Attracting Future Radiation Oncologists: An Analysis of the National Resident Matching Program Data Trends From 2004 to 2015.
A significant physician shortage has been projected to occur by 2025, and demand for oncologists is expected to outpace supply to an even greater degree. In response to this, many have called to increase the number of radiation oncology residency positions. The purpose of this study is to evaluate National Resident Matching Program (NRMP) data for the number of residency positions between 2004 and 2015 as well as the number and caliber of applicants for those positions and to compare radiation oncology to all residency specialties. NRMP data for all specialties participating in the match, including radiation oncology, were assessed over time examining the number of programs participating in the match, the number of positions offered, and the ratio of applicants to positions in the match from 2004 to 2015. From 2004 to 2015, the number of total programs participating in the match has increased by 26.7%, compared to the increase of 28.6% in the number of radiation oncology programs from during the same time period. The total number of positions offered in the match increased by 53.4%, whereas radiation oncology positions increased by 56.3%, during the same time period. The ratio of applicants (defined as those selecting a specialty as their first or only choice) to positions for all specialties has fluctuated over this time period and has gone from 1.21 to 1.15, whereas radiation oncology experienced a decrease from 1.45 to 1.14. NRMP data suggest that senior medical student applications to radiation oncology are decreasing compared to those of other specialties. If we hope to continue to attract the best and brightest to enter our field, we must continue to support early exposure to radiation oncology, positive educational experiences, and dedicated mentorship to interested medical students.


Comprehensive geriatric care in a day hospital: a demonstration of the British model in the United States.
A geriatric day hospital (GDH) was developed in a community hospital to meet the complex medical and social needs of the frail elderly. A review of medical records (n = 273) and interviews with referring physicians (n = 42 on 96 patients) revealed that the GDH provided intensive outpatient care, geriatric assessment, rehabilitation, and an alternative to hospitalization. In all, 21% of physician-referred patients would have been hospitalized without the GDH, 7% would have had longer hospital stays, and care would have been deferred for 18%.


Factor-VIII activity and antigen, platelet count and biochemical changes after adrenoceptor stimulation.
Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI, and XII, platelet count, lactate, pyruvate, potassium and free fatty acids. Factor VIII was studied by clotting assays, by reactions with two rabbit antisera and two human antibodies, and by desulphated agarose chromatography. At the rate at which they were adiminstered, all three drugs increased the pulse rate by 20-40 beats/min. Factor VIII rose c. 2.5 X with adrenaline but only c. 1.5 X with isoprenaline and salbutamol; but other clotting factors did not alter. Chromatography provided no evidence of a change in the size of the molecule carrying factor-VIII clotting activity. The rate of clearance of the heightened plasma activity could not be shown to differ from that of "ordinary" factor VIII infused into haemophiliacs. The platelet count rose after adrenaline, fell after salbutamol and did not change significantly after isoprenaline. Among the biochemical responses, the only significant difference between the drugs was that lactate rose after adrenaline and salbutamol but did not change after isoprenaline. The rise in factor-VIII clotting activity after adrenaline is considered to represent a real increase in blood concentration, presumably by release of additional factor VIII from stores. The evidence suggests that this could be classified as a beta2 effect; and that the quantity which can be released is unrelated to the current plasma level. The rise in platelet count produced by adrenaline may be the resultant of an alpha-mediated rise due to contraction of the exchangeable splenic pool and a beta2-mediated fall, the alpha effect predominating.


Ethanol-induced alteration in activities of cerebral phosphatidylinositol 4,5-biphosphate-specific and cytosolic phospholipase C in the brain: analysis using NG 108-15 cells and brains from ethanol-inhaled mice.
Effect of long-term exposure to ethanol (EtOH) on the phosphatidylinositol 4,5-biphosphate (PIP2)-specific and cytosolic phospholipase C (PLC) activities in neuroblastoma x glioma hybrid (NG 108-15) cells and the brains from EtOH-inhaled mice were investigated. Long-term (2 days) exposure of NG 108-15 cells to EtOH induced significant decrease in PIP2-specific PLC activity dependent on concentration and duration of exposure, although the presence of EtOH in the enzyme assay system induced no alteration in PIP2-specific PLC activity. On the other hand, cytosolic PLC activity in NG 108-15 cells significantly increased by both the long-term exposure of the cells to EtOH and the addition of EtOH into the assay system. These changes in activities of both types of PLC in NG 108-15 cells observed after EtOH exposure recovered rapidly by the removal of EtOH. Moreover, the changes in activities of PIP2-specific and cytosolic PLC in the brain of EtOH-inhaled mice were similar to those found in NG 108-15 cells. These results indicate that EtOH inhibits the activity of PIP2-specific PLC and activates cytosolic PLC in the brain. These changes in cerebral PLC activities are suggested to involve in central action of EtOH and establishment of alcohol dependence.


Effects of branched chain enriched amino acid solutions on septic rats.
An experimental study was performed to determine the effects of a BCAA enriched amino acid solution on sepsis in rats. After sepsis had been induced in male Wistar rats by caecal ligation and puncture the animals were divided into four groups according to the amino acid solutions infused: Group B-I, a solution containing no amino acid; Group B-II, a commercially available solution containing 21.1% branched chain amino acids (BCAA); Group B-III, a solution containing 38.7% BCAA and Group B-IV, that containing BCAA only. The control group of the animals received simple laparotomy and infusion without amino acids. Infusion was continued for 96 hours after the operation and all the solutions had the same caloric and nitrogen value. Group B-I had a plasma aminogram peculiar to sepsis; a significant rise in the concentration of the total 17 amino acids (TAA), BCAA and aromatic amino acid (AAA) together with a decrease in the BCAA/AAA ratio. Furthermore, the arterio-venous difference (AV-D) of AAA and BCAA showed a large negative value. In the three groups infused with amino acids, only Group B-III showed a significant improvement in the survival rate and nitrogen balance compared with Group B-I. Moreover, not only did the concentration of TAA and AAA significantly decline, but also the BCAA/AAA ratio increased. Therefore, the abnormal aminogram in sepsis tended to return to the control level. In Group B-IV despite the significant decrease of the peripheral TAA, no improvement in plasma aminogram, nitrogen balance or survival rate were shown. In Group B-II, in addition to the persisting plasma aminogram changes and peripheral efflux of amino acids, no improvement of survival rate were noted. Therefore, it was concluded that an amino acid composition richer in BCAA and lower in both AAA and SCAA is beneficial in the treatment of sepsis.


A general route to xyloglucan-peptide conjugates for the activation of cellulose surfaces.
Cellulose is an attractive supporting matrix for diverse biotechnological applications, including chromatography, diagnostics, and tissue replacement/scaffolding, due to its renewable resource status, low cost, and low non-specific interaction with biomolecules. In an effort to expand the biofunctionality of cellulose materials, we present here a versatile method for the synthesis of xyloglucan-peptide conjugates that harness the strong xyloglucan-cellulose binding interaction for gentle surface modification. Xylogluco-oligosaccharide aminoalditols (XGO-NH(2)) were coupled to both linear and cyclic peptides, which contained the endothelial cell epitope Arg-Gly-Asp, in a facile two-step approach employing diethyl squarate cross-linking. Subsequent xyloglucan endo-transglycosylase-mediated coupling of the resulting XGO-GRGDS (Gly-Arg-Gly-Asp-Ser) and XGO-c[RGDfK]-PEG-PEG (cyclo[Arg-Gly-Asp-(D-Phe)-Lys]-PEG-PEG; where PEG is 8-amino-3,6-dioxaoctanoic acid) conjugates into high molecular mass xyloglucan yielded xyloglucan-RGD peptide conjugates suitable for cellulose surface activation. Notably, use of XGO-squaramate as a readily accessible, versatile intermediate overcomes previous limitations of solid-phase synthetic approaches to XGO-peptide conjugates, and furthermore allows the method to be generalized to a wide variety of polypeptides and proteins, as well as diverse primary amino compounds.


Identification of a novel LATS1 variant associated with familial cerebral cavernous malformations in a Chinese family.
Cerebral cavernous malformations (CCMs) are common sporadic or hereditary vascular malformations in the central nervous system. CCM1-3 variants have been identified that are associated with the majority of familial cerebral cavernous malformations (FCCMs). However, there are still a few CCM1-3 wild-type FCCMs. The aim of the present study was to identify an additional pathogenic variant of FCCMs. In this study, a large five-generation Chinese Han family affected by CCMs was recruited. Magnetic resonance imaging (MRI) was done for the detection of CCMs. Whole-exome sequencing (WES) was performed, and the identified variants were co-segregation analyzed by Sanger sequencing. The function of candidate variants was predicted in silico and experimental validated by angiogenesis assay in human umbilical vein endothelial cells (HUVECs) in vitro. Twenty-four family members and one healthy spouse were enrolled. We found that CCMs were exhibited on MRI in nine family members. Overall, twenty-seven candidate variants were identified using WES, and no CCM1-3 variants were detected. The missense variant in LATS1 (c.821C > T, p.Thr274Ile) was verified to be associated with the clinical and pathological phenotype of FCCMs. Our findings indicated that the LATS1 variant could be a potential pathogenic factor for FCCMs in this Chinese family.


Non-enzymatic covalent modifications of proteins: mechanisms, physiological consequences and clinical applications.
Given the complexity of the biosynthetic machinery and the delicate chemical composition of proteins, it is remarkable that cells manage to produce and maintain normally functioning proteins under most conditions. However, it is now well known that proteins are susceptible to various non-enzymatic covalent modifications (NECM) under physiological conditions. Such modifications can be of no or little importance to the protein or they can be absolutely detrimental. Often NECM are difficult to study due to the complex and technically demanding methods required to identify many of these modifications. Thus, the role of NECM has not yet been adequately resolved but recent research has allowed a better understanding of such modifications. The present review outlines the various forms of NECM that involve covalent modifications of proteins, and discusses their relevance, biological impact and potential applications in the study of protein turnover and diagnosis of disease.


Subependymal giant-cell astrocytoma associated with tuberous sclerosis. Do subependymal nodules grow?
A case of a 10 year-old-boy with subependymal giant-cell astrocytoma associated with tuberous sclerosis is reported. Sequential CT scan showed the growth of subependymal nodules to intraventricular neoplasm, which consequently obstructed the CSF pathway. The surgical indications for this lesion and the role of CT in following up subependymal nodules of tuberous sclerosis are discussed.


Malaria Epidemiology at the Clone Level.
Genotyping to distinguish between parasite clones is nowadays a standard in many molecular epidemiological studies of malaria. It has become crucial in drug trials and to follow individual clones in epidemiological studies, and to understand how drug resistance emerges and spreads. Here, we review the applications of the increasingly available genotyping tools and whole-genome sequencing data, and argue for a better integration of population genetics findings into malaria-control strategies.


Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1.
Neural crest cells form diverse derivatives that vary according to their level of origin along the body axis, with only cranial neural crest cells contributing to facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely expressed in cranial but not trunk neural crest, where it functions as a direct input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and interrogated a cis-regulatory element, conserved between birds and mammals, that drives reporter expression in a manner that recapitulates that of endogenous Ets-1 expression in the neural crest. Within a minimal Ets-1 enhancer region, mutation of putative binding sites for SoxE, homeobox, Ets, TFAP2 or Fox proteins results in loss or reduction of neural crest enhancer activity. Morpholino-mediated loss-of-function experiments show that Sox9, Pax7, Msx1/2, Ets-1, TFAP2A and FoxD3, all are required for enhancer activity. In contrast, mutation of a putative cMyc/E-box sequence augments reporter expression, consistent with this being a repressor binding site. Taken together, these results uncover new inputs into Ets-1, revealing critical links in the cranial neural crest gene regulatory network.


The effect of exposure to drugs on the processing of natural rewards.
Why does moderate exposure to a drug reward make natural rewards increasingly attractive to organisms, whereas prolonged exposure to the same drug reward has the opposite effect? The paradox behind that question remains unsatisfactorily captured by current theories of addiction. The incentive-sensitisation theory is viewed as a promising approach to this paradox, although it provides no mechanism to explain the decrease in interest of natural rewards as time exposure to a drug increases. To attempt to remedy this problem, I describe a model called the anticipatory dynamics model (ADM) that suggests a pivotal role of anticipation and attention in motivational interactions. In addition to relying on strong neuropsychopharmacological data, the ADM provides an original conception of motivational specificity. The ADM is an extension of the incentive-sensitisation theory that hypothesizes how drugs interact with natural rewards. It has not been tested empirically, although a possible experiment to test two predictions in the field of addiction is presented.


Deuterium magnetic resonance of triacylglycerols in phospholipid bilayers.
Aqueous dispersions of egg-phosphatidylcholine and egg-phosphatidylcholine/30 mol% cholesterol containing deuterated tripalmitin or triolein were studied at approx. 25 degrees C by 2H-NMR. Incorporation of tripalmitin into egg-phosphatidylcholine bilayers was found to be less than 0.1 mol%, while the incorporation of triolein is approx. 2.5 mol% in the absence and approx. 0.7 mol% in the presence of cholesterol. The profile of order parameter versus chain position for deuterated triolein suggests that the oleoyl chains of the triacylglycerol have an average orientation such that the C2 chain segments and the segments in the vicinity of the C9-C10 double bond are tilted with respect to the bilayer normal, while all other segments are parallel to the bilayer normal. Longitudinal relaxation times were also determined and indicate that the acyl chains of triolein have a motional behaviour similar to that of phospholipid acyl chains in the bilayer.


The role of ultrastructural investigations in neurotoxicology.
The ways in which ultrastructural approaches have been applied to the investigation of xenobiotic-induced toxicity of the nervous system have been briefly reviewed. These approaches have been grouped in 3 broad areas, viz. morphology, function and composition. Firstly, morphological approaches permit the visualisation of changes in intercellular relationships, the identification of the subcellular target(s) of a xenobiotic substance and the discrimination between what may appear ostensibly to be identical cellular responses to one or more chemically distinct toxins. Secondly, functional approaches using, e.g. cytochemistry, ion precipitation, immunocytochemistry and autoradiography provide indications of metabolic state, the identity or the intra- or extracellular location of the "reactive species". Thirdly, those approaches, viz. electronprobe X-ray microanalysis and electron energy loss spectroscopy which provide information of the elemental composition of cells and tissues permit an assessment of the subcellular distribution and compartmentalisation of endogenous substances and toxic or therapeutic xenobiotics. In concert, ultrastructural approaches possess the ability to contribute unique information on the effects of exposure of cells of the nervous system to toxic substances and so direct further investigation towards an understanding of the mechanism of action.


Stimuli to differentiate the neural response at successive stages of visual processing using the VEP from human visual cortex.
Clarifying the enigmatic relationship between stimulus property, neural response and the evoked potential is essential if non-invasive functional imaging is to make a meaningful contribution to the understanding of how maturational or degenerative processes influence brain activity. Visual cortex has proven a favourite target to elucidate this relationship. However, to date most studies involving the visual system have yielded inconsistent results or have been strongly criticised. We developed a set of three visual stimuli, two of which either had the same low- or high spatial frequency characteristic. Adult volunteers viewed these as pattern reversing stimuli while the scalp electric potential was recorded using a 10-10 array of electrodes. Established processing mechanisms of the primate visual system enabled us to link the amplitude of the N75 and P100 to the size of the neural population processing the temporal luminance contrast, and the amplitude of the N135 and P240 to the size of the neural processing the spatial luminance contrast in our stimuli. Calculating the distribution of current source density enabled us to identify the neural source of each VEP component. Demonstrating a direct relationship between the temporal- and spatial luminance contrast properties of our stimuli and the size of the neural population involved provides a better understanding of the nature of the relationship between stimulus property, neural response and the VEP. It also shows that EEG can contribute in a significant manner to the study of the influence of maturational or degenerative processes on brain activity.


Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I.
Xanthohumol is a prenylflavonoid extracted from hops (Humulus lupulus). It possesses anti-cancer and anti-inflammatory activities in vitro and in vivo, and offers therapeutic benefits for treatment of metabolic syndromes. However, the precise mechanisms underlying its pharmacological effects remain to be elucidated, together with its cellular target. Here, we provide evidence that xanthohumol directly interacts with the mitochondrial electron transfer chain complex I (NADH dehydrogenase), inhibits the oxidative phosphorylation, triggers the production of reactive oxygen species, and induces apoptosis. In addition, we show that as a result of the inhibition of the mitochondrial oxidative phosphorylation, xanthohumol exposure causes a rapid decrease of mitochondrial transmembrane potential. Furthermore, we showed that xanthohumol up-regulates the glycolytic capacity in cells, and thus compensates cellular ATP generation. Dissection of the multiple steps of aerobic respiration by extracellular flux assays revealed that xanthohumol specifically inhibits the activity of mitochondrial complex I, but had little effect on that of complex II, III and IV. Inhibition of complex I by xanthohumol caused the overproduction of reactive oxygen species, which are responsible for the induction of apoptosis in cancer cells. We also found that isoxanthohumol, the structural isomer of xanthohumol, is inactive to cells, suggesting that the reactive 2-hydroxyl group of xanthohumol is crucial for its targeting to the mitochondrial complex I. Together, the remodeling of cell metabolism revealed here has therapeutic potential for the use of xanthohumol.


Peritoneolysis in the reconstruction of the Roux-en-Y loop.
A technique to provide an additional 5 centimeters of length, without compromising the blood supply to the anastomosis, was developed. It has been applied to 26 patients, 18 with Roux-en-Y biliary bypass at various levels, five with high Roux-en-Y esophagojejunostomies and three with gastrojejunostomies. In the last three patients with unresectable adenocarcinoma of the distal part of the stomach and invasion of the intestinal mesentery, due to foreshortening of the latter, the proximal loop of the intestine would not reach the desired level of the stomach until this maneuver was performed.


Annular management during aortic valve repair: a systematic review.
Annuloplasty is considered to play a key role to control aortic valve regurgitation (AR) and prevent recurrence of AR after aortic valve repair, because aortic root dilatation has emerged as a risk factor for recurrence of AR. Various modifications of annuloplasty have been advocated, however, none of them has become standardized. Thus in this review they are outlined and classified (internal/external, with/without ring, rigid/flexible ring), and their advantages and disadvantages are clarified. Their clinical outcomes seem currently acceptable in general, and external flexible annuloplasty has been performed more frequently with favorable outcomes. However, they are still performed for a minority of patients by special experienced teams with limited follow-up periods. Therefore, it seems too early to determine the superiority or inferiority of each approach. We must carefully conduct evaluation to clarify which approach will become reproducible, effective, and standardized.


Development of Upper-Extremity Morphological Asymmetries in Male and Female Elite Youth Tennis Players: A Longitudinal Study.
This 2-year longitudinal study examined the development of upper-extremity bone mineral density (BMD), bone mineral content (BMC), and lean mass (LM) asymmetry magnitudes in male and female youth tennis players. Dominant and nondominant upper-extremity BMD, BMC, and LM values of 49 male and 31 female players were measured yearly using dual X-ray absorptiometry. From these values, asymmetry magnitudes were calculated and expressed as a percentage. Maturity offset was estimated using anthropometric measurements. Linear mixed effect models examined the development of BMD, BMC, and LM asymmetry magnitudes according to players' maturity offset, sex, and training volume. Adjusted for sex and training volume, a 1-year increment in maturity offset was associated with a significant increase in BMD (1.3% [2.2%]; P < .001) and BMC (0.6% [2.4%]; P = .011) asymmetry magnitudes. Male players displayed significantly higher LM asymmetry magnitudes (Δ3.2% [8.4%]; P = .002) compared with their female counterparts. Training volume was not significantly associated with asymmetry magnitude development. In contrast to LM, male and female youth tennis players' upper-extremity bones are still responsive to mechanical loading with a significant increase in BMD and BMC asymmetry magnitudes according to maturity offset.


1-Acyl-3-0-[β-glucopyranosyl-(1"-+ 6')-β-glucopyranosyl]-glycerols and Cordycedipeptides B and C, New Metabolites from Bacillus pumilus.
Four 1-monoacyl-3-0-[β-glucopyranosyl-( ->6)-β-glucopyranosyl]-glycerols (1) and four 1,2-diacyl-3-0-[p-glucopyranosyl-(1->6)-p-glucopyranosyl]- glycerols (2a) with acyl residues consisting of 1:1 mixtures of 1-iso-pentadecanoyl- and 1 -anteiso-pentadecanoyl residues and the respective heptadecanoic acid isomers s as main components, have been characterized in the extracts of Bacillus pumilus strain DKS 1. Twenty-seven further metabolites, among them the diketopiperazines cordycedipeptide A (3), B (4), and C (5), were obtained. All compounds were elucidated by NMR and MS techniques and fully characterized and tested for antimicrobial activity against Legionella pneumophila.


Qingluotongbi formula regulates the LXRα-ERS-SREBP-1c pathway in hepatocytes to alleviate the liver injury caused by Tripterygium wilfordii Hook. f.
Tripterygium wilfordii Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases; however, its development and application is limited by its significant association with liver injury. The compound formula Qingluotongbi (QLT) employs TW as its main component and is used to treat rheumatoid arthritis with no adverse reactions, suggesting that QLT may reduce the liver toxicity of TW. We examined whether TW interferes with lipid metabolism to induce liver injury, and evaluated the protective effect of QLT in in vivo and in vitro experiments. After administration of QLT and its ingredients, HepaRG cells and SD rats were tested for biochemical indicators, hepatocytes lipid changes, and rat liver pathological changes, and then we analyzed for the gene expression of liver X receptor α (LXRα), endoplasmic reticulum stress (ERS) key proteins, sterol regulatory element binding protein-1c (SREBP-1c), and lipid-synthesizing enzymes. In HepaRG cells, the protein expression of glucose-regulated protein 78 kDa (GRP78) and LXRα was detected after addition of an LXRα inhibitor, LXRα agonist, and ERS inhibitor. TW caused significant elevation of biochemical indicators and lipid droplet deposition in hepatocytes, as well as upregulated the gene expression of LXRα, ERS key proteins, SREBP-1c, and lipid-synthesizing enzymes in both in vitro and in vivo settings, and caused liver injury in rats. QLT can alleviate the lipotoxic liver injury caused by TW. LXRα agonist further activated ERS induced by TW, whereas LXRα inhibitor significantly reduced ERS and lipotoxic injury induced by TW in HepaRG cells. TW upregulated LXRα to activate ERS and increased the gene expression of SREBP-1c and lipid-synthesizing enzymes, leading to increased lipid synthesis in hepatocytes to result in liver injury. QLT inhibited the LXRα-ERS-SREBP-1c pathway and reduced abnormal lipid synthesis in hepatocytes and the hepatotoxicity of TW.


Development of an information system and mobile application for the care of type 2 diabetes patients at the primary care level for the health sector in Mexico: study protocol for a randomized controlled, open-label trial.
Providing optimal care for type 2 diabetes (DM2) patients remains a challenge for all healthcare systems. Patients often encounter various barriers in adhering to self-management programs due to lack of knowledge and understanding of self-care activities, lack of individualized and coordinated care, inconvenient and costly education sessions, and poor patient-provider communication. Mobile technologies such as cell phones/smartphones, handheld tablets, and other wireless devices offer new and exciting opportunities for addressing some of these challenges. The purpose of this study is to compare a diabetes management strategy using an information board and a mobile application versus standard care in patients with uncontrolled DM2. The SANENT (Sistema de Análisis de Enfermedades No Transmisibles) trial is a primary care-based, prospective, two-arm, randomized controlled, open-label, blinded-endpoint study. We aim to recruit 1440 DM2 patients during a period of 6 months until the requested number of participants has been achieved. The total length of the intervention will be 1 year. Both men and women treated for DM2 with an HbA1c > 8.5% and ≥ 20 years of age are eligible to participate in the study. The primary outcome of the study is improved diabetes control measured by changes in HbA1c in the study participants. HbA1c will be measured at baseline, 3-month, 6-month, 9-month, and 12-month follow-up visits in all participants. The main analysis will be based on the intention-to-treat principle. The primary endpoint of the study will be the change in HbA1C within the groups and the differences between the groups. This will be assessed by a repeated measurement approach based on mixed models which contain both fixed effects and random effects. The overall goal of this project is to contribute to the evidence for the use of mobile technology to improve the treatment and regulation of poorly controlled DM2 patients living in Mexico. Our proposed project will show how mobile health technology tools can be used in the treatment of patients with uncontrolled DM2 in primary health care in a Latin American population, and particularly how they could help diabetes patients take better care of themselves. ClinicalTrials.gov , US National Institutes of Health NCT04974333 . Prospectively registered on July 13, 2021. Protocol version number 1, dated August 15th, 2021.


Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.
The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.


Computational analyses of the length and compositional variations of the FNBP4 gene across 10 different species.
Formin binding protein 4 (FNBP4) interacts with formins and other proteins via its WW domains. Previously, we reported the structural and phylogenetic clustering of FNBP4 across a wide range of organisms from different taxonomic groups along with characterizing its plant variant (Arabidopsis thaliana F4JC80). Recently, the FNBP4 gene is reported to be associated with a congenital disorder Microphthalmia with Limb Anomalies. Except these reports, FNBP4 is mostly uncharacterized, especially the FNBP4 gene. In this context, we have attempted to characterize the FNBP4 gene in terms of its length and compositional variations across 10 different organisms from different taxonomic groups. Our findings highlight that the length of the FNBP4 gene varies greatly among different species. Introns, UTRs and the entire gene were AT rich while CDS and mRNAs were GC rich. The RSCU values were also different for the different organisms indicating a possible impact on translational efficiency of this protein. Comparative analyses highlight gene element and base proportions related characteristics specific to highly expression regulated genes like FNBP4.


Comparative uptake, vascular transport, and cellular internalization of aflatoxin-B1 and benzo(a)pyrene.
Studies of the uptake of benzo(a)pyrene (BaP) and aflatoxin-B1 (AFB1) after gastric instillation showed that BaP was absorbed via the intestinal lymphatic drainage and transported to the vascular circulation sequestered within lipoproteins in thoracic duct lymph, while AFB1 was absorbed with water soluble compounds into the gastrointestinal venous drainage and was not transported in association with lipoproteins. BaP was taken up into plasma lipoproteins over a broad concentration range, while AFB1 was not sequestered within lipoproteins over the same concentration range. Low density lipoproteins (LDL) facilitated BaP uptake into fibroblasts and impeded BaP uptake into hepatocytes. High density lipoproteins (HDL) facilitated BaP uptake into hepatocytes and impeded BaP uptake into fibroblasts. The uptake of AFB1 into either fibroblasts or hepatocytes was not affected by lipoproteins.


Metabolic Regulation of Inflammasome Activity Controls Embryonic Hematopoietic Stem and Progenitor Cell Production.
Embryonic hematopoietic stem and progenitor cells (HSPCs) robustly proliferate while maintaining multilineage potential in vivo; however, an incomplete understanding of spatiotemporal cues governing their generation has impeded robust production from human induced pluripotent stem cells (iPSCs) in vitro. Using the zebrafish model, we demonstrate that NLRP3 inflammasome-mediated interleukin-1-beta (IL1β) signaling drives HSPC production in response to metabolic activity. Genetic induction of active IL1β or pharmacologic inflammasome stimulation increased HSPC number as assessed by in situ hybridization for runx1/cmyb and flow cytometry. Loss of inflammasome components, including il1b, reduced CD41+ HSPCs and prevented their expansion in response to metabolic cues. Cell ablation studies indicated that macrophages were essential for initial inflammasome stimulation of Il1rl1+ HSPCs. Significantly, in human iPSC-derived hemogenic precursors, transient inflammasome stimulation increased multilineage hematopoietic colony-forming units and T cell progenitors. This work establishes the inflammasome as a conserved metabolic sensor that expands HSPC production in vivo and in vitro.


A Zr(IV)-based porphyrinic metal-organic framework as a solid-phase sorbent for extraction of sulfonamides prior to their quantitation by LC-MS.
A porphyrinic metal-organic framework (PCN-224) was fabricated and used as an adsorbent for solid-phase extraction of ultratrace levels of polar sulfonamide antibiotics from food and drinking waters. The PCN-224 was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and powder X-ray diffraction analyses. Parameters affecting the extraction efficiency were optimized. The sulfonamides were quantified by liquid chromatography-tandem mass spectrometry. Figures of merit include (a) low limits of detection (0.07-0.47 ng·L-1), (b) wide linear ranges (0.5-2000 ng·L-1), and (c) good repeatabilities (2.8%-6.7%) and reproducibilities (1.7%-5.1%). The method was successfully applied to the determination of sulfonamides in food and drinking water samples. Graphical abstract A Zr(IV)-based porphyrinic metal-organic framework (PCN-224) was synthesized from a Zr6 cluster and the H2TCPP ligand. It was used for solid-phase extraction of sulfonamides from food and drinking water samples coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination.


Exploring perceived barriers to effective utilization of learner-centred teaching methods by tutors at Holy Family College of Nursing and Midwifery, Phalombe, Malawi.
Learner-centred teaching implies a paradigmatic shift in roles of a teacher from being a source of knowledge to that of a facilitator in the process of knowledge construction. Literature shows that perceptions which teachers hold about barriers to utilisation of learner-centred teaching methods influence how the teachers teach. Anecdotal records as well as observation of classroom teaching demonstrate that tutors at Holy Family College of Nursing and Midwifery dominantly use traditional teacher-centred teaching methods. This was a qualitative study based on the philosophical principle of constructivism. All tutors at Holy Family College of Nursing and Midwifery were the study population. Purposive sampling technique was used to select participants. In-depth interviews with 12 tutors were held using a semi-structured interview guide. Data were analysed using the 6-step thematic method. The participants suggested that effective utilization of learner-centred teaching methods is negatively affected by teacher-related as well as technical barriers. Teachers clinging to power and need for more resources negatively affect utilisation of learner-centred teaching methods.


Determinants of the clinical outcome of patients with severe acute exacerbation of chronic hepatitis B virus infection.
Severe acute exacerbation of chronic hepatitis B can sometimes occur and lead to hepatic failure and death. The objective of this study was to elucidate the predictors of progression to hepatic decompensation during severe acute exacerbation. We prospectively analyzed 37 consecutive patients with acute exacerbation of chronic hepatitis B (accompanied by jaundice and coagulopathy) for clinical outcome and factors that influenced the development of severe acute exacerbation, including viral kinetics. Fourteen (37.8%) patients progressed to severe acute exacerbation (accompanied by encephalopathy). Multivariate analysis identified serum bilirubin (>5 mg/dl, P = 0.002) as a significant determinant of progression to hepatic failure and prothrombin activity (<45%, P = 0.028) and as a determinant of liver-related death. The hepatitis B virus (HBV) DNA level before therapy was measured in 25 patients. HBV DNA levels increased or did not change from before commencement of treatment in all 11 patients who progressed to severe acute exacerbation. On the other hand, HBV DNA levels did not change or increased in 8 of 14 patients (57%) with acute exacerbation (P = 0.02). Serum bilirubin and prothrombin activities were significant predictors of clinical outcome in patients with severe acute exacerbation of chronic hepatitis B. Viral kinetics until commencement of therapy can predict the severity of acute exacerbation of chronic hepatitis B.


Fish apolipoprotein-A-I has heparin binding activity: implication for nerve regeneration.
This study provides evidence that apolipoprotein-A-I (apo-A-I), derived from fish plasma and nerve, has heparin binding activity. We have shown previously that injury in a regenerative CNS, such as that of fish optic nerves, leads to increased levels of apo-A-I in media conditioned by these nerves, as compared with media conditioned by noninjured nerves. In the present study, we have purified and characterized apo-A-I from both fish plasma and optic nerves. Sequence analysis of the 15 N-terminal amino acids revealed that at least 14 amino acids are identical in these two purified apo-A-I samples. The purified apo-A-I derived from both fish plasma and optic nerves binds to heparin. Binding measurements using [3H]heparin followed by Scatchard analysis revealed that apo-A-I binds to heparin with relatively low affinity (KD = 2.8 x 10(-6) M). Results are discussed with respect to the possibility that accumulation of apo-A-I in the extracellular matrix of fish optic nerves is made possible via heparin binding, like that to apolipoprotein-E in mammals.


Genetic analysis as a tool for prediction of mycotoxin-producing Fusarium strains.
The formation of fertile crosses (when possible), nuclear DNA relatedness and sequence comparison of select region of a large subunit (25S) ribosomal RNA are suitable methods for taxonomic determination and a phylogenetic classification of the strains. These genetic methods can also be used to predict whichFusarium strains produce mycotoxins since the genetic placement of the strains has been shown to have a good correlation with mycotoxin production ability at the species level.


The dynamics of changing internal jugular veins diameter based on increasing head elevation angle.
Venous outflow from the cranial cavity occurs mainly through the internal jugular vein (IJV). The increase in venous outflow through IJV is possible by head elevation. IJV collapse may indicate the reduction of blood volume in the vein and show the head elevation effectiveness. The aim of this study is to examine the impact of head elevation on IJV size. IJV ultrasound scanning in 31 healthy volunteers was carried after gradual head elevation at 15°, 30°, and 45°. Maximum and minimum IJV diameters were recorded. Mean ± standard deviation, median, range, and collapsibility index were calculated. Thirty-one volunteers were involved (19 males), their average age was 37.0 ± 11.5 years. Increasing the head elevation angle by 15°, 30° and 45° resulted in a decrease in IJV diameter in the right and left sides in all patients. The occurrence of the vein walls collapse corresponds to the collapsibility index equal to 100%. The results showed that 100% collapsibility index was recorded in 6 patients (19%) at 15° head elevation, in 12 patients (39%) at 30°, in 11 patients (35%) at 45°. In two volunteers (6%), 100% collapsibility index was not recorded even at maximum 45° head elevation. Ultrasound IJV scanning during gradual head elevation together with the collapsibility index calculation could be useful guidance for the venous outflow assessment. In order to prove and extend the study findings, more research is needed.


An unusual presentation of a mixed epithelial and stromal tumor in an elderly male.
Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms characterized by mixed cystic and solid components. These tumors are typically present in middle-aged women as a flank mass, or as a cause of flank pain or hematuria. We outline the case of an older male who presented with an enlarging abdominal mass causing symptoms that suggested a partial small bowel obstruction. Management of the patient and a brief review are discussed.


Should the 'normal' and 'ideal' nipple position in a male influence the surgeon when planning severe gynaecomastia correction?
The ideal nipple areolar complex (NAC) position of the male chest following gynaecomastia surgery is well documented; however, with increased development of the chest muscles, the NAC placement can change, leading to the medial displacement of the nipple giving a poor aesthetic outcome. Therefore, we believe that these measurements need to be applied to the patients' build and take into consideration the future fitness goals of the patients. We have analysed the photographs of three groups of men: super athletes, athletes and individuals with severe gynaecomastia. We have assessed the proportions of the chest in relation to the NAC, degree of ptosis and TAP index. There was a wide variation between the athlete and the super athlete group, with minor variations within each group. The range of measurement in the severe gynaecomastia group was significantly larger than those in the other groups. We feel that based on this research study, surgeons should however be somewhat circumspect in their choice of nipple position as there is a wide variation in what can be considered as normal, and positioning of the NAC too early in the recovery process may lead to an abnormal aesthetic appearance following muscle development. Despite the multitude of techniques available in the literature to determine the position of nipple, there is a lack of understanding on how the NAC position changes with muscle development. Adopting a dogmatic approach may result in a very aesthetically displeasing outcome, which can be very difficult to correct in men.


cDNA cloning and structure of mouse putative Ah receptor.
Mouse cDNA clones for a putative Ah receptor have been isolated from a cDNA library of mRNA from Hepa-1 cells by an oligonucleotide probe produced by PCR with a pair of primers which was synthesized according to the reported N-terminal sequence of 26 amino acids. The cDNA clones encode a polypeptide of 805 amino acids with a helix-loop-helix motif and with some similarity to a certain region designated PAS of Drosophila Per and Sim, and human Arnt protein. Cotransfection of an expression vector of the Ah receptor with a reporter plasmid pMC6.3k consisting of CYP1A1 promoter and CAT structural gene into CV-1 cells enhanced the CAT expression in response to added 3-methylcholanthrene.


Escape of leukemia blasts from HLA-specific CTL pressure in a recipient of HLA one locus-mismatched bone marrow transplantation.
A case of leukemia escape from an HLA-specific cytotoxic T lymphocyte (CTL) response in a recipient of bone marrow transplantation is presented. Only the expression of HLA-B51, which was a mismatched HLA locus in the graft-versus-host direction, was down-regulated in post-transplant leukemia blasts compared with that in pre-transplant blasts. All CTL clones, that were isolated from the recipient's blood when acute graft-versus-host disease developed, recognized the mismatched B(∗)51:01 molecule in a peptide-dependent manner. The pre-transplant leukemia blasts were lysed by CTL clones, whereas the post-transplant leukemia blasts were not lysed by any CTL clones. The IFN-γ ELISPOT assay revealed that B(∗)51:01-reactive T lymphocytes accounted for the majority of the total alloreactive T lymphocytes in the blood just before leukemia relapse. These data suggest that immune escape of leukemia blasts from CTL pressure toward a certain HLA molecule can lead to clinical relapse after bone marrow transplantation.


Binding versus Enzymatic Processing of ε-Trimethyllysine Dioxygenase Substrate Analogues.
ε-Trimethyllysine dioxygenase (TMLD) is a non-heme Fe(II) and α-ketoglutarate dependent oxygenase that catalyzes the stereospecific hydroxylation of ε-trimethyl-l-lysine (TML) to β-hydroxy-TML during the first step of l-carnitine biosynthesis. Targeting TMLD with inhibitors is a viable strategy for the treatment of cardiovascular diseases. Herein, we report a methodology for isothermal titration calorimetry analysis of TMLD substrate analogue binding to the enzyme. Despite the high structural similarity of the tested compounds, two different binding mechanisms (enthalpy- and entropy-driven) were observed, giving insight into the ligand (substrate) selectivity of TMLD. We demonstrate that the method allows distinguishing a natural substrate-like binding mode, which correlates with the ability of the compounds to serve as substrates in the TMLD catalytic reaction.


Addressing Adverse Childhood and Adult Experiences During Prenatal Care.
Adverse childhood and adult experiences can affect health outcomes throughout life and across generations. The perinatal period offers a critical opportunity for obstetric clinicians to partner with patients to provide support and improve outcomes. This article draws on stakeholder input, expert opinion, and available evidence to provide recommendations for obstetric clinicians' inquiry about and response to pregnant patients' past and present adversity and trauma during prenatal care encounters. Trauma-informed care is a universal intervention that can proactively address adversity and trauma and support healing, even if a patient does not explicitly disclose past or present adversity. Inquiry about past and present adversity and trauma provides an avenue to offer support and to create individualized care plans. Preparatory steps to adopting a trauma-informed approach to prenatal care include initiating education and training for practice staff, prioritizing addressing racism and health disparities, and establishing patient safety and trust. Inquiry about adversity and trauma, as well as resilience factors, can be implemented gradually over time through open-ended questions, structured survey measures, or a combination of both techniques. A range of evidence-based educational resources, prevention and intervention programs, and community-based initiatives can be included within individualized care plans to improve perinatal health outcomes. These practices will be further developed and improved by increased clinical training and research, as well as through broad adoption of a trauma-informed approach and collaboration across specialty areas.


Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers.
Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived "healthy" normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact "differential" expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.


CRISPR/Cas9-mediated simultaneous mutation of three salicylic acid 5-hydroxylase (OsS5H) genes confers broad-spectrum disease resistance in rice.
Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5-hydroxylase (S5H) in rice-pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5-hydroxylase activity, converting SA into 2,5-dihydroxybenzoic acid (2,5-DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5-DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9-mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis-related (PR) genes. Besides, flg22-induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad-spectrum disease resistance through OsS5H gene editing.


Structural changes in caudate nucleus, cerebral cortex and hippocampus induced by morphine. Light microscopy study.
Intraperitoneal chronic morphine administration to rats produced structural alterations in nerve cells of caudate nucleus, cerebral cortex and hippocampus. All areas studied showed increased alterations related to time elapsed between last morphine injection and fixation of tissue samples. Lesions mainly consisted in vacuolar degeneration of nerve cells. The most extense and intense lesions were observed in hippocampus. Sensorimotor cortex and caudate nucleus showed focal damage. Neurocytotoxic effect of morphine appears to be unrelated to the opiate receptor density in brain areas, and the brain regions susceptible to that effect appears to be different from brain areas related to adaptation to morphine. Effect of morphine on integrity and function of nerve cells mitochondria, interfering with energy production could play an important role in the pathogenesis of neuronal lesions.


Artifacts in oral biopsy specimens.
More than proper surgical technique is required to facilitate the proper diagnosis of an oral biopsy specimen. The proper preparation of the tissue for microscopic analysis depends on steps taken by the surgeon, assistant, and histotechnician to reduce the inclusion of artifacts. There are many ways that the exact interpretation of tissue specimens can be compromised. Unfortunately, many practitioners seem to be unaware of the extent of this problem, as well as how easily artifacts can be prevented.


Thiosulfate pretreatment enhancing short-chain fatty acids production from anaerobic fermentation of waste activated sludge: Performance, metabolic activity and microbial community.
A novel strategy based on thiosulfate pretreatment for enhancing short-chain fatty acids (SCFAs) from anaerobic fermentation (AF) of waste activated sludge (WAS) was proposed in this study. The results showed that the maximal SCFA yield increased from 206.1 ± 4.7 to 1097.9 ± 17.2 mg COD/L with thiosulfate dosage increasing from 0 to 1000 mg S/L, and sulfur species contribution results revealed that thiosulfate was the leading contributor to improve SCFA yield. Mechanism exploration disclosed that thiosulfate addition largely improved WAS disintegration, due to thiosulfate serving as a cation binder for removing organic-binding cations, especially Ca2+ and Mg2+, dispersing the extracellular polymeric substance (EPS) structure and further entering into the intracellularly by stimulated carrier protein SoxYZ and subsequently caused cell lysis. Typical enzyme activities and related functional gene abundances indicated that both hydrolysis and acidogenesis were remarkably enhanced while methanogenesis was substantially suppressed, which were further strengthened by the enriched hydrolytic bacteria (e.g. C10-SB1A) and acidogenic bacteria (e.g. Aminicenantales) but severely reduced methanogens (e.g. Methanolates and Methanospirillum). Economic analysis confirmed that thiosulfate pretreatment was a cost-effective and efficient strategy. The findings obtained in this work provide a new thought for recovering resource through thiosulfate-assisted WAS AF for sustainable development.


Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia.
Available literature documents that ischemic stroke can disrupt the morphology and function of mitochondria and that the latter in other disease models can be preserved by neuropilin-1 (NRP-1) via oxidative stress suppression. However, whether NRP-1 can repair mitochondrial structure and promote functional recovery after cerebral ischemia is still unknown. This study tackled this very issue and explored the underlying mechanism. Adeno-associated viral (AAV)-NRP-1 was stereotaxically inoculated into the cortex and ipsilateral striatum posterior of adult male Sprague-Dawley (SD) rats before a 90-min transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion. Lentivirus (LV)-NRP-1 was transfected into rat primary cortical neuronal cultures before a 2-h oxygen-glucose deprivation and reoxygenation (OGD/R) injury to neurons. The expression and function of NRP-1 and its specific protective mechanism were investigated by Western Blot, immunofluorescence staining, flow cytometry, magnetic resonance imaging, transmission electron microscopy, etc. The binding was detected by molecular docking and molecular dynamics simulation. Both in vitro and in vivo models of cerebral ischemia/reperfusion (I/R) injury presented a sharp increase in NRP-1 expression. The expression of AAV-NRP-1 markedly ameliorated the cerebral I/R-induced damage to the motor function and restored the mitochondrial morphology. The expression of LV-NRP-1 alleviated mitochondrial oxidative stress and bioenergetic deficits. AAV-NRP-1 and LV-NRP-1 treatments increased the wingless integration (Wnt)-associated signals and β-catenin nuclear localization. The protective effects of NRP-1 were reversed by the administration of XAV-939. NRP-1 can produce neuroprotective effects against I/R injury to the brain by activating the Wnt/β-catenin signaling pathway and promoting mitochondrial structural repair and functional recovery, which may serve as a promising candidate target in treating ischemic stroke.


Purification and characterization of a beta-1,3-glucan binding protein from plasma of the crayfish Pacifastacus leniusculus.
The plasma of the crayfish Pacifastacus leniusculus contains a protein which is able to bind to laminarin (a soluble beta-1,3-glucan) and which has been isolated by two independent methods, affinity precipitation with a beta-1,3-glucan or immunoaffinity chromatography. The purified beta-1,3-glucan binding protein was homogenous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a monomeric glycoprotein with a molecular mass of approximately 100,000 Da and an isoelectric point of approximately 5.0. Amino acid analysis showed a very high similarity with the amino acid composition of beta-1,3-glucan binding proteins recently purified from two insects, the cockroach Blaberus craniifer and the silkworm Bombyx mori. The N-terminal amino acid sequence was determined to be: H2N-Asp-Ala-Gly-X-Ala-Ser-Leu-Val-Thr-Asn-Phe-Asn-Ser-Ala-Lys-Leu-X-X-Ly s--- Using monospecific rabbit polyclonal antibodies, the presence of this protein has also been shown within the blood cells. The purified beta-1,3-glucan binding protein did not show any peptidase or phenoloxidase activity but was able to enhance the activation of hemocyte-derived peptidase and prophenoloxidase only in the presence of the beta-1,3-glucan, laminarin, whereas mannan, dextran (alpha-glucan), or cellulose (beta-1,4-glucan) incubated with the beta-1,3-glucan binding protein had no effect on these enzyme activities. The beta-1,3-glucan binding protein could only be affinity-precipitated from crayfish plasma by the beta-1,3-glucans laminarin or curdlan (an insoluble beta-1,3-glucan), while mannan or dextran did not bind to the beta-1,3-glucan binding protein. No hemagglutinating activity of the purified beta-1,3-glucan binding protein could be detected.


Small mosquitoes, large implications: crowding and starvation affects gene expression and nutrient accumulation in Aedes aegypti.
Environmental factors such as temperature, nutrient availability, and larval density determine the outcome of postembryonic development in mosquitoes. Suboptimal temperatures, crowding, and starvation during the larval phase reduce adult mosquito size, nutrient stores and affect vectorial capacity. In this study we compared adult female Aedes aegypti, Rockefeller strain, raised under standard laboratory conditions (Large) with those raised under crowded and nutritionally deprived conditions (Small). To compare the gene expression and nutritional state of the major energy storage and metabolic organ, the fat body, we performed transcriptomics using Illumina based RNA-seq and metabolomics using GC/MS on females before and 24 hours following blood feeding. Analysis of fat body gene expression between the experimental groups revealed a large number of significantly differentially expressed genes. Transcripts related to immunity, reproduction, autophagy, several metabolic pathways; including amino acid degradation and metabolism; and membrane transport were differentially expressed. Metabolite profiling identified 60 metabolites within the fat body to be significantly affected between small and large mosquitoes, with the majority of detected free amino acids at a higher level in small mosquitoes compared to large. Gene expression and metabolites in the adult fat body reflect the individual post-embryonic developmental history of a mosquito larva. These changes affect nutritional storage and utilization, immunity, and reproduction. Therefore, it is apparent that changes in larval environment due to weather conditions, nutrition availability, vector control efforts, and other factors can affect adult vectorial capacity in the field.


The conduction system in the human heart at midgestation--immunohistochemical demonstration of the intermediate filament protein skeletin.
The intermediate filaments have during recent years increasingly attracted attention and new information on the distribution of the subunits of the filaments has become available by the use of specific antibodies. In the present study human fetal hearts at midgestation were studied with immunofluorescence microscopy for a demonstration of the intermediate filament subunit skeletin. In the ordinary ventricular and atrial myocytes the fluorescence was moderate, mainly concentrated to the Z disk levels. The proximal parts of the conduction system also showed a moderate fluorescence, while the fluorescence was intense in the cells in the peripheral parts. The shift from moderate to intense fluorescence occurred in the very proximal part of the left bundle branch and in the distal part of the intramural right bundle branch. We conclude that the conduction cells attain Purkinje fibre-like characteristics at these levels, as evidenced by the content of skeletin. Furthermore, the human fetal Purkinje fibres are more easily distinguished with the technique used herein than with conventional histological techniques. The observed differences in content of skeletin are discussed in terms of the cytoskeletal function of intermediate filaments and the embryology of the conduction system.


Impact of Right Ventricular Surface Area-to-Volume Ratio on Ventricular Remodeling After Pulmonary Valve Replacement.
Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR. Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48%) vs. suboptimal remodeling (EDVi ≥ 120 ml/m2 and EF ≤ 45%). RV geometry was markedly different at baseline in PVR patients compared with controls, with lower systolic surface area-to-volume ratio (SAVR) (1.16 ± 0.26 vs.1.44 ± 0.21 cm2/mL, p < 0.001) and lower systolic circumferential curvature (0.87 ± 0.27 vs. 1.07 ± 0.30 cm- 1, p = 0.007) but similar longitudinal curvature. In the PVR cohort, higher systolic SAVR was associated with higher RVEF both pre- and post-PVR (p < 0.001). Among PVR patients, 15 had optimal and 19 had suboptimal remodeling post-PVR. Multivariable modeling showed that among the geometric parameters, higher systolic SAVR (OR 1.68 per 0.1 cm2/mL increase; p = 0.049) and shorter systolic RV long-axis length (OR 0.92 per 0.1 cm increase; p = 0.035) were independently associated with optimal remodeling. Compared with controls, PVR patients have lower SAVR and lower circumferential but not longitudinal curvature. Higher pre-PVR systolic SAVR is associated with optimal remodeling post-PVR.


Effects of diabetes and vascular occlusion on adenosine-induced relaxant response of rat common carotid artery.
The aim of this study was to investigate effect of adenosine on isolated rat common carotid artery (CA) submitted to occlusion in non-diabetic or diabetic animals, and to determine whether endothelium denudation or potassium conductance block affects adenosine action. Experiments were conducted on Wistar rat CA with or without endothelium. Diabetes was induced by alloxan. Occlusion of CA was performed in randomly selected non-diabetic or diabetic animals anesthetized with urethane. Thus, experiments were performed in four groups of rats: non-operated (control) animals without or with diabetes and operated animals submitted to the occlusion of CA without or with diabetes. Concentration-response curves for adenosine were obtained in a cumulative fashion on precontracted arteries. Adenosine produced concentration-dependent and endothelium-independent relaxation of CA with comparable maximal effects in all groups. Analysis of pEC50 values showed that responsiveness of CA decreased in following order: [diabetes (-) / occlusion (-)] = [diabetes (-) / occlusion (+)] > [diabetes (+) / occlusion (-)] > [diabetes (+) / occlusion (+)]. In the presence of high K(+) maximal relaxant response of CA from non-operated rats without diabetes was reduced. The recorded inhibition was even stronger in animals subjected to CA occlusion. Conversely, in non-operated diabetic animals obtained reduction of adenosine effect was less pronounced in regard to non-diabetic rats. Adenosine produced equi-effective endothelium-independent relaxation of CA in all groups. Pharmacological potency of adenosine was reduced in diabetic animals solely, but even more in diabetic rats submitted to CA occlusion. The enhanced potassium transmembrane flow has certain protective role on adenosine-induced action in occluded CA from non-diabetic rats. Conversely, diabetes solely inhibited adenosine-evoked cascade connected to increased potassium conductance.


MRI of patellar articular cartilage: evaluation of an optimized gradient echo sequence (3D-DESS).
Our purpose was to evaluate the diagnostic efficacy of a gradient-echo sequence optimized for cartilage imaging in patellar cartilage abnormalities and to compare it to a standard turbo-spin-echo sequence. Fifty-eight consecutive patients who underwent, within 3 months both MRI and arthroscopy or surgery, were included in the investigation. Two radiologists specializing in musculoskeletal imaging independently assessed axial three-dimensional double-echo steady state (3D-DESS) gradient-echo images and sagittal proton- and T2-weighted turbo-spin-echo images with regard to retropatellar cartilage abnormalities. Possible findings were: 0: normal, 1: cartilage softening, and 2: lesion of the articular surface. Inter- and intraobserver variability was assessed. For cartilage softening, the axial 3D-DESS sequence had a sensitivity of 73%, a specificity of 75%, and an accuracy of 70%. The corresponding results for the sagittal turbo-spin-echo sequence were 53%, 65%, and 62%. For surface lesions, the results for the 3D-DESS sequence were 43%, 92%, and 83% and for the turbo-spin-echo sequence were 60%, 92%, and 86%. Intra- and interobserver agreement was moderate (k = 0.59 and 0.45 [DESS], 0.6 and 0.46 [turbo -spin-echo]). We conclude that the 3D-DESS sequence is moderately accurate in detecting patellar cartilage abnormalities. Compared with the sagittal turbo-spin-echo sequence, the axial 3D-DESS sequence is superior in diagnosing cartilage softening but not surface lesions.


High prevalence of sensitization to gibberellin-regulated protein (peamaclein) in fruit allergies with negative immunoglobulin E reactivity to Bet v 1 homologs and profilin: Clinical pattern, causative fruits and cofactor effect of gibberellin-regulated protein allergy.
Gibberellin-regulated protein (GRP) is a new allergen in peach allergy, with an amino acid sequence very well conserved through several botanical species. We investigated the allergenicity of GRP in fruit allergies other than peaches and identified the clinical characteristics of fruit allergy patients with GRP sensitization. One hundred consecutive Japanese patients with fruit allergies were enrolled in the present study. To identify the features of GRP sensitization, we selected patients with negative ImmunoCAP results for Bet v 1 homologs and profilin, which are marker allergens for pollen-food allergy syndrome (PFAS), or lipid transfer protein. These patients underwent specific immunoglobulin E measurements by enzyme-linked immunosorbent assay (ELISA) and skin prick tests (SPT) using purified nPru p 7. Twenty of 100 consecutive patients with fruit allergies had negative ImmunoCAP results for Bet v 1 homologs and profilin. Thirteen (65.0%) of the 20 patients had positive ELISA and/or SPT results using nPru p 7, whereas one of the 20 patients had positive ImmunoCAP results for Pru p 3. In 13 nPru p 7-sensitized patients, the causative foods were peaches (92.3%), apricots (61.5%), oranges (46.2%) and apples (30.8%). Ten patients (76.9%) had multiple causative fruits. Frequent symptoms included facial edema (92.3%) and laryngeal tightness (66.7%). In eight patients (61.5%), exercise or aspirin intake enhanced the allergic reaction onset as cofactors. The prevalence of GRP sensitization was high in Japanese fruit allergy patients except for PFAS patients. In conclusion, GRP-sensitized patients may have allergies to multiple fruits and may show peculiar characteristics such as facial swelling and cofactor dependence.


Contact glasses for use with high power lasers. Two new contact glasses for microsurgery at the iris, in the pupillary and the retropupillary space.
Two new contact glasses, one for irradiation of the iris and the other for irradiation of pathological structures within the pupillary and retropupillary regions are described. First order geometric considerations using the Young-Weierstrass imaging theorem indicate nearly aberration-free, stigmatic focussing, even for large numerical apertures. For surgical tasks utilizing high-power lasers, excellent focussing of strongly convergent ray-bundles which lead to small focus diameter and large diameters while passing through the pre-focal optical media are seen to be essential. Thus the efficiency of the laser-surgical treatment, its reliability, as well as security and harmlessness within the pre-focal media are increased.


Inhibitory effect of halocyamine, an antimicrobial substance from ascidian hemocytes, on the growth of fish viruses and marine bacteria.
Halocyamine A, an antimicrobial substance isolated from hemocytes of the solitary ascidian Halocynthia roretzi, inhibited in vitro the growth of fish RNA viruses (infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus). Pretreatment of RNA virus with halocyamine A reduced the infectivity of the virus toward host cells. The growth of marine bacteria, Achromobacter aquamarinus and Pseudomonas perfectomarinus, was also inhibited by halocyamine A but that of Alteromonas putrefaciens and Vibrio anguillarum was not. These results suggest that halocyamine may have a role in the defense mechanisms of H. roretzi against marine viruses and bacteria.


Docking and molecular dynamics studies of peripheral site ligand-oximes as reactivators of sarin-inhibited human acetylcholinesterase.
In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.


Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study.
Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1-2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04-3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1-4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997-0.999, p = 0.01). In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices.


Studies pertaining to language impairment in school-age autistic individuals underreport participant socio-demographics: A systematic review.
Although exclusion of racially and ethnically minoritized autistic individuals from research is a long-standing issue, we have yet to determine how exclusion impacts areas of autism research important for identifying language impairment. Diagnosis depends on the quality of the evidence (i.e. research) and is often the pathway to gaining access to services. As a first step, we examined how research studies related to language impairment in school-age autistic individuals report participant socio-demographics. We analyzed reports using age-referenced assessments in English (n = 60), which are commonly used by both practitioners and researchers to diagnose or identify language impairment. Findings showed only 28% of studies reported any information on race and ethnicity; in these studies, most (at least 77%) of the participants were white. In addition, only 56% of studies reported gender or sex and specified what they were reporting (gender, sex, or gender identity). Just 17% reported socio-economic status using multiple indicators. Altogether, findings indicate broad issues with underreporting and exclusion of racially and ethnically minoritized individuals, which might overlay with other aspects of identity including socio-economic status. It is impossible to determine the extent and precise nature of exclusion without intersectional reporting. To ensure that language in autism research is representative of the autistic population, future research must implement reporting guidelines and broaden inclusion of who participates in research studies.


Deep Learning Applied to Ligand-Based De Novo Drug Design.
In the latest years, the application of deep generative models to suggest virtual compounds is becoming a new and powerful tool in drug discovery projects. The idea behind this review is to offer an updated view on de novo design approaches based on artificial intelligent (AI) algorithms, with a particular focus on ligand-based methods. We start this review by reporting a brief overview of the most relevant de novo design approaches developed before the use of AI techniques. We then describe the nowadays most common neural network architectures employed in ligand-based de novo design, together with an up-to-date list of more than 100 deep generative models found in the literature (2017-2020). In order to show how deep generative approaches are applied into drug discovery context, we report all the now available studies in which generated compounds have been synthetized and their biological activity tested. Finally, we discuss what we envisage as beneficial future directions for further application of deep generative models in de novo drug design.


Quorum-based model learning on a blockchain hierarchical clinical research network using smart contracts.
Collaborative privacy-preserving modeling across several healthcare institutions allows for the construction of more generalizable predictive models while protecting patient privacy. We aim at addressing the site availability issue on a hierarchical network by designing an immutable/transparent/source-verifiable quorum mechanism. We developed an approach to combine a hierarchical learning algorithm, a novel Proof-of-Quorum (PoQ) consensus protocol, and a design of blockchain smart contracts. We constructed QuorumChain as an example and evaluated the scenarios of site-unavailability during the initialization and/or iteration phases of the modeling process on three healthcare/genomic datasets. When one or more sites would become unavailable, HierarchicalChain could not function, whereas QuorumChain improved predictive correctness significantly (the full Area Under the receiver operating characteristic Curve, or AUC, improved from 0.068 to 0.441, all with p-values < 0.001). By constructing a quorum to continue the modeling process, QuorumChain possesses the capability to tackle the situation of sites being unavailable. It inherits the capability of learning on network-of-networks, improves learning continuity, and provides data/software immutability, transparency, and provenance, which can be important in expediting clinical research.


Studies on stable isotopic composition of daily rainfall from Kozhikode, Kerala, India.
The stable isotopic compositions of all major daily rain fall samples (n = 113) collected from Kozhikode station in Kerala, India, for the year 2010 representing the pre-monsoon, southwest and northeast monsoon seasons are examined. The isotopic variations δ(18)O, δ(2)H and d-excess in daily rainfall ranged from δ(18)O: -4.4 to 2 ‰, δ(2)H: -25.3 to 13.8 ‰, and d-excess: -2.4 to 15.3 ‰; δ(18)O: -9.7 to -0.6 ‰, δ(2)H: -61.7 to 5.3 ‰, and d-excess 5.8 to 17.4 ‰; δ(18)O -11.3 to -1.4 ‰, δ(2)H: -75.3 to 0.9 ‰, and d-excess: 8.8 to 21.3 ‰ during the pre-, southwest and northeast monsoon periods, respectively. Thus, daily rainfall events during two monsoon periods had a distinct range of isotopic variations. The daily rain events within the two monsoon seasons also exhibited periodic variations. The isotopic composition of rain events during pre-monsoon and a few low-intensity events during the southwest monsoon period had imprints of secondary evaporation. This study analysing the stable isotopic characteristics of individual rain events in southern India, which is influenced by dual monsoon rainfall, will aid in a better understanding of its mechanism.


Assessment of Vestibulo-oculomotor Reflex in Ménière's Disease: Defining an Instrumental Profile.
To analyze and compare, in two groups of patients affected by definite Ménière's disease (MD) but treated differently, the Video Head Impulse Test findings especially by putting them in relationship with canal paresis, hearing loss, and duration of the disease. Retrospective chart review. Seventy patients affected by unilateral definite MD (16 in Group 1 and 54 in Group 2) observed between March 2014 and May 2015 in a tertiary referral center were retrospectively studied and then divided into two groups: Group 1 was previously treated with intratympanic gentamicin, whereas Group 2 underwent only a conservative therapy. Instrumental tests included audiometry, caloric test, and Video Head Impulse Test. All the findings were statistically analyzed; significance was set at p = 0.005. Diagnostic. If MD is treated conservatively the high-frequency vestibulo-oculomotor reflex gain determined with Video Head Impulse Test is normal; it is pathological if MD is treated with gentamicin. High-frequency vestibulo-oculomotor reflex gain showed a statistically significant reduction in Group 1; at the same time, it showed no correlation in both groups with hearing loss, duration of disease or canal paresis. High-frequency vestibulo-oculomotor reflex is naturally preserved even in late stage MD if the patient has been treated conservatively; the dissociation between Caloric Test and Video Head Impulse Test findings could be considered an instrumental hallmark of MD. Gentamicin significantly reduces high-frequency vestibulo-oculomotor reflex gain: this reduction can be taken into account when determining the effectiveness of an ablative treatment.


Radiomics signature for the prediction of progression-free survival and radiotherapeutic benefits in pediatric medulloblastoma.
To develop and validate a radiomics signature for progression-free survival (PFS) and radiotherapeutic benefits in pediatric medulloblastoma. We retrospectively enrolled 253 consecutive children with medulloblastoma from two hospitals. A total of 1294 radiomic features were extracted from the region of tumor on the T1-weighted and contrast-enhanced T1-weighted (CE-T1w) MRI. Radiomic feature selection and machine learning modelling were performed to build radiomics signature for the prediction of PFS on the training set. Moreover, the prognostic performance of the clinical parameters was investigated for PFS. The Concordance index (a value of 0.5 indicates no predictive discrimination, and a value of 1 indicates perfect predictive discrimination) was used to measure and compare the prognostic performance of these models. The radiomics signature for the prediction of the PFS yielded Concordance indices of 0.711, 0.707, and 0.717 on the training and held-out test sets 1 and 2, respectively. The radiomics nomogram integrating the radiomics signature, age, and metastasis performed better than the nomogram incorporating only clinicopathological factors (C-index, 0.723 vs. 0.665 and 0.722 vs. 0.677 on the held-out test sets 1 and 2, respectively), which was also validated by the good calibration and decision curve analysis. Further analysis demonstrated that patients with lower value of radiomics signature were associated with better clinical outcomes after postoperative radiotherapy (p < 0.001). The radiomics signature and nomogram performed well for the prediction of PFS and could stratify patients underwent postoperative radiotherapy into the high- and low-risk groups with significantly different clinical outcomes.


Synthesis of a novel class of nitrido Tc-99m radiopharmaceuticals with phosphino-thiol ligands showing transient heart uptake.
A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc(triple bond)N multiple bond and two bidentate phosphine-thiol ligands [R(2)P-(CH(2))(n)SH, n=2,3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands. When R=phenyl, heart activity was rapidly eliminated within 10-20 min. Instead, when R=tolyl, cyclohexyl, persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys.


Multiple inflammatory syndrome in children (MIS-C) has casuistically been reported in conjunction with retropharyngeal oedema. This case report details the diagnosis and treatment of MIS-C in a 13-year-old girl where the initial treatment was targeted against the retropharyngeal oedema. The aim is to highlight the atypical presentation of MIS-C.


Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.
Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures.


Disaster preparedness in Virginia Hospital Center-Arlington after Sept 11, 2001.
True disaster readiness and preparedness are not really measured until put to the test of a real disaster. The attacks of Sept 11, 2001, put 1 community hospital and its disaster plan to the ultimate test. The process the hospital used to review, evaluate, and change its former disaster plan and then implement a new plan on the basis of the response to Sept 11 terrorists attacks is described. Specific challenges faced by this community hospital, the importance of participation in a regional response effort, and how the hospital has readied itself in a new threat environment are addressed. Disasters affect hospitals of all sizes and geographic locations. Health care facilities need a strong framework with which to function independently, if only for a short time, until additional resources can be implemented.


Soil dehydrogenase, phosphomonoesterase and arginine deaminase activities in an insecticide treated groundnut (Arachis hypogaea L.) field.
Chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2 pyridyl phosphorothioate) 20 EC and Quinalphos (O,O-diethyl O-quinoxalin-2-yl phosphorothioate) 25 EC, were applied in groundnut (Arachis hypogaea L.) field as seed treatment at 25 ml/kg and soil treatment at 4 l/ha in 1998 and 1999. The residues of these insecticides were monitored during the entire crop season and their effect on the soil enzymes dehydrogenase, phosphomonoesterase and arginine deaminase were studied. Ninety nine percent of chlorpyrifos residues were dissipated within 60 days from seed treated soil and 98% dissipation was observed in soil treated field for the same days. Its half lives in seed treated soil were 8 days and 7 days and in soil treated field were 9.2 days in and 7.5 days in 1998 and 1999 respectively. Dissipation of quinalphos in comparison to chlorpyrifos was slow both in seed treated and soil treated field. Eighty seven percentage to 92% dissipation of quinalphos residues were observed from seed treated soil and 98% residues were dissipated from soil treated field within 75 days. Its half lives in seed treated soil were 20 days and 18 days and in soil treated field, its half lives were 13 days and 17 days 1998 and 1999 respectively. Inhibition in dehydrogenase activity followed by recovery was observed both in seed and soil treatments with chlorpyrifos. An inhibition of 17.2% was estimated after 60 days of seed treatment in comparison to control. Dehydrogenase activity was significantly reduced to 63% after 15 days of quinalphos seed treatment in comparison to control in 1998. Similar trends were observed in 1999. A significant inhibition in dehydrogenase activity was observed after soil treatment both in 1998 and 1999. Phosphomonoesterase activities were significantly inhibited upto 25.2% as compared to the control, on the 15th day of chlorpyrifos seed treatment in 1998 and similarly, after one day of treatment in 1999. Quinalphos inhibited the phosphomonoesterase activity till the end of the experimental period in the soil treated fields, whereas recovered within 30-60 days of treatment in the seed treated fields. Arginine deaminase activity was significantly stimulated within one day after chlorpyrifos seed and soil treatments in both years. The activity was almost threefold higher on the 30th and the 15th day of soil treatment in 1998 and 1999, respectively. A temporary inhibition of arginine deaminase activity was observed after quinalphos treatment. It was observed that in most of cases insecticides have temporary inhibitory effect on soil enzymes. However, inhibition was smaller in seed treated soil than in direct soil treatment.


Application of the Rietveld method to assess chromium(VI) speciation in chromite ore processing residue.
The Rietveld method allows the quantification of crystalline phases and amorphous material identified by X-ray powder diffraction (XRPD) and other diffraction methods. The method assists in determining the speciation of contaminants in solid matrices both qualitatively and quantitatively in a statistically defensible approach, as it does not focus on a microscale. Rietveld was applied to chromite ore processing residue (COPR), a cementitious waste containing hexavalent chromium. Calcium aluminum chromium oxide hydrates (CACs) were the crystalline phases identified by XRPD that bind Cr(6+) in COPR according to their chemical formula. Rietveld quantification, combined with mass balances on Cr(6+), showed that CACs may bind Cr(6+) in variable percentages, ranging from 25% to 85%. Analysis of duplicate samples showed that material variability is the predominant factor of uncertainty in evaluating the role of CACs in Cr(6+) speciation, provided that a consistent quantification strategy is pursued. The choice of strategy was performed on the basis of the pertinent literature, preliminary analyses of the equipment and the software settings, and mass balances. The correlation between the average CAC-bound Cr(6+) concentration and the total Cr(6+) for five samples (R(2)=0.94), extracted from different zones and soil borings, suggests that CACs are a primary sink for Cr(6+) in COPR.


Semen characteristics and sperm morphology of serow (Capricornis sumatraensis).
The serow (Capricornis sumatraensis) is a critically endangered species. The objectives of this study were to evaluate ejaculate quality in captive males, and to investigate and characterize sperm morphology. Semen was collected using electroejaculation. Mean (+/-S.D.) seminal characteristics were: semen volume 2.3+/-0.8 mL, pH 7.8+/-0.4, and osmolality 329.9+/-32.9mOsmol/kg; sperm concentration 515.8+/-263.1 x 10(6) cells/mL; wave motion score (1-5) 3.9+/-0.4; motile sperm 60.5+/-22%; viable sperm 68.3+/-9.4%; morphologically normal sperm 70.8+/-19.3%; and an opacity that was yellowish to milky-white. Sperm head length, width, degree of elongation, area, and perimeter were 6.0+/-0.6 microm, 4.3+/-0.3 microm, 71.7+/-8.6%, 19.8+/-2.5 microm(2), and 17.9+/-2.1 microm. Based on these measurements, we categorized sperm head morphometry as small, medium, or large. In addition, sperm morphology was examined by light and scanning electron microscopy; overall, morphologically normal and abnormal sperm were similar to those reported for other bovidae. In summary, this study provided baseline data regarding semen characteristics of C. sumatraensis, which should be of value in the preservation of this endangered species.


Efficacy of enteric-coated mycophenolate sodium in patients with active lupus nephritis.
The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. The mean age of the patients was 32.3 +/- 11.2 years and the average length of follow up was 25.9 +/- 8.9 months. The mean serum creatinine clearance was 93 +/- 30.1 mL/min per 1.73 m(2) and the mean proteinuria level was 4.5 +/- 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 +/- 9.7 months with an averaged starting dose of 1350 +/- 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 +/- 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis.


p53 in the cytoplasm: a question of overkill?
The tumor suppressor p53 regulates cellular responses to stress by serving in the nucleus to regulate transcription of genes involved in processes including cell cycle arrest, DNA repair, and apoptosis. Nevertheless, recent papers show that p53 may have a separate cytoplasmic role in directly regulating the Bax-dependent mitochondrial pathway to cell death.


Concentration-Dependent Structural Transition of the HIV-1 gp41 MPER Peptide into α-Helical Trimers.
The membrane proximal external region (MPER) of HIV-1 gp41 contains epitopes for at least four broadly neutralizing antibodies. Depending on solution conditions and construct design, different structures have been reported for this segment. We show that in aqueous solution the MPER fragment (gp160660-674 ) exists in a monomer-trimer equilibrium with an association constant in the micromolar range. Thermodynamic analysis reveals that the association is exothermic, more favorable in D2 O than H2 O, and increases with ionic strength, indicating hydrophobically driven intermolecular interactions. Circular dichroism, 13 Cα chemical shifts, NOE, and hydrogen exchange rates reveal that MPER undergoes a structural transition from predominately unfolded monomer at low concentrations to an α-helical trimer at high concentrations. This result has implications for antibody recognition of MPER prior to and during the process where gp41 switches from a pre-hairpin intermediate to its post-fusion 6-helical bundle state.


"But then i learned…": weight loss surgery patients negotiate surgery discourses.
This research explores commonplace discursive depictions of obesity surgery and individual patients' reactions to these depictions. Data come from a content analysis of weight loss surgery representations in periodical articles (n = 32) and open-ended surveys (n = 55) and interviews (n = 44) with surgery patients from 34 US states. This study reveals that mainstream periodicals frequently stigmatized patients as obesity surgery is cast as (1) medically risky, (2) extravagant and (3) an overly easy escape from obesity. Surgery is only portrayed as (4) acceptable when multiple other weight loss techniques had been tried unsuccessfully. In contrast, interview and survey data show individual patients are aware of, yet frequently refute, these surgical stigmas. Findings demonstrate the importance of weight loss surgery patients' personal experiences, interactions and education in shaping their responses to stigma. Patients view themselves as expert insiders who negotiate dominant discourses and, consequently, assert that surgery and surgery patients are ethical. Research results reveal the importance of perceived expert insider status and interpretive practice in managing obesity surgery stigma.


Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease.
To identify indicators of root caries among persons with newly diagnosed Alzheimer's disease (AD). Few studies have investigated dental caries in older adults with AD. Previously we found that persons with AD had significantly more root caries compared to persons with dementia other than AD. Participants were recruited from two university hospital clinics in Copenhagen, Denmark. A team of neurologists/geriatricians carried out the diagnostic screening. The study included an interview, oral examination and medical records. We evaluated potential indicators of root decay across subjects with 3+ decayed surfaces vs. <3 decayed surfaces. Variables associated with increased odds of root caries were age over 80 years, 2+ decayed coronal surfaces and 5+ filled root surfaces. Among the social variables, living with someone was associated with a nearly 70% reduction in the odds of having 3+ surfaces of untreated caries. Root caries is highly prevalent among individuals with new AD and there is still a strong need for active assessment of and attention to oral problems in persons with AD. Our findings document that recently diagnosed AD cases with multiple coronal caries lesions are at elevated risk of having more root caries. Also persons 81+ years and those with multiple root fillings are more likely to have numerous untreated root lesions.


[Bite mark analysis. Part 2. A selection of Dutch cases].
This contribution reflects the author's experiences with three selected bite mark analyses. One case concerns a bite mark found on mortal remains, one found on a living person and one found on food.