming." These two "genera of existence," as Plato put it, being and becoming, are incompatible but complementary views of nature.


The paradox of Ferrata and the fate of the extruded red cell nucleus: two problems concerning erythropoiesis in the human.
A critical analysis of the present erythropoietic pathway reveals two problems which require resolving. One is the paradox of the basophilic erythroblast, and the other is the fate of the extruded red cell nucleus. The problems can be overcome if erythropoiesis is looked at differently, and the orthochromatic normoblast considered to arise directly from a denuded stem cell nucleus as has been previously suggested. The orthochromatic normoblast extrudes its nucleus leaving behind a reticulocyte. The extruded but functionally impaired nucleus of the orthochromatic normoblast then gives rise to a polychromatic normoblast, a defective cell. The poorly made cytoplasm of the polychromatic normoblast is shed and its nucleus, now non-functional, undergoes complete dissolution into an aggregate of ultrafine particles. The theory has the advantage that the fate of the extruded red cell nucleus can be explained without having to introduce phagocytosis by macrophages and all the immunological difficulties which this entails. The new pathway does away with the basophilic erythroblast as a haemoglobin-producing cell, and it is argued that the cell instead is a ferritin storage cell, and that erythropoiesis is the result of two separate but interdependent pathways, a ferritin storage pathway and a haemoglobin production pathway. Evidence is put forward to support the new pathways.


A comparison of proximal tibia, distal femur, and proximal humerus infusion rates using the EZ-IO intraosseous device on the adult swine (Sus scrofa) model.
We sought to compare the flow rates of the proximal tibia, the distal femur, and the proximal humerus using high pressure (greater than 300 mmHg) through an intraosseous (IO) infusion needle in an adult swine model. We performed a prospective interventional study in 11 swine. After placement of central vein and arterial lines, blood was removed via the central line until the animal's mean arterial pressure decreased 25% from the recorded baseline. We inserted a 25-mm IO needle into the proximal tibia and 45-mm needles into the distal femur and proximal humerus. All extremities were utilized in each study animal. We infused normal saline at each site for 10 minutes with a pressure bag inflated to the highest achievable pressure (greater than 300 mmHg) as measured at the infusion site with a calibrated portable inline pressure gauge. We measured the volume of normal saline remaining and we calculated infusion rates for each site. We then compared infusion flow rates between the three locations. Statistical analysis and comparison of the infusion rates of all three study arms were as performed using analysis of variance (ANOVA). The average weight of the swine was 71 kg (range 64-84 kg). Successful placement of the IO needle was confirmed at all three sites. The mean infusion flow rate was 213 mL/min (standard deviation [SD] 53.2 mL/min) for the proximal humerus, 138 mL/min (SD 65.3 mL/min) for the distal femur, and 103 mL/min (SD 48.1 mL/min) for the proximal tibia (p < 0.001). The flow rate through the proximal humerus was statistically greater than that for the proximal tibia and the distal femur (p < 0.001). The flow rates through the proximal tibia and distal femur were similar. The humerus is a suitable alternative site for IO placement, with a potential for higher flow rates than the proximal tibia and distal femur when resuscitating a patient.


Diverse functions of vertebrate gap junctions.
Gap junctions are clusters of intercellular channels between adjacent cells. The channels are formed by the direct apposition of oligomeric transmembrane proteins, permitting the direct exchange of ions and small molecules (< 1 kDa) between cells without involvement of the extracellular space. Vertebrate gap junction channels are composed of oligomers of connexins, an enlarging family of proteins consisting of perhaps > 20 members. This article reviews recent advances in understanding the structure of intercellular channels and describes the diverse functions attributable to gap junctions as a result of insights gained from targeted gene disruptions in mice and genetic disease in humans.


MiR-26a inhibits stem cell-like phenotype and tumor growth of osteosarcoma by targeting Jagged1.
MicroRNAs (miRNAs) are important epigenetic regulators of gene expression. Although several miRNAs have been implicated in osteosarcoma, their role in regulation of osteosarcoma cancer stem cells (CSCs) remains unknown. Here we demonstrated that miR-26a is downregulated in osteosarcoma CSCs when derived by either sarcosphere generation, chemodrug or aldehyde dehydrogenase (ALDH) activity selection. Lentiviral overexpression of miR-26a in ZOS and 143B osteosarcoma cells decreases the expression of stem cell markers and suppresses sarcosphere formation, as well as ALDH activity. Moreover, miR-26a overexpression inhibits the tumor cell growth both in vitro and in vivo. We further demonstrate that miR-26a directly target Jagged1, one of the Notch ligand, and that its tumor suppressive effects are mediated through inhibition of Jagged1/Notch signaling. Importantly, reduced miR-26a expression, as determined by in situ hybridization in patient tumors (n=92), is associated with lung metastasis and poor overall survival of osteosarcoma patients. Together, these data suggest the essential role of miR-26a/Jagged1/Notch pathway in regulating the stem cell-like traits of osteosarcoma cells and provide a potential target for osteosarcoma therapy.


Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP).
Prion diseases are fatal and malignant infectious encephalopathies induced by the pathogenic form of prion protein (PrPSc) originating from benign prion protein (PrPC). A previous study reported that the M132L single nucleotide polymorphism (SNP) of the prion protein gene (PRNP) is associated with susceptibility to chronic wasting disease (CWD) in elk. However, a recent meta-analysis integrated previous studies that did not find an association between the M132L SNP and susceptibility to CWD. Thus, there is controversy about the effect of M132L SNP on susceptibility to CWD. In the present study, we investigated novel risk factors for CWD in elk. We investigated genetic polymorphisms of the PRNP gene by amplicon sequencing and compared genotype, allele, and haplotype frequencies between CWD-positive and CWD-negative elk. In addition, we performed a linkage disequilibrium (LD) analysis by the Haploview version 4.2 program. Furthermore, we evaluated the 3D structure and electrostatic potential of elk prion protein (PrP) according to the S100G SNP using AlphaFold and the Swiss-PdbViewer 4.1 program. Finally, we analyzed the free energy change of elk PrP according to the S100G SNP using I-mutant 3.0 and CUPSAT. We identified 23 novel SNP of the elk PRNP gene in 248 elk. We found a strong association between PRNP SNP and susceptibility to CWD in elk. Among those SNP, S100G is the only non-synonymous SNP. We identified that S100G is predicted to change the electrostatic potential and free energy of elk PrP. To the best of our knowledge, this was the first report of a novel risk factor, the S100G SNP, for CWD.


Ultrasound inflammation imaging in rats with myocardial ischemia-reperfusion: evaluation by non-specific targeted contrast microbubbles.
Reports on ultrasound inflammation imaging with non-specific targeted microbubbles in the heart have been scarce. We investigated whether inflammation induced by myocardial ischemia-reperfusion in rats could be evaluated by ultrasound inflammation imaging with non-specific targeted microbubbles. Six rats subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion (ischemia group) and 4 rats subjected to the sham operation (sham group) were used. Ultrasound inflammation imaging was performed 4 h after reperfusion, and non-circulating signal intensity (SI), which reflects the signal derived from microbubbles phagocytosed by neutrophils in inflamed tissue, was calculated by the SI difference between the initial and subsequent imaging both in the LAD and non-LAD areas. The accumulation of neutrophils was confirmed by myeloperoxidase (MPO) staining. Non-circulating SI in the LAD area was significantly greater for the ischemia group than the sham group [5.19 ± 2.19 (ischemia) vs. 0.31 ± 0.13 (sham) dB, p < 0.01]. Non-circulating SI in the LAD area was significantly higher than that in the non-LAD area when compared in the same rat of the ischemia group [5.19 ± 2.19 (LAD) vs. 0.18 ± 0.64 (non-LAD) dB, p < 0.01]. MPO-positive cells were confirmed in the LAD area of the ischemia group. Inflammation induced by myocardial ischemia-reperfusion in rats could be quantitatively assessed by ultrasound inflammation imaging with non-specific targeted microbubbles.


[Intestinal malrotation with volvulus associated with severe stress hyperglycemia].
A 2-year-old boy was admitted with diagnosis of diabetes debut, with blood glucose of 500 mg% on admission, without ketosis or metabolic acidosis. He also presented bilious vomiting and brownish bloody stools. He was operated with a presumptive diagnosis of acute intestinal obstruction. The final diagnosis was volvulus, secondary to congenital malrotation. After surgery, he normalized blood sugar levels. The clinical setting was assumed as hyperglycemia without ketosis, with characteristic of severity caused by stress, secondary to volvulus in malrotation. This association has not yet been described.


Early markers of endocrinometabolic disease in newborns with delayed intrauterine growth.
The adjustments to malnutrition in growth restricted fetus (GRF) that lead to obesity, insulin resistance, diabetes and cardiovascular disease in adulthood are not well known. The most feasible explanation for this association is the hypothesis of catch up. Some studies postulate a greater influence of catch up growth than the low birth weight itself in developing metabolic and cardiovascular disease. This is a prospective cohort study of newborns with intrauterine growth restriction (defined as weight percentile at birth less than 10th) born during a one-year period. Clinical data of patients were recorded (gender, gestational age, data about breastfeeding and anthropometry during follow-up every 3 months). Some details of pregnancy and characteristics of the mother were also registered. Serum biochemical parameters (IGF-1, IGF-BP3, insulin, glucose, total cholesterol, HDL cholesterol, DLD cholesterol, triglycerides, HOMA) were collected at birth from cord blood, 9 and 12 months. Two main comparative groups were established: those GRF who made a catch-up growth (increase in weight Z score higher than 0,67) during the follow-up and those who did not get it. 126 GRF children were born in the study period. 125 accepted the inclusion in the study and 67 of them completed the full monitoring for a year; 47 of them made recovery growth and 20 did not. A significant difference between both groups was found in glucose in umbilical cord and triglycerides at 12 months: GRF children with catch up growth showed lower glucose levels (p = 0.03) and higher levels of triglycerides (p = 0.03). There were no statistically significant differences in the rest of laboratory parameters analyzed (IGF-1, IGF-BP3, insulin, glucose, total cholesterol, HDL cholesterol, DLD cholesterol, HOMA at 9 and 12 months or triglycerides at 9 months). Those GRF with catch up growth during the first year of life have early changes in the triglycerides at the end of that period with higher levels than those GRF children without catch up growth. This finding could be useful to develop a tool for early detection of GRF children with higher metabolic risk in order to prevent future pathology.


[The measurement of aerosol density of ultrasonic inhalation generators (author's transl)].
Measurements of the behaviour of ultrasonic USI-Nebulizers during operation were carried out using a simple photometric arrangement. It shows, that the electrically controlled feed system of USI 3 and USI 50 is superior to the far simpler chicken feed system of USI 3 and USI 50 is superior to the far simpler chicken feed system. For the inhalation of small amounts of medicament not using the feed system the measuring procedure for the remaining amount of medicament should be reconsidered.


Aphicidal activity of farnesol against the green peach aphid - Myzus persicae.
Myzus persicae (Hemiptera: Aphididae) is considered one of most important agricultural pests in the world. It is one of the main pests in protected pepper crops under glasshouse conditions in Southeastern Spain, but its control is limited as a consequence of the few available authorized insecticides and their incompatibility with the natural enemies. Some essential oils and pure compounds such as anise (Pimpinella anisum) or farnesol are repellent and/or toxic to aphids. Their use as a botanical insecticides can be an alternative for aphid control in pepper. The effect of farnesol was evaluated against M. persicae in a new bioassay developed to test the contact effect (aqueous formulation of the products) on aphids in laboratory conditions. Aniseed essential oil, geraniol and (Z)-jasmone at 0.6% causes an aphid mortality of >50%; and farnesol was the most effective (93.67% mortality). Farnesol nanoemulsions between 0.2% and 0.6% were formulated with an IKA-Labor Pilot dispersing machine (7940 rpm for 10 min) using Tween 80 as a surfactant. These formulations were tested on field experiments (glasshouse conditions) on pepper crops for 2 years. Foliar applications of farnesol at a concentration of 0.4% in field conditions causes a high reduction in aphid populations, with efficacies of ≈70-80% with respect to the control, similar to or even higher than the efficacy of the reference pyrethrin insecticide. Farnesol showed a great aphicidal effect against M. persicae. The use of this molecule in integrated pest management programs combined with natural enemies is a good option for future control of M. persicae. © 2022 Society of Chemical Industry.


Motility is rate-limiting for invasion of bladder carcinoma cell lines.
Induced migration of tumor cells is generally considered to be one critical step in cancer progression to the invasive and metastatic stage. The implicit caveat of studies that show this is that other, unknown, signaling pathways and biophysical events are actually the operative rate-limiting steps, and not motility per se. Thus, to examine the hypothesis that motility is a single, but overall rate-limiting function required for invasion, disparate motility processes need be blocked with concordant effects on tumor invasion. Recently, we and others have described two signaling pathways that are critical to growth factor-induced motility but not mitogenesis. The key molecular switches are phospholipase C-gamma (PLCgamma) and calpain for cytoskeletal reorganization and rear detachment, respectively. We examined this hypothesis in a highly invasive tumor, bladder carcinoma. Three different human tumor cell lines, 253J-B-V, UMUC and T-24, were tested for invasiveness in vitro by transmigration of a Matrigel barrier. Inhibiting PLCgamma with the pharmacologic agent U73122 or the molecular dominant-negative PLCz construct reduced both invasiveness and motility. The same was noted when calpain was blocked using calpain inhibitor I (ALLN). These results demonstrate that one interventional target for limiting invasion is not necessarily an individual motility pathway but rather cell migration per se.


Sonographic follow-up of diaphragm function in COVID-19: an exploratory study.
Survivors of COVID-19 frequently endure chronic disabilities. We hypothesise that diaphragm function has a long recovery time after COVID-19 hospitalisation and may play a role in post-COVID-19 syndrome. The aim of this study was to assess diaphragm function during COVID-19 hospitalisation and during recovery. We conducted a prospective single-centre cohort study in 49 enrolled patients, of which 28 completed 1-year follow-up. Participants were evaluated for diaphragm function. Diaphragm function was assessed using ultrasound measuring of diaphragm thickening fraction (TF) within 24 h after admission, after 7 days of admission or at discharge, whichever came first, and 3 and 12 months after hospital admission. Estimated mean TF increased from 0.56 (95% CI 0.46-0.66) on admission to 0.78 (95% CI 0.65-0.89) at discharge or 7 days after admission, to 1.05 (95% CI 0.83-1.26) 3 months after admission and to 1.54 (95% CI 1.31-1.76) 12 months after admission. The improvements from admission to discharge, 3 months and 12 months were all significant (linear mixed modelling; p=0.020, p<0.001 and p<0.001, respectively), and the improvement from discharge to 3-month follow-up was borderline significant (p<0.1). Diaphragm function was impaired during hospitalisation for COVID-19. During recovery in hospital and up to 1-year follow-up, diaphragm TF improved, suggesting a long recovery time of the diaphragm. Diaphragm ultrasound may be a valuable modality in the screening and follow-up of (post-)COVID-19 patients for diaphragm dysfunction.


Correlation between number of renal cysts and aortic circumferences measured using autopsy material.
Although the presence of renal cysts has been reported to be associated with aortic aneurysm or dissection by imaging studies, an autopsy study has not been performed. Therefore, in our institute, recent consecutive adult autopsy cases (n=108, 64 males and 44 females) were reviewed. The circumferences and atherosclerosis ratios of both thoracic and abdominal aorta were individually measured and graded. The number of renal cysts was scored and graded. Age of subjects along with histories of smoking, hypertension, and diabetes mellitus were confirmed. Multiple linear regression analyses demonstrated that severity of atherosclerosis and the number of renal cysts were correlated with thoracic aortic circumference, while only the number of renal cysts was correlated with abdominal aortic circumference (p<0.05), which was more predominant in female subjects (p<0.05). Microscopically, significantly more dilated renal tubules (by Student's t-test, p<0.05) along with decreased stainability of basement membrane by Periodic acid-Schiff staining and immunostaining of type IV collagen were noted in background renal tissues in cases with numerous renal cysts than in age- and sex-matched controls without renal cysts (n=10 vs. 10). The present study suggests that a syndrome that affects both aorta and renal tubules may exist.


BVA Gala Dinner - a date for your diary.
BVA's 2016 Gala Dinner will be held at the London Marriott Hotel West India Quay on November 17. Here Tim Keen, BVA marketing manager, explains what the evening will involve.


Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube.
Immune cell trafficking and surveillance within the ovary and fallopian tube are thought to impact fertility and also tumorigenesis in those organs. However, little is known of how native cells of the ovary and fallopian tube interact with resident immune cells. Interaction of the Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint with PD-L1 is associated with downregulated immune response. We have begun to address the question of whether PD-1 ligand or its receptors (PD-L1/-L2) can regulate immune cell function in these tissues of the female reproductive tract. PD-1 and ligand protein expression was evaluated in human ovary and fallopian tube specimens, the latter of which included stages of tubal cell transformation and early tumorigenesis. Ovarian expression analysis included the determination of the proteins in human follicular fluid (HFF) specimens collected during in vitro fertilization procedures. Finally, checkpoint bioactivity of HFF was determined by treatment of separately-isolated human T cells and the measurement of interferon gamma (IFNγ). We show that membrane bound and soluble variants of PD-1 and ligands are expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were present in HFF at bioactive levels that control T cell PD-1 activation and IFNγ production; full-length checkpoint proteins were found to be highly enriched in HFF exosome fractions. The detection of PD-1 checkpoint proteins in the human ovary and fallopian tube suggests that the pathway is involved in immunomodulation during folliculogenesis, the window of ovulation, and subsequent egg and embryo immune-privilege. Immunomodulatory action of receptor and ligands in HFF exosomes is suggestive of an acute checkpoint role during ovulation. This is the first study in the role of PD-1 checkpoint proteins in human tubo-ovarian specimens and the first examination of its potential regulatory action in the contexts of normal and assisted reproduction.


Opticin production is reduced by hypoxia and VEGF in human retinal pigment epithelium via MMP-2 activation.
Opticin, a small leucine rich repeat protein (SLRP) contributes to vitreoretinal adhesion. This study was conducted to investigate the effects of hypoxia and vascular endothelial growth factor (VEGF) on matrix metalloproteinase (MMP) mediated opticin production in retinal pigment epithelium (RPE) cells. Primary cultured human RPE cells were treated with hypoxia (low oxygen and cobalt chloride) or VEGF (0-100 ng/mL). The mRNA levels of opticin and the protein levels of intra and extracellular opticin in RPE cells were examined by RT-PCR and Western blot assay, respectively. Furthermore, the MMP activity was analyzed by zymography, and EDTA was used as an MMP inhibitor. Analysis of the effect of MMP-2 on opticin was performed by recombinant human (rh) MMP-2 stimulation in RPE cultures and by human vitreous sample digestion with activated rhMMP-2. Our results showed that opticin was expressed by primary cultured human RPE cells. Hypoxia and VEGF stimulation did not alter opticin mRNA and protein expression in RPE cells, but markedly decreased the protein levels of extracellular opticin following increased latent MMP-2 activity. The VEGF- and hypoxia induced opticin degradation in the culture medium was blocked by EDTA. Together, opticin levels in the culture medium were also reduced after rhMMP-2 treatment. In addition, opticin in human vitreous samples could be cleaved by rhMMP-2. These results reveal that VEGF and hypoxia could decrease opticin protein levels in the human RPE secretome, and that opticin may be an enzymatic substrate for MMP-2.


A simple, feasible, efficient and safe treatment strategy of sofosbuvir/velpatasvir for chronic HCV/HIV-1 coinfected patients regardless of HCV genotypes: a multicenter, open-label study in China.
The direct-acting antiviral agents (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. However, a simple and feasible treatment strategy with high efficacy and safety for HCV in patients coinfected with Human Immunodeficiency Virus (HIV) remains an unmet medical need, especially in areas with limited health resource. This study aims to assess the efficacy and safety of 12 weeks of treatment with sofosbuvir and velpatasvir in patients with chronic HCV/HIV-1 coinfection. We conducted a multicenter, single-arm, open-label study in China, which involved chronic HCV/HIV-1 coinfected patients who are receiving an antiretroviral regimen of a combination tablet consisting of elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, (EVG/c/FTC/TAF) once daily. Patients with liver cirrhosis or experienced to DAAs treatment were excluded. All patients received combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks regardless of HCV genotype. The primary efficacy endpoint was sustained virologic response, defined as HCV RNA <15 IU/mL at 12 weeks after completion of treatment (SVR12). The primary safety endpoint was the proportion of patients who prematurely discontinued treatment because of adverse events. Safety and efficacy data were analyzed with an intention-to-treat (ITT) population (last observation carried forward) and per-protocol (PP) population. This trial is registered on ChiCTR.org.cn with number being ChiCTR1800020246. Of the 243 patients enrolled, 78% were male, 9% had been previously treated for HCV with interferon, and none had pre-defined cirrhosis, although 8% had Fibrosis 4 score (FIB-4) >3.25. A total of 233 patients completed 12-week post-treatment follow-up. Overall, 227/233 patients (97%) achieved SVR12: 100% (63/63) in those with HCV genotype 1, 67% (2/3) in those with genotype 2, 95% (84/88) in those with genotype 3, 99% (78/79) in those with genotype 6. Rates of SVR12 were lower among those with baseline FIB-4 >3.25 than those without (78% [14/18] vs. 99% [211/212], P < 0.001). HIV-1 suppression was not compromised. The most common adverse events were upper respiratory tract infection (5%), cough (3%), abnormal renal function (2%), abnormal liver function (2%), constipation (2%), urinary tract infection (2%) and sleep disorders (2%). No participant discontinued treatment because of adverse events or death. Twelve weeks of treatment with sofosbuvir/velpatasvir provide high rates of SVR and is well-tolerated in patients coinfected with HIV-1 and HCV regardless of HCV genotypes. Non-invasive liver fibrosis score may help to further distinguish patients at greater likelihood of a suboptimal response. The 13th Five Year Plan of the Ministry of Science and Technology of China for the prevention and treatment of major infectious diseases such as AIDS and viral hepatitis, the National Key Research and Development Program of China, Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases (2021-2023), Basic research program on people's Livelihood Science and technology of Guangzhou, and National Natural Science Foundation of China.


Ca2+ and cyclic nucleotide dependence of amylase release from isolated rat pancreatic acinar cells rendered permeable by intense electric fields.
Enzyme digestion of rat pancreatic tissue yielded a preparation of isolated acinar cells, over 90% of which excluded trypan blue. These isolated cells responded to a variety of secretagogues, the responses being sensitive to the removal of extracellular calcium, increasing extracellular magnesium, and by trifluoperazine, an antagonist of Ca-dependent processes. When exposed to intense electric fields, isolated acinar cells became permeable to CaEGTA and MgATP, these markers gaining access to over 60% of the intracellular milieu within minutes. The accessibility to these markers seemed independent of the ionised Ca2+ level. Less than 0.5% of the cellular amylase was released when cells were rendered leaky in a medium containing about 10(-9) M Ca2+, but typically 4% was released when the Ca2+ level was subsequently raised to 10(-5)M levels, the EC50 for Ca2+ being 2 microM. This amount of amylase released was comparable to the amounts secreted from intact cells in response to a variety of agonists. The cytosolic marker lactate dehydrogenase was also released from leaky cells, but the extent was independent of Ca2+ concentration. No amylase was released at 10(-7)M Ca2+ when permeable cells were exposed to cyclic 3',5'-AMP or cyclic 3',5'-GMP. The calcium activation curve for amylase release seemed to be independent of cyclic nucleotides, but was markedly increased in both the extent of release and apparent affinity for Ca2+ in the presence of the phorbol ester 12-0-tetradecanoyl phorbol 13 acetate. These results suggest that when "functionally normal" isolated acinar cells are rendered permeable, Ca2+-but not cyclic nucleotides-acts as a second messenger for amylase secretion, and furthermore that protein kinase C may be involved in the secretory process.


Management of paranasal sinus neoplasms invading the orbit.
Sinus tumors can readily invade the orbit through their shared walls. The initial symptoms of a sinus neoplasm are often due to orbital invasion. A comprehensive overview of the pathology, diagnosis, and treatment of these tumors is presented.


Autophagy/virophagy: a "disposal strategy" to combat COVID-19.
Given the devastating consequences of the current COVID-19 pandemic and its impact on all of us, the question arises as to whether manipulating the cellular degradation (recycling, waste disposal) mechanism known as macroautophagy/autophagy (in particular, the selective degradation of virus particles, termed virophagy) might be a beneficial approach to fight the novel coronavirus, SARS-CoV-2. Knowing that "autophagy can reprocess everything", it seems almost inevitable that, sooner rather than later, a further hypothesis-driven work will detail the role of virophagy as a fundamental "disposal strategy" against COVID-19, yielding most needed therapeutic interventions. Abbreviations: ATG, autophagy-related; CoV/CoVs coronavirus/coronaviruses; COVID-19, coronavirus disease 2019; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.


A revision of the freshwater crab genus Hainanpotamon (Crustacea: Decapoda: Brachyura: Potamidae: Potamiscinae), with a redescription of Potamon (Potamon) orientale (Parisi, 1916) and descriptions of three new species.
The taxonomy of the potamid genus Hainanpotamon , from Vietnam, Laos, Hainan Island (China) and, purportedly, Okinawa Island (Japan) is reviewed. The type species, Potamon (Potamon) orientale (), is redescribed and a lectotype designated. In addition, three new species are described. The poorly known species Potamon (Geothelphusa) globosum , is assigned to Hainanpotamon and its taxonomy clarified, with a lectotype designated. A key to the nine species of Hainanpotamon is provided.


The Yersinia enterocolitica situation in Denmark.
The importance of pigs as the major Y. e. 0:3 reservoir is strengthened by the Danish investigations. Y.e. 0:3 is the only cause of yersiniosis in Denmark, and approximately 800 cases are recorded yearly. Approximately 10% of the Danish population harbour the HLAB27 factor, thus belonging to the high-potential risk group. In order to minimize the population's risk, important preventive measures by changing the slaughtering technique have now been taken.


Positive arthrography of the craniocervical joints.
The configuration of the articular cavities of the cervico-occipital region have been demonstrated by an experimental technic of positive contrast arthrography in postmortem specimens.


Direct and indirect effects of predatory wasps (Polistes sp.: Vespidae) on gregarious caterpillars (Hemileuca lucina: Saturniidae).
We examined how predation by vespid wasps,Polistes dominulus andP. fuscatus, affected the behavior, growth rate and survivorship of aggregated caterpillars ofHemileuca lucina (Saturniidae). Although these larvae can exhibit a variety of defense and escape behaviors, in general larvae reacted to wasp attacks by clinging to the hostplant. Neighboring larvae in the aggregation responded by leaving the feeding site and moving to the interior or base of the plant. To determine wheter wasp attack affected the behavior and growth of the caterpillars that escaped, a field experiment was conducted with treatments of: 1) larvae exposed to wasps, 2) larvae protected from wasps, and 3) larvae protected from wasps but with the attack of wasps simulated (=harassment). Over just one instar, protected larvae gained significantly more weight than the harassed larvae, which in turn weighed significantly more than the larvae that escaped the wasps. The behavior of attacked and harassed larvae differed from that of the protected larvae; the disturbed larvae often fed in smaller groups and in shaded portions of the plant where only mature leaves were available. A laboratory experiment showed that at 35° C (daytime temperature) larvae had significantly higher relative growth rates and significantly shorter instar duration than larvae reared at 25° C. Our results suggest that wasps, in addition to killing caterpillars, indirectly affect larval fitness by slowing larval growth, at least in part by forcing larvae into cooler microhabitats where leaves are of lower quality.


Transcription factor 4 and myocyte enhancer factor 2C mutations are not common causes of Rett syndrome.
The systematic screening of Rett syndrome (RTT) patients for pathogenetic sequence variations has focused on three genes that have been associated with RTT or related clinical phenotypes, namely MECP2, CDKL5, and FOXG1. More recently, it has been suggested that phenotypes associated with TCF4 and MEF2C mutations may represent a form of RTT. Here we report on the screening of the TCF4 and MEF2C genes in a cohort of 81 classical, atypical, and incomplete atypical RTT patients harboring no known mutations in MECP2, CDKL5, and FOXG1 genes. No pathogenetic sequence variations were identified in the MEF2C gene in our cohort. However, a frameshift mutation in TCF4 was identified in a patient with a clinical diagnosis of "variant" RTT, in whom the clinical evolution later raised the possibility of Pitt-Hopkins syndrome. Although our results suggest that these genes are not commonly associated with RTT, we note the clinical similarity between RTT and Pitt-Hopkins syndrome, and suggest that RTT patients with no mutation identified in MECP2 be considered for molecular screening of the TCF4 gene.


Global dynamics of an SEIR epidemic model with saturating contact rate.
Heesterbeek and Metz [J. Math. Biol. 31 (1993) 529] derived an expression for the saturating contact rate of individual contacts in an epidemiological model. In this paper, the SEIR model with this saturating contact rate is studied. The basic reproduction number R0 is proved to be a sharp threshold which completely determines the global dynamics and the outcome of the disease. If R0 < or =1, the disease-free equilibrium is globally stable and the disease always dies out. If R0 > 1, there exists a unique endemic equilibrium which is globally stable and the disease persists at an endemic equilibrium state if it initially exists. The contribution of the saturating contact rate to the basic reproduction number and the level of the endemic equilibrium is also analyzed.


Pulmonary spindle cell carcinoma presenting with hemothorax.
Spontaneous hemothorax is less common. We report the case of an 83-year-old woman with spontaneous hemothorax caused by lung cancer with nontuberculous mycobacteriosis. She presented with chest pain and hemoptysis. Computed tomography revealed a tumor in the right middle lobe with middle syndrome and pleural effusion. Hemothorax was confirmed, and the right middle lobe was resected to control bleeding. The lung tumor invaded the mediastinal tissue, and tumor rupture was observed. Histological examination revealed pulmonary spindle cell carcinoma and epithelioid granulomas with caseous necrosis. Rapid tumor growth and mediastinal invasion could have led to intratumoral hemorrhage and tumor rupture.


Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic flavonoids. Metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo.
Quercetin is highly mutagenic in vitro, yet is not carcinogenic when administered chronically at large doses to rodents for 12 months. We hypothesized that catechol-O-methyltransferase-catalyzed O-methylation of quercetin and other mutagenic catechol-containing flavonoids may provide an efficient inactivation in vivo and may therefore prevent tumor induction by these flavonoids. After one intraperitoneal administration of 50 mg/kg quercetin to hamsters, a urinary ether extract contained 2% quercetin and 97% 3'-O-methylquercetin. When the urine was treated first with beta-glucuronidase and sulfatase, 13% quercetin and 87% 3'-O-methylquercetin were recovered. Quercetin was rapidly O-methylated by either porcine liver or hamster kidney catechol-O-methyltransferase, with Km values of 6.1 and 6.9 microM and Vmax values of 14,870 and 200 pmol/mg of protein/min, respectively. S-Adenosyl-L-homocysteine exhibited a potent feedback inhibition of the catechol-O-methyltransferase-catalyzed O-methylation of quercetin by a competitive mechanism with respect to S-adenosyl-L-methionine and by a competitive plus noncompetitive mechanism with respect to the substrate. A comparison of the O-methylation rates and kinetic characteristics (Km, Vmax, and Vmax/Km) demonstrated that rates of O-methylation of quercetin and fisetin were up to three orders of magnitude higher than those of catechol estrogens and catecholamines. In conclusion, the rapid metabolic inactivation of mutagenic flavonoids catalyzed by catechol-O-methyltransferase may be a major reason for the lack of their carcinogenic activities in vivo.


Effects of subthalamic nucleus stimulation on the micturation reflex in cats.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) has been performed to reverse motor dysfunction in severe parkinsonian patients. Recent studies suggested that neural circuitry in the basal ganglia might regulate micturition function as well. In 15 adult male cats under ketamine anesthesia, in which spontaneous isovolumetric micturition reflex had been generated, we performed electrical stimulation and extracellular single unit recording in the STN. Electrical stimulation applied in the STN elicited inhibition of the micturition reflex. None of the responses was facilitatory. Effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 microA, which gradually increased and exceeded 250 microA as the location of the stimulation exceeded an area of the STN. Effective frequency of the electrical stimulation with given stimulus intensity was 50 Hz and higher. Total 10 neurons were recorded in the STN that were related to urinary storage/micturition cycles. All neurons were tonically active throughout storage/micturition cycles with storage phase predominance, with almost constant firing activities during the storage phase. In conclusion, our results showed that HFS-STN inhibited the micturition reflex and there were micturition-related neuronal firings in the STN in cats, suggesting the STN may be involved in neural control of micturition. The results also provide an implication that clinical HFS-STN may alter urinary function in parkinsonian patients.


Incorporation of a virtual assessment into a care pathway for initial glaucoma management: feasibility study.
To investigate the feasibility of a glaucoma triage assessment based on the consideration of clinical data in a virtual clinic environment. One hundred consecutive new patients were assessed by masked observers for a possible diagnosis of glaucoma or ocular hypertension by evaluation of clinical data compiled by a technician in the absence of the patient. The virtual clinic diagnoses were compared with those made by actual examination of the patient in the outpatient clinic. A total of 22% of subjects were excluded from interobserver comparison because of atypical scanning laser ophthalmoscopy. Of the 78% of subjects completing virtual and actual clinical assessments diagnostic agreement was good, weighted Kappa was of 0.72 (95% confidence interval 0.85 to 0.59), sensitivity 94.4% and specificity 86.7%. No case of glaucoma was misdiagnosed as normal by virtual assessment. Clinical findings and data relating to glaucoma may be evaluated in a virtual clinic with satisfactory diagnostic accuracy.


Kinase hinge binding scaffolds and their hydrogen bond patterns.
Protein kinases constitute a major class of intracellular signaling molecules, and describe some of the most prominent drug targets. Kinase inhibitors commonly employ small chemical scaffolds that form hydrogen bonds with the kinase hinge residues connecting the N- and C-terminal lobes of the catalytic domain. In general the satisfied hydrogen bonds are required for potent inhibition, therefore constituting a conserved feature in the majority of inhibitor-kinase interactions. From systematically analyzing the kinase scaffolds extracted from Pfizer crystal structure database (CSDb) we recognize that large number of kinase inhibitors of diverse chemical structures are derived from a relatively small number of common scaffolds. Depending on specific substitution patterns, scaffolds may demonstrate versatile binding capacities to interact with kinase hinge. Afforded by thousands of ligand-protein binary complexes, the hinge hydrogen bond patterns were analyzed with a focus on their three-dimensional configurations. Most of the compounds engage H6 NH for hinge recognition. Dual hydrogen bonds are commonly observed with additional recruitment of H4 CO upstream and/or H6 CO downstream. Triple hydrogen bonds accounts for small number of binary complexes. An unusual hydrogen bond with a non-canonical H5 conformation is observed, requiring a peptide bond flip by a glycine residue at the H6 position. Additional hydrogen bonds to kinase hinge do not necessarily correlate with an increase in potency; conversely they appear to compromise kinase selectivity. Such learnings could enhance the prospect of successful therapy design.


New generation dopaminergic agents. 2. Discovery of 3-OH-phenoxyethylamine and 3-OH-N1-phenylpiperazine dopaminergic templates.
Described in this report is a systematic study which led to the identification of two new dopamine D2 partial agonists (5 and 17). Phenols 5 and 17 represent prototypes of two new classes of D2 partial agonists as well as templates for the future design of novel dopaminergic agents.


Radioreceptor assay for insulin formulations.
A sensitive radioreceptor assay was developed for pharmaceutical insulin formulations with the use of rat liver membranes and 125I-insulin. The addition of unlabeled insulin or insulin analogues inhibited the binding of 125I-insulin to the receptors in a concentration-dependent way. Insulin concentrations between 3 x 10(-9) and 3 x 10(-8) M were used for a three-point assay which fulfilled pharmacopoeial statistical requirements for validity of the assay. The coefficient of variation for five assays was 4%. Potency estimates of insulin preparations obtained with the radioreceptor assay correlated well with corresponding estimates from in vivo assays. Both assays also gave similar potency readings for insulin preparations that were partly degraded during storage at elevated temperatures, but the radioreceptor method was more precise.


Season, sex and age as modifiers in the association of psychosis morbidity with air pollutants: A rising problem in a Chinese metropolis.
Until now, epidemiological studies on the association between psychosis morbidity and air pollutants are scarce, especially in a developing country. Thus, a time-series analysis on the short-term association between the daily disease (psychosis and non-accidental) morbidity and air pollutants including particulate matter (PM) with diameters of 10 μm or less (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was firstly conducted. The association between daily psychosis morbidity stratified by sex and age, and outdoor air pollutants in Tianjin as an important metropolis in China was examined. The psychosis effect from air pollutants in the warm season (April-September) and the cool season (October-March) was also analyzed, respectively. An increase of 10 μg/m(3) in a 2-day average concentration of PM10, SO2, and NO2 corresponded to an increase in all non-accidental morbidity of 0.15%, 0.49%, and 0.57%, respectively. The association between non-accidental morbidity and SO2 in the cool season was significantly different from that in the warm season. These findings might have implications and references for local governments to make policies for air pollution control and management, and public health prevention.


Regional microstructural differences in ADHD youth with and without a family history of bipolar I disorder.
Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC). A total of 140 (high-risk, n = 44; low-risk, n = 49; and HC, n = 47) youth (mean age: 14.1 ± 2.5 years, 65 % male) were included in the analysis. Diffusion tensor images were collected and fractional anisotropy (FA) and mean diffusivity (MD) maps were calculated. Both tract-based and voxel-based analyses were performed. Correlations between clinical ratings and microstructural metrics that differed among groups were examined. No significant group differences in major long-distance fiber tracts were observed. The high-risk ADHD group exhibited predominantly higher FA and lower MD in frontal, limbic, and striatal subregions compared with the low-risk ADHD group. Both low-risk and high-risk ADHD groups exhibited higher FA in unique and overlapping regions compared with HC subjects. Significant correlations between regional microstructural metrics and clinical ratings were observed in ADHD groups. Prospective longitudinal studies will be required to determine the relevance of these findings to BD risk progression. Psychostimulant-free ADHD youth with a BD family history exhibit different microstructure alterations in frontal, limbic, and striatal regions compared with ADHD youth without a BD family history, and may therefore represent a unique phenotype relevant to BD risk progression.


Effect of salinity on removal performance of anaerobic membrane bioreactor treating azo dye wastewater.
Membrane bioreactor (MBR) is an attractive option method for treating azo dye wastewater under extreme conditions. The present study assessed the effect of salinity on the performance of anaerobic MBR in treating azo dye wastewater. Increased salinity showed adverse effects on the decolorization efficiency and chemical oxygen demand (COD) removal efficiency. The decolorization efficiency decreased from 95.8% to 82.3% and 73.1% with a stepwise increasing of salinity from 0 to 3% and 5%, respectively. The COD removal efficiency decreased from 80.7% to 71.3% when the salinity increased from 0 to 3% and then decreased to 58.6% at 5% salinity. The volatile fatty acids (VFAs) concentration also increased as the salinity increased. Furthermore, increased salinity led to the elevated production of soluble microbial products (SMP) and extracellular polymeric substances (EPS), which can provide a protective barrier against harsh environments. More serious membrane fouling was observed as the SMP and EPS concentrations increased. The concentration of loosely bound EPS (LB-EPS), tightly bound EPS (TB-EPS), and the polysaccharide/protein (PS/PN) ratios in LB-EPS and TB-EPS all increased when the salinity was elevated. The production of SMP and EPS was caused by the generation of PS in response to the saline environment. Lactobacillus, Lactococcus, Anaerosporobacter, and Pectinatus were the dominant bacteria, and Lactobacillus and Lactococcus were the decolorization bacteria in the MBR. The lack of halophilic bacteria was the main reason for the decreased decolorization efficiency in the salinity environment.


Expression pattern of the urokinase-plasminogen activator system in rat DS-sarcoma: role of oxygenation status and tumour size.
The urokinase plasminogen activator system plays a central role in malignant tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen activator, urokinase plasminogen activator-receptor and plasminogen activator inhibitor type 1 have been identified as adverse prognostic factors. Upregulation of urokinase plasminogen activator or plasminogen activator inhibitor type 1 could present means by which hypoxia influences malignant progression. Therefore, the impact of hypoxia on the expression pattern of the urokinase plasminogen activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in vivo setting, tumour cells were implanted subcutaneously into rats, which were housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies, DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen activator and urokinase plasminogen activator-receptor expression were analysed by flow cytometry. Urokinase plasminogen activator activity was measured using zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT-PCR. DS-sarcoma cells express urokinase plasminogen activator, urokinase plasminogen activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas compared to normal tissues and rises with increasing tumour volume. The oxygenation level has no impact on the urokinase plasminogen activator activity in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase in plasminogen activator inhibitor type 1 protein and mRNA expression after hypoxic challenge is detectable. The latter plasminogen activator inhibitor type 1 changes were not detectable in vivo. Hypoxia has been demonstrated to contribute to the upregulation of some components of the system in vitro, although this effect was not reproducible in vivo. This may indicate that the serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate marker of tumour hypoxia.


Pseudocapacitive-battery-like behavior of cobalt manganese nickel sulfide (CoMnNiS) nanosheets grown on Ni-foam by electrodeposition for realizing high capacity.
Hierarchical interconnected nanosheets (HIN) of cobalt manganese nickel sulfide (CoMnNiS) were synthesized on Ni foam by a simple and economical electrodeposition technique for energy storage application. Sulfonated thin nanosheets of Co, Mn and Ni provide stability of chemical activity, surface functionalization and surface reactivity to the electrode. The fabricated electrode shows a specific capacity of 257.4 mA h g-1 (at 2.5 A g-1), measured by galvanostatic charging-discharging (GCD). Both diffusion and capacitive mechanisms in the sulfide layer contribute to the high electrical conductivity. Asymmetric devices CoMnNiS/NiCuO and CoMnNiS/CNT (CNT = carbon nanotubes) were fabricated, providing a maximum operating voltage of 1.7 V and 1 V, specific capacity of 20.8 and 50.8 mA h g-1, and energy density of 8.4 and 6.3 W h kg-1 corresponding to a power density of 985 and 211 W kg-1, respectively, at a current density of 0.5 and 0.63 A g-1. These results demonstrate a novel material for application in energy storage devices as an electrode.


Splenic mucinous cystadenocarcinoma arising in heterotopic pancreatic tissue.
A mucinous cystadenocarcinoma along with remnants of normal pancreatic tissue was discovered in the spleen of a 21-year-old woman. Extensive clinical, radiological, ultrasound and computed tomography investigation revealed that the patient's pancreas and ovaries were unremarkable. We presume an origin from heterotopic pancreatic tissue for this neoplasm and present a review of the literature in this regard.


Effect of Rebaudioside A, a diterpenoid on glucose homeostasis in STZ-induced diabetic rats.
Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P<0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P<0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P<0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P<0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P<0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes.


Three plasma metabolite signatures for diagnosing high altitude pulmonary edema.
High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.


Mastering morphology of non-fullerene acceptors towards long-term stable organic solar cells.
Despite the rapid progress of organic solar cells based on non-fullerene acceptors, simultaneously achieving high power conversion efficiency and long-term stability for commercialization requires sustainable research effort. Here, we demonstrate stable devices by integrating a wide bandgap electron-donating polymer (namely PTzBI-dF) and two acceptors (namely L8BO and Y6) that feature similar structures yet different thermal and morphological properties. The organic solar cell based on PTzBI-dF:L8BO:Y6 could achieve a promising efficiency of 18.26% in the conventional device structure. In the inverted structure, excellent long-term thermal stability over 1400 h under 85 °C continuous heating is obtained. The improved performance can be ascribed to suppressed charge recombination along with appropriate charge transport. We find that the morphological features in terms of crystalline coherence length of fresh and aged films can be gradually regulated by the weight ratio of L8BO:Y6. Additionally, the occurrence of melting point decrease and reduced enthalpy in PTzBI-dF:L8BO:Y6 films could prohibit the amorphous phase to cluster, and consequently overcome the energetic traps accumulation aroused by thermal stress, which is a critical issue in high efficiency non-fullerene acceptors-based devices. This work provides insight into understanding non-fullerene acceptors-based organic solar cells for improved efficiency and stability.


Evaluation of vitamin D levels in allergic fungal sinusitis, chronic rhinosinusitis, and chronic rhinosinusitis with polyposis.
Vitamin D3 (VD3 ) levels have been recently found to be responsible for a number of immunological, anti-inflammatory and anti-infectious roles. Some studies reported that some forms of allergic fungal rhinosinusitis (AFRS), occurs more commonly in patients who are more susceptible to VD3 deficiency. The aim of this work was to measure VD3 levels in patients with AFRS and chronic rhinosinusitis (CRS). We report a prospective case control study conducted at Ain Shams University. It included 74 participants divided into 4 groups: group A, 25 patients with AFRS; group B, 15 patients with CRS with nasal polyps (CRSwNP); group C: 15 patients with CRS without nasal polyps (CRSsNP); and group D, 19 controls. There was a statistically significant (p < 0.001) difference of VD3 between groups A and B compared with groups C and D. There were no statistically significant differences between the 4 groups regard calcium levels. Finally, there was a statistically significant difference in phosphate levels when we compared groups A and B with groups C and D (p = 0.001). Serum level of VD3 in patient with CRSwNP and AFRS is significantly lower than that of patients with CRSsNP and control subjects. Although these results do not imply a specific etiological or therapeutic relationship, VD3 levels may constitute an inexpensive prophylactic and cost-effective option in the therapeutic armamentarium in the control of AFRS and CRSwNP, either by itself or as a synergistic agent with traditional agents.


Distal pancreatectomy with celiac axis resection for carcinoma of the body and tail of the pancreas.
We retrospectively investigated our experiences with distal pancreatectomy with celiac axis resection (DP-CAR) for locally advanced pancreatic cancer and compared the operative outcome and long-term survival between DP-CAR and standard distal pancreatectomy (DP). Although several authors reported that DP-CAR increases resectability rates, the long-term results of this operation are not clear, and there are few reports presenting a comparison of the short- and long-term results between DP-CAR and DP. From 1993 to 2010, 43 patients with invasive ductal carcinoma of the body or tail of the pancreas underwent a macroscopically curative resection (R0/1). Sixteen patients underwent DP-CAR and 27 patients underwent DP. No DP-CAR patients underwent any preoperative coil embolization of the common hepatic artery (CHA) to stimulate the development of collateral pathways from the superior mesenteric artery. The perioperative and histopathologic parameters and survival data were analyzed to compare the two operations. There was no difference in mean operative time, mean blood loss, postoperative mortality, and morbidity between DP-CAR and DP. The rates of morbidity and in-hospital mortality of DP-CAR were 56 and 6%, respectively. In DP-CAR, 15 patients did not require reconstruction of the hepatic artery and no hepatic infarctions were clinically encountered after surgery. The estimated overall 1- and 3-year survival rates in patients who underwent DP-CAR were 42.6 and 25.6%, respectively, and their survival time was significantly less than that of patients who underwent DP (median survival time: 9.7 vs. 30.9 months, P = 0.033). The R1 resection rates of these groups were 44% in DP-CAR and 22% in DP, respectively. DP-CAR is a safe and rational procedure for locally advanced pancreatic cancer without preoperative embolization of the CHA. Although the short-term results were equivalent to that for DP, DP-CAR did not improve the long-term survival because of the high rate of R1 resection at present.


Hysterectomy surgery trends: a more accurate depiction of the last decade?
The objective of the study was to describe trends in hysterectomy route at a large tertiary center. We reviewed all hysterectomies performed at Magee-Womens Hospital from 2000 to 2010. This database was chosen over larger national surveys because it has been tracking laparoscopic procedures since 2000, well before laparoscopic hysterectomy International Classification of Diseases, ninth revision (ICD-9) procedure codes were developed. There were 13,973 patients included who underwent hysterectomy at Magee-Womens Hospital. In 2000, 3.3% were laparoscopic (LH), 74.5% abdominal (AH), and 22.2% vaginal hysterectomy (VH). By 2010, LH represented 43.5%, AH 36.3%, VH 17.2%, and 3.0% laparoscopic converted to open (LH→AH). Hysterectomies performed for gynecological malignancy represented 24.4% of cases. The average length of stay for benign LH and VH, 1.0 ± 1.0 and 1.6 ± 1.0 days respectively, was significantly shorter than the average 3.1 ± 2.3 day stay associated with AH (P < .001). The average patient age was 46.9 ± 10.9 years for LH, 51.5 ± 12.1 years for AH, and 51.7 ± 14.1 years for VH, and over the study period there was a significant trend of increasing patient age (b1 = 0.517, 0.583, and 0.513, respectively [P < .001 for all]). The percentage of LH increased over the last decade and by 2010 had surpassed AH. The 43.4% LH rate in 2010 is much higher than previously reported in national surveys. This likely is due to an increase in the number of laparoscopic procedures being performed over the last few years as well as the ability of our study to capture LH prior to development of appropriate ICD-9 procedure codes. Our unique ability to determine hysterectomy route, which predates appropriate coding, may provide a more accurate characterization of hysterectomy trends.


Immunocompromised Child on Infliximab: A Case Report of Listeria monocytogenes Meningitis.
Patients with naturally occurring, impaired cell-mediated immunity secondary to age and pregnancy are known to be at risk of developing severe and invasive Listeria monocytogenes infections. Immunosuppressant medications, particularly infliximab, are also known to increase this risk. We present the case of a seven-year-old female on infliximab who was diagnosed with culture positive L. monocytogenes meningitis after a negative cerebral spinal fluid polymerase chain reaction (PCR). Patients receiving infliximab who display signs of central nervous system infection should be suspected to have L. monocytogenes as an infecting agent, and empiric addition of ampicillin to their antibiotic regimen should be considered, with substitution of trimethoprim-sulfamethoxazole in cases of penicillin allergy, regardless of initial PCR results.


Human skin allografts as a useful adjunct in the treatment of purpura fulminans.
The aim of this report is to discuss the role of human skin allografts in surgical coverage procedures for patients with purpura fulminans. We describe cases of purpura fulminans in three adults and one infant treated at our burns unit between October 2006 and January 2008. The application of cryopreserved human skin allografts allowed us to obtain immediate wound closure after necrosis excision and enabled our team to subsequently perform autografts on favourable graft recipient sites. Recourse to human skin allografts must be considered a pertinent therapeutic option in patients with purpura fulminans.


Primary malignant hemangioendothelioma of the liver: survival following nonoperative treatment.
A case of primary hemangioendothelioma is presented. Following autodearterialization, the patient received 5-fluorouracil orally and total hepatic radiation. To date, 30 months later, he remains alive and active with residual hepatic defect on liver scan, but no indication of progression of disease. Primary malignant hemangioendothelioma is discussed briefly in terms of etiology, pathology, diagnosis, and treatment, and a treatment plan is presented. This case also presented an unusual side effect of 5-fluorouracil therapy -- mononeuritis multiplex -- and is presented out of interest.


The interplay of context factors in hypnotic and sedative prescription in primary and secondary care-a qualitative study.
Non-medical or contextual factors strongly influence physicians' prescribing behavior and may explain why drugs, such as benzodiazepines and Z-drugs, are still frequently prescribed in spite of well-known adverse effects. This study aimed to explore which contextual factors influence the prescription of hypnotics and sedatives and to compare their role in primary and secondary care. Understanding medical practices as games with specific rules and strategies and performed in a largely habitual, not fully conscious manner, we asked a maximum variation sample of 12 hospital doctors and 12 general practitioners (GPs) about their use of hypnotics and sedatives. The interviews were analyzed by qualitative content analysis. Hospital doctors' and GPs' use of hypnotics and sedatives was influenced by a variety of contextual factors, such as the demand of different patient groups, aims of management, time resources, or the role of nurses and peers. Negotiating patient demands, complying with administrative regulations, and finding acceptable solutions for patients were the main challenges, which characterized the game of drug use in primary care. Maintaining the workflow in the hospital and finding a way to satisfy both nurses and patients were the main challenges in secondary care. Even if doctors try to act rationally, they cannot escape the interplay of contextual factors such as handling patient needs, complying with administrative regulations, and managing time resources. Doctors should balance these factors as if they were challenges in a complex game and reflect upon their own practices.


Effects of storage temperature, storage duration, and subsequent ripening on the physicochemical characteristics, volatile compounds, and phytochemicals of Western Red nectarine (Prunus persica L. Batsch).
Western Red nectarines, harvested at commercial maturity, were stored for up to 20 days at 1, 4, or 8 °C and then transferred to 25 °C for 0 or 4 days. The main physicochemical attributes, phytochemicals, and volatile compounds were then determined. During storage and ripening, firmness, titratable acidity, organic acids, and C6 volatile compounds decreased, whereas ethylene production, lactones, and C13 norisoprenoids greatly increased. Soluble solids content, sugars, and polyphenols remained quite constant during both stages. During storage, vitamin C decreased and carotenoids did not significantly change, whereas both greatly increased during ripening. Increased time of low-temperature storage has been found to decrease lactones and C13 norisoprenoids in nectarine and, consequently, to limit its aroma during maturation. Finally, Western Red nectarine was found hardly chilling injury sensitive, and trends for sugars, polyphenols and lactones observed in this study were contrary to those generally reported in the literature for chilling-injured fruit.


Evaluating the impacts of small cascade hydropower from a perspective of stream health that integrates eco-environmental and hydrological values.
With small cascade hydropower projects (SCHPs) increasingly employed in small and medium rivers, methods to assess changes in health status within the stream system have become essential to river ecological environment management. In this study, we used a cloud based fuzzy evaluation method to synthetically diagnose the health status of a stream, both as a whole and its parts (hydrological regime, riparian landscape, aquatic community, water quality, and social demand), under the impacts of SCHPs. The results indicated that: (1) average maximum and minimum flows decreased by 20% and 10% respectively, since SCHPs were implemented. Furthermore, the 38% increase in low flow frequency indicated that SCHPs might amplify droughts, the opposite of large hydropower projects which have been shown to alleviate drought; (2) implementation of SCHPs enhanced heterogeneity and fragmentation in riparian landscapes and decreased diversity of riparian vegetation, and dominant species were more likely to emerge on the upstream side of dam; (3) diversity of phytoplankton, zooplankton, and benthic animals decreased by 14%, 4%, and 16%, respectively, during high-impact period (HIP); and fish species decreased by 26% with a shift from rapid flow adapted to lentic and slow flow adapted species; and (4) the stream still exhibited a healthy state during HIP, but the degree of certainty belonging to "healthy" decreased from 0.279 to 0.192, indicating that the stream health was nearing a deteriorated state. This evaluation model clarified imperceptible and fuzzy changes in stream health which will be helpful in follow-up management decisions.


Generation and maintenance of Dmbx1 gene-targeted mutant alleles.
Dmbx1 encodes a paired-like homeodomain protein that is expressed in neural tissues at mouse embryonic and postnatal stages. We previously generated two Dmbx1 mutant alleles, Dmbx1 (-) and Dmbx1 ( z ), by homologous recombination in mouse embryonic stem (ES) cells. In this article we report the generation of three novel Dmbx1 mutant alleles, Dmbx1 (tauZ ), Dmbx1 (tauG ), and Dmbx1 ( Cre ), that carry the intronic insertion of tau (tau)-lacZ, tau-eGFP, and Cre reporter genes, respectively. Dmbx1 (tauZ ) and Dmbx1 (tauG ) recapitulated the Dmbx1 expression, and the reporter gene expression was detected in the diencephalon and mesencephalon during embryogenesis. The crossing of Dmbx1 ( Cre ) mice with Rosa26 reporter mice identified the Cre-mediated DNA excision in the postnatal midbrain, cerebellum, medulla oblongata, and spinal cord. To maintain the Dmbx1 mutant alleles without genotyping, we crossed Dmbx1 mutant mice with Inv4(1) ( Brd ) mice that possess the inversion between D4Mit117 and D4Mit281 on Chromosome 4, where Dmbx1 is located. The intercrossing of the non-agouti (a/a) albino (Tyr ( c-Brd )/Tyr ( c-Brd )) Dmbx1 mutant mice carrying Inv4(1) ( Brd ) tagged with K14-Agouti and Tyrosinase coat-color markers resulted in the generation of dark brown Dmbx1 wild-type [Inv4(1) ( Brd )/Inv4(1) ( Brd )], light brown Dmbx1 heterozygous [Dmbx1 ( tm )/Inv4(1) ( Brd )], and albino Dmbx1 homozygous (Dmbx1 ( tm )/Dmbx1 ( tm )) mutant mice. To our knowledge, this is the first demonstration of the proof-of-principle of the maintenance of viable gene-targeted alleles using coat-color-tagged nonlethal balancer chromosomes.


Rapid and sensitive smartphone non-enzymatic colorimetric assay for the detection of glucose in food based on peroxidase-like activity of Fe3O4@Au nanoparticles.
A low-cost and reliable analytical method based on the combination of a newly designed Fe3O4@Au as peroxidase mimetics, supported on smartphone analysis software package was proposed for the determination of glucose content in food samples. The nanocomposite was prepared by self-assembling technique, and the characterization was carried out using transmission electron microscopy (TEM), Fourier transforms infrared, and X-ray diffractometer. Record the color change of the solution with a smartphone camera and optimize the operation parameters and reaction conditions. A smartphone with a free self-developed app was accustomed live the RGB (red-greenblue) values of color intensity within the Fe3O4@Au system and were processed with Image J software before computationally convert them glucose concentrations. At the optimization experiment, reaction temperature of 60 °C, reaction time of 50 min and the amount of addition of Fe3O4@Au 0.0125 g was the optimal combination of detecting glucose smartphone color detection system. Hereon, the accuracy of the proposed method was evaluated by comparison between smartphone colorimetry and UV-vis spectrophotometer, a linear calibration in the range of 0.25 ∼ 15 mmol/L glucose was obtained with minimum detection limit of 1.83 and 2.25 μmol/L, respectively. The proposed method was applied effectively to the detection of glucose in actual samples. The results were in accordance with the conventional UV-vis spectrophotometer method.


Effectiveness of adjunctive nebulized antibiotics in critically ill patients with respiratory tract infections.
The purpose of the study was to analyze the effectiveness of adding nebulized antibiotics to systemic antimicrobials in critically ill patients with respiratory tract infections (pneumonia or tracheobronchitis) and the effect on renal function. A retrospective observational cohort study including critically ill patients with respiratory tract infections during a 2-year period was conducted. Intervention group included patients that received nebulized and systemic antimicrobials. Patients in the control group received only systemic antimicrobials. Clinical resolution was the primary endpoint. Secondary outcomes included change in fever, inflammatory parameters, and creatinine clearance; length of hospital stay, systemic therapy, and mechanical ventilation; hospital readmission; and mortality. Regression models were performed to estimate the effect of nebulized antibiotics on outcome variables adjusted by potential confounders. A total of 136 patients were included (93 in control group and 43 in intervention group). The intervention group had higher odds of clinical resolution (adjusted odds ratio (OR): 7.1; 95% confidence interval (95% CI): 1.2, 43.3). Nebulized antibiotic therapy was independently associated with reduction in procalcitonin (adjusted OR: 12.4; 95% CI: 1.4, 109.7). There were no significant differences in the rest of the secondary outcomes or in creatinine clearance reduction. Adding nebulized antibiotics for the management of respiratory tract infections has a positive impact on clinical resolution without increasing the risk of renal toxicity.