Augmentation of cellular immunity by kigamicin D.
Kigamicin D did not show any immunosuppressive activity in mixed lymphocyte culture reaction and mitogen induced lymphocyte blastogenesis in vitro and graft versus host reaction in vivo. Natural killer cell activity in spleen cells was not affected by oral administration of kigamicin D. Instead, delayed-type hypersensitivity response to sheep red blood cells was stimulated at a broad dosage level. It is concluded that kigamicin D increases cellular immunity to specific antigen.


The role of LTR retrotransposons in plant genetic engineering: how to control their transposition in the genome.
We briefly discuss that the similarity of LTR retrotransposons to retroviruses is a great opportunity for the development of a genetic engineering tool that exploits intragenic elements in the plant genome for plant genetic improvement. Long terminal repeat (LTR) retrotransposons are very similar to retroviruses but do not have the property of being infectious. While spreading between its host cells, a retrovirus inserts a DNA copy of its genome into the cells. The ability of retroviruses to cause infection with genome integration allows genes to be delivered to cells and tissues. Retrovirus vectors are, however, only specific to animals and insects, and, thus, are not relevant to plant genetic engineering. However, the similarity of LTR retrotransposons to retroviruses is an opportunity to explore the former as a tool for genetic engineering. Although recent long-read sequencing technologies have advanced the knowledge about transposable elements (TEs), the integration of TEs is still unable either to control them or to direct them to specific genomic locations. The use of existing intragenic elements to achieve the desired genome composition is better than using artificial constructs like vectors, but it is not yet clear how to control the process. Moreover, most LTR retrotransposons are inactive and unable to produce complete proteins. They are also highly mutable. In addition, it is impossible to find a full active copy of a LTR retrotransposon out of thousands of its own copies. Theoretically, if these elements were directly controlled and turned on or off using certain epigenetic mechanisms (inducing by stress or infection), LTR retrotransposons could be a great opportunity to develop a genetic engineering tool using intragenic elements in the plant genome. In this review, the recent developments in uncovering the nature of LTR retrotransposons and the possibility of using these intragenic elements as a tool for plant genetic engineering are briefly discussed.


Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine.
. Methyltransferases (Mtases) catalyze the transfer of methyl groups from S-adenosylmethionine (AdoMet) to a variety of small molecular and macromolecular substrates. These enzymes contain a characteristic alpha/beta structural fold. Four groups of DNA Mtases have been defined and representative structures have been determined for three groups. DpnM is a DNA Mtase that acts on adenine N6 in the sequence GATC; the enzyme represents group alpha DNA Mtases, for which no structures are known. . The structure of DpnM in complex with AdoMet was determined at 1.80 A resolution. The protein comprises a consensus Mtase fold with a helical cluster insert. DpnM binds AdoMet in a similar manner to most other Mtases and the enzyme contains a hollow that can accommodate DNA. The helical cluster supports a shelf within the hollow that may recognize the target sequence. Modeling studies indicate a potential site for binding the target adenine, everted from the DNA helix. Comparison of the DpnM structure and sequences of group alpha DNA Mtases indicates that the group is a genetically related family. Structural comparisons show DpnM to be most similar to a small-molecule Mtase and then to macromolecular Mtases, although several dehydrogenases show greater similarity than one DNA Mtase. . DpnM, and by extension the DpnM family or group alpha Mtases, contains the consensus fold and AdoMet-binding motifs found in most Mtases. Structural considerations suggest that macromolecular Mtases evolved from small-molecule Mtases, with different groups of DNA Mtases evolving independently. Mtases may have evolved from dehydrogenases. Comparison of these enzymes indicates that in protein evolution, the structural fold is most highly conserved, then function and lastly sequence.


Analysis of deaths between 2007 and 2012 of patients with cancer of the head and neck on a surgical ward at a regional centre and in an independent hospice.
Providing the best care for patients dying from cancer of the head and neck is crucial, and their complex, unpredictable needs, particularly at the end of life, mean that they are likely to die in institutional care. To evaluate the care given at the end of life we retrospectively reviewed the case notes of patients who died between 2007 and 2012 in a regional head and neck unit and a specialist palliative care unit (hospice). Deaths were categorised as sudden (rapid or unanticipated) or expected (gradual or anticipated). A total of 105 patients died, of whom 29 were excluded from analysis because records were missing. Of the remaining 76, 63 died in the head and neck unit and 13 in the hospice. Patients who died the hospice were younger (mean (SD) age 63.7 (11.0) years) than those who died in hospital (mean (SD) age 70.6 (11.9) years). Most had stage III or IV disease (head and neck unit 45/57, 79%, hospice 9/13, 69%). Death was sudden in 33 (43%) and expected in 43 (57%). Haemorrhage was the commonest cause of sudden death (n=13) and carcinomatosis (n=17) the commonest cause of expected death. Specialists in palliative care had been involved in the care of 13 patients who died suddenly (39%) and 34 whose deaths were expected (79%). The family was present at the time of death (or was aware of it) in 30 who died suddenly (91%) and in 40 (93%) whose deaths were expected. In patients with cancer of the head and neck death can be sudden because of unpredictable complications, and everyone should be aware of this.


A BioSpi model of lymphocyte-endothelial interactions in inflamed brain venules.
This paper presents a stochastic model of the lymphocyte recruitment in inflammed brain microvessels. The framework used is based on stochastic process algebras for mobile systems. The automatic tool used in the simulation is the BioSpi. We compare our approach with classical hydrodinamical specifications.


Predictors of the quality of life in Chinese breast cancer survivors.
Little is known about the importance of various factors which impair the quality of life (QOL) in survivors of breast cancer 1 year after diagnosis and over 1 year after diagnosis in China. Hence, the goal of this article is to quantitatively evaluate the factors which play an active role in impairing QOL 1 year after diagnosis and over 1 year after diagnosing survivors. A population-based cross-sectional study was conducted at 34 Cancer Recovery Clubs across China from May 2014 to January 2015. The simplified Chinese version of the Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) and the Breast Cancer-specific module QLQ-23 were used to measure QOL in 10794 Chinese women with breast cancer (1 year after diagnosis: 1029, over 1 year after diagnosis: 9765). Forward stepwise multivariable regression analysis was used to identify the most predictive factors for limitations on QOL. Partial R 2 values were calculated to appraise the independent proportion of explained variance within QOL by each factor included in the model. The participants had higher scores of role functioning, sexual function, sexual enjoyment, and financial difficulties. The uppermost predictors of functional status and QOL were financial difficulties and fatigue for the 1 year after diagnosis, respectively, and fatigue, financial difficulties, and systemic side effects for the long-term survivors. These symptoms explained approximately 28-53% of the variability within the function scores and QOL expect for sexual enjoyment and sexual functioning. Although sociodemographic and clinical factors had a relative importance to sexual function and sexual enjoyment, they were even smaller and had less of an impact on other dimensions. People who were more active and had an optimistic attitude towards life had relatively higher function scores. For the breast cancer patients 1 year after diagnosis, reducing the burden of fatigue might be a more preferable way to improve their functional status and QOL. Nevertheless, focusing on fatigue symptoms and systemic therapy side effects synchronously may present an especially worthwhile endeavor to enhance the long-term survivors' functional status and QOL.


Analysis of tumor vessel supply in Lewis lung carcinoma in mice by fluorescent microsphere distribution and imaging with micro- and flat-panel computed tomography.
In lung carcinomas the blood supply varies depending on tumor type and stage and can develop from pulmonary or bronchial circulation, or both. To examine this in vivo, primary bronchogenic Lewis lung carcinoma cells were intratracheally instilled in C57BL/6 mice. Within 7 days, histological examinations showed progressive tumor growth at the peripheral parenchymal region. The relative contribution of tumor blood supply via the pulmonary and systemic arteries was studied in detail using fluorescent microspheres (10 microm). When compared to healthy lung parenchyma (13:1), Lewis lung carcinoma tumor tissue (52:1) showed a fourfold increase in pulmonary to systemic microspheres, indicating that the pulmonary arteries are the predominant tumor-feeding vessels. After filling the vessels with a vascular cast, the microanatomy of vessels being derived from the pulmonary artery was visualized with micro computed tomography. Flat-panel volumetric computed tomography provided longitudinal visualization of tissue bridges between the growing tumor and the pulmonary vasculature. In this model of peripheral parenchymal malignancy, new imaging techniques allowed effective visualization of lung tumor growth and vascularization in living mice, demonstrating a pulmonary blood supply for lung tumors.


Trade-offs in the transition to a blue economy - Mapping social acceptance of aquaculture expansion in Norway.
Aquaculture is currently the fastest growing food industry globally, and proposed expansion plans include substantial increases in production over the next decades. While this will improve global food security, contribute to the blue economy and create jobs locally, the potential negative impacts on the marine environment could be massive. The existing literature suggests that further research needs to be conducted into the dynamic nature of the social-ecological systems which host aquaculture. This paper presents the results of a choice experiment survey of Norwegian households' trade-offs between salmon production and job creation, and the detrimental impacts on the marine environment. Most respondents were at the outset neutral or supportive of plans for a substantial increase in aquaculture production. However, when informed about potential environmental impacts in terms of marine plastics and salmon lice affecting wild salmon stocks, and asked to trade these off against the positive effects, the majority opposed the plans and expressed a positive willingness-to-pay to avoid the planned expansion. Applying a hybrid mixed multinomial logit model we find that income, education and to some extent age, along with environmental attitudes, explain most of the variation in people's preferences. Support for large aquaculture expansion is higher among people who consume farmed salmon frequently and those living in areas with a high density of aquaculture farms. Hence, we do not find the so-called "not in my backyard" (NIMBY) effect. These results, which arguably contrast with previous studies of environmental impacts from aquaculture, can be useful for public planners globally as they consider expanding the blue economy.


The association between childhood relocations and subsequent risk of suicide attempt, psychiatric problems, and low academic achievement.
Given the frequency with which families change residences, the effects of childhood relocations have gained increasing research attention. Many researchers have demonstrated that childhood relocations are associated with a variety of adverse outcomes. However, drawing strong causal claims remains problematic due to uncontrolled confounding factors. We utilized longitudinal, population-based Swedish registers to generate a nationally representative sample of offspring born 1983-1997 (n = 1 510 463). Using Cox regression and logistic regression, we examined the risk for numerous adverse outcomes after childhood relocation while controlling for measured covariates. To account for unmeasured genetic and environmental confounds, we also compared differentially exposed cousins and siblings. In the cohort baseline model, each annual relocation was associated with risk for the adverse outcomes, including suicide attempt [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.19-1.20]. However, when accounting for offspring and parental covariates (HR 1.08, 95% CI 1.07-1.09), as well as genetic and environmental confounds shared by cousins (HR 1.07, 95% CI 1.05-1.09) and siblings (HR 1.00, 95% CI 0.97-1.04), the risk for suicide attempt attenuated. We found a commensurate pattern of results for severe mental illness, substance abuse, criminal convictions, and low academic achievement. Previous research may have overemphasized the independent association between relocations and later adverse outcomes. The results suggest that the association between childhood relocations and suicide attempt, psychiatric problems, and low academic achievement is partially explained by genetic and environmental confounds correlated with relocations. This study demonstrates the importance of using family-based, quasi-experimental designs to test plausible alternate hypotheses when examining causality.


A negative feedback loop of H19/miR-675/EGR1 is involved in diabetic nephropathy by downregulating the expression of the vitamin D receptor.
We aimed to explore the regulatory relationship among the long noncoding RNA H19, micorRNA-675 (miR-675), the vitamin D (VD) receptor (VDR), and the early growth response protein 1 (EGR1) in the pathogenesis of diabetic nephropathy (DN) among patients with diabetes mellitus (DM). Expression levels of H19, miR-675, VDR, and EGR in patients or CIHP-1/HEK 293 cells were measured via quantitative reverse-transcription polymerase chain reaction and western blot analysis. Computational analysis and luciferase assays were performed to determine EGR1 as a target gene of miR-675. The relative expression of miR-675 was higher in the presence of H19, whereas the expression of both VDR and EGR1 messenger RNA was decreased in the presence of H19 or miR-675. However, relative expression of H19 and miR-675 was increased, whereas VDR expression was suppressed upon the treatment of 1,25-dihydroxyvitamin D3 or EGR1. VDR was identified as a target gene of miR-675. The H19 promoter and EGR1 increased the luciferase activity of cells transfected with wild-type VDR. Compared with DM patients free of DN, the levels of H19 and miR-675 were increased in the DN(+) group, whereas the levels of VDR and EGR1 were decreased. In summary, the above results indicate the presence of a negative feedback loop in the pathological mechanism of DN, where H19 downregulates the expression of VDR by upregulating the expression of miR-675, whereas reduced VDR expression subsequently reduced the expression of EGR1. Moreover, reduced EGR1 expression inhibits H19 expression, thus forming a negative feedback loop required to maintain the homeostasis of VDR and to reduce the incidence of DN.


Adherence with lipid screening guidelines in standard- and high-risk children and adolescents.
Because atherosclerosis begins in childhood, universal lipid screening is recommended with special attention to conditions predisposing to early atherosclerosis. Data about real-world penetration of these guidelines is not available. Retrospective cohort study using MarketScan® commercial and Medicaid insurance claims databases, a geographically representative sample of U.S. children. Subjects who passed through the 9- to 11-year window and had continuous insurance coverage between 1/1/2013 and 12/31/2016 were studied. Multivariable models were calculated, evaluating the association between other patient factors and the likelihood of screening. The primary hypothesis was that screening rates would be low, but that high-risk conditions would be associated with a higher likelihood of screening. In total, 572,522 children (51% male, 33% black, 11% Hispanic, 51% Medicaid) were studied. The prevalence of high-risk conditions was 2.2%. In unadjusted and adjusted analyses, these subjects were more likely to be screened than standard-risk subjects (47% vs. 20%, OR: 3.7, 95% CI 3.5-3.8, P < .001). Within this group, the diagnosis-specific likelihood of screening varied (26-69%). Endocrinopathies (OR 5.4, 95% CI 5.2-5.7), solid organ transplants (OR 5.0, 95% CI 3.8-6.6), and metabolic disease (OR 3.9, 95% CI 3.1-5.0, all P < .001) were associated with the highest likelihood of undergoing screening. Despite national recommendations, lipid screening was performed in a minority of children. Though subjects with high-risk conditions had a higher likelihood of screening, rates remained low. This study highlights the need for research and advocacy regarding obstacles to lipid screening of children in the United States.


Fungal fidelity: nuclear divorce from a dikaryon by mating or monokaryon regeneration.
Basidiomycete fungi perform fertilizations by incorporation of nuclei into a monokaryotic mycelium to establish a dikaryon. The dikaryon cannot incorporate another type of nucleus, but can still act as a nucleus donor in a dikaryon-monokaryon (di-mon) mating, known as the Buller phenomenon. Previously, it has been observed that: (1) in a particular di-mon mating, one of the nuclear types of the dikaryon generally performs better as a donor than the other, and (2) when nuclei from a dikaryon are separated to form monokaryons again (dedikaryotisation), recovery of monokaryons of the two nuclear types is usually unequal. In this study, we investigated if these two observations of asymmetry are functionally related. We tested this hypothesis by performing both di-mon matings and dedikaryotisation of dikaryons derived from five different monokaryons. When a single mechanism controls both processes, the nucleus better at fertilizing a monokaryon in a Buller pairing should also be recovered upon dedikaryotisation with a higher frequency. The results showed a hierarchical structure for recovery among nuclei in dedikaryotisation, but this hierarchy did not correspond to the fertilization success during di-mon mating. These findings thus show that the mechanism causing asymmetric regeneration of nuclei, is most likely not the same as the mechanism responsible for increased chance of fertilization in di-mon matings. We discuss the complexity of the interactions that occur during di-mon matings with regards to the mating type loci.


Immunohistochemical localization of oestrogen receptors and progesterone receptors in the human ovary throughout the menstrual cycle.
Immunohistochemistry was used to determine the distribution of oestrogen receptors (ER) and progesterone receptors (PR) in the human ovary during folliculogenesis. Primordial and preantral follicles did not contain ER or PR. The granulosa cells of antral follicles had ER, but negligible PR, before the LH surge. In contrast, at the time of LH surge, these cells of the dominant follicle contained PR, but not ER. On the other hand, granulosa cells of the non-dominant follicles had ER, but not PR. After ovulation, the PR persisted in the luteinized granulosa cells and in the corpus luteum during early pregnancy. The theca interna and surrounding stromal cells were ER-negative and PR-positive throughout the menstrual cycle. Thus, the results show that ER and PR are not expressed simultaneously in the granulosa cells, the thecal cells, or the stromal cells during folliculogenesis. Mechanisms controlling the expression of steroid receptors during the normal menstrual cycle and in early pregnancy are discussed.


Synthesis of disubstituted cucurbit[6]uril and its rotaxane derivative.
Synthesis of diphenyl cucurbit[6]uril (CB[6]) has been achieved via co-oligomerization of diphenyl glycoluril and unsubstituted glycoluril. The unsymmetrically substituted CB[6], Ph(2)CB[6], was further converted to a rotaxane incorporating bis(dinitrophenyl)spermine. [reaction: see text]


Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.
Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the compound in humans than in rats. PBPK simulations of verapamil identified gut wall metabolism, well established in the literature, and showed large interspecies differences with respect to both gut wall metabolism and drug-induced delays in gastric emptying. Mechanistic insights provided by PBPK simulations can be very valuable in answering vital questions in drug discovery and development. However, such applications of PBPK models are limited by the lack of accurate inputs for clearance and distribution. This article demonstrates a successful application of PBPK simulations to identify and quantify intestinal loss of two model compounds in rats and humans. The limitation of inaccurate inputs for the clearance and distribution parameters was overcome by optimizing these parameters through fitting intravenous profiles. The study also demonstrated that the large interspecies differences associated with gut wall metabolism and gastric emptying, evident for the compounds studied, make animal model extrapolations to humans unreliable. It is therefore important to do PBPK simulations of human pharmacokinetic profiles to understand the relevance of intestinal loss of a compound in humans.


Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma.
Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment. Although nanotechnology is widely applied in cancer therapy, poor targeting and inadequate efficiency hinder its development. In this study, we prepared alendronate (ALD)/K7M2 cell membranes-coated hollow manganese dioxide (HMnO2) nanoparticles as a nanocarrier to load Ginsenoside Rh2 (Rh2) for Magnetic Resonance imaging (MRI)-guided immuno-chemodynamic combination osteosarcoma therapy. Subsequently, the ALD and K7M2 cell membranes were successively modified on the surface of HMnO2 and loaded with Rh2. The tumor microenvironment (TME)-activated Rh2@HMnO2-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities, excellent GSH-sensitive drug release profile and MRI capability, and attractive immuno-chemodynamic combined therapeutic efficiency. The Rh2@HMnO2-AM nanoparticles can effectively trigger immunogenic cell death (ICD), activate CD4+/CD8+ T cells in vivo, and upregulate BAX, BCL-2 and Caspase-3 in cellular level. Further results revealed that Rh2@HMnO2-AM enhanced the secretion of IL-6, IFN-γ and TNF-α in serum and inhibited the generation of FOXP3+ T cells (Tregs) in tumors. Moreover, the Rh2@HMnO2-AM treatment significant restricted tumor growth in-situ tumor-bearing mice. Therefore, Rh2@HMnO2-AM may serve as an effective and bio-friendly nanoparticle platform combined with immunotherapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.


Cell wall formation pathways are differentially regulated in sugarcane contrasting genotypes associated with endophytic diazotrophic bacteria.
Differences in cell wall components between two BNF-contrasting sugarcane genotypes might result from genetic variations particular to the genotype and from the efficiency in diazotrophic bacteria association. Sugarcane is a plant of the grass family (Poaceae) that is highly cultivated in Brazil, as an important energy resource. Commercial sugarcane genotypes may be successfully associated with beneficial endophytic nitrogen-fixing bacteria, which can influence several plant metabolic pathways, such as cell division and growth, synthesis of hormones, and defense compounds. In this study, we investigated how diazotrophic bacteria associated with sugarcane plants could be involved in the regulation of cell wall formation pathways. A molecular and structural characterization of the cell wall was compared between two genotypes of sugarcane with contrasting rates of Biological Nitrogen Fixation (BNF): SP70-1143 (high BNF) and Chunee (low BNF). Differentially expressed transcripts were identified in transcriptomes generated from SP70-1143 and Chunee. Expression profiles of cellulose and lignin genes, which were more expressed in SP70-1134, and callose genes, which were more expressed in Chunee, were validated by RT-qPCR and microscopic analysis of cell wall components in tissue sections. A similar expression profile in both BNF-contrasting genotypes was observed in naturally colonized plants and in plants inoculated with G. diazotrophicus. Cell walls of the high BNF genotype have a greater cellulose content, which might contribute to increase biomass. In parallel, callose was concentrated in the vascular tissues of the low BNF genotype and could possibly represent a barrier for an efficient bacterial colonization and dissemination in sugarcane tissues. Our data show a correlation between the gene profiles identified in the BNF-contrasting genotypes and a successful association with endophytic diazotrophic bacteria.


A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer.
Ovarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598-4 cell line and how its genes are associated with ovarian cancer prognosis. We sequenced and annotated the eccDNA by Circle_seq of the OV cell line UACC-1598-4. To acquire the amplified genes of OV on eccDNA, the annotated eccDNA genes were intersected with the overexpression genes of OV in TCGA. Univariate Cox regression was used to find the genes on eccDNA that were linked to OV prognosis. The least absolute shrinkage and selection operator (LASSO) and cox regression models were used to create the OV prognostic model, as well as the receiver operating characteristic curve (ROC) curve and nomogram of the prediction model. By applying the median value of the risk score, the samples were separated into high-risk and low-risk groups, and the differences in immune infiltration between the two groups were examined using ssGSEA. EccDNA in UACC-1598-4 has a length of 0-2000 bp, and some of them include the whole genes or gene fragments. These eccDNA originated from various parts of chromosomes, especially enriched in repeatmasker, introns, and coding regions. They were annotated with 2188 genes by Circle_seq. Notably, the TCGA database revealed that a total of 198 of these eccDNA genes were overexpressed in OV (p < 0.05). They were mostly enriched in pathways associated with cell adhesion, ECM receptors, and actin cytoskeleton. Univariate Cox analysis showed 13 genes associated with OV prognosis. LASSO and Cox regression analysis were used to create a risk model based on remained 9 genes. In both the training (TCGA database) and validation (International Cancer Genome Consortium, ICGC) cohorts, a 9-gene signature could successfully discriminate high-risk individuals (all p < 0.01). Immune infiltration differed significantly between the high-risk and low-risk groups. The model's area under the ROC curve was 0.67, and a nomograph was created to assist clinician. EccDNA is found in UACC-1598-4, and part of its genes linked to OV prognosis. Patients with OV may be efficiently evaluated using a prognostic model based on eccDNA genes, including SLC7A1, NTN1, ADORA1, PADI2, SULT2B1, LINC00665, CILP2, EFNA5, TOMM.


Role of the radiologist in the diagnosis and management of the two forms of hepatic echinococcosis.
Echinococcosis is a parasitic disease caused by two zoonotic tapeworms (cestodes) of the Echinocococcus genus. It can be classified as either alveolar or cystic echinococcosis. Although the two forms differ significantly in terms of imaging findings, they share similarities in terms of management and treatment. In parallel to medical treatment with albendazole (ABZ), and surgery, historically used in these diseases, various imaging-guided interventional procedures have recently emerged (drainage, stenting, or Puncture, aspiration, injection, and reaspiration (PAIR)). These options open up a new range of therapeutic options. As in oncology, multidisciplinary consultation meetings now play a major role in adapted management and patient care in hepatic echinococcosis. Consequently, diagnostic imaging and interventional expertise have brought radiologists to the fore as important members of these multidisciplinary team. The radiologist will need to evaluate parasite activity in both forms of the disease, to guide the choice of the appropriate therapy from among medical treatment, interventional radiology procedures and/or surgical treatment. Knowledge of the specific complications of the two forms of echinococcosis will also help radiologists to discuss the appropriate treatment and management. The aim of this review is to describe the core knowledge that what a radiologist should possess to actively participate in multidisciplinary meetings about hepatic echinococcosis. We discuss the role of imaging, from diagnosis to treatment, in alveolar (AE) and cystic echinococcosis (CE), respectively.


Reconstruction and analysis of 137Cs fallout deposition patterns in the Marshall Islands.
Estimates of 137Cs deposition caused by fallout originating from nuclear weapons testing in the Marshall Islands have been estimated for several locations in the Marshall Islands. These retrospective estimates are based primarily on historical exposure rate and gummed film measurements. The methods used to reconstruct these deposition estimates are similar to those used in the National Cancer Institute study for reconstructing 131I deposition from the Nevada Test Site. Reconstructed cumulative deposition estimates are validated against contemporary measurements of 137Cs concentration in soil with account taken for estimated global fallout contributions. These validations show that the overall geometric bias in predicted-to-observed (P:O) ratios is 1.0 (indicating excellent agreement). The 5th to 95th percentile range of this distribution is 0.35-2.95. The P:O ratios for estimates using historical gummed film measurements tend to slightly overpredict more than estimates using exposure rate measurements. The deposition estimate methods, supported by the agreement between estimates and measurements, suggest that these methods can be used with confidence for other weapons testing fallout radionuclides.


Neuroprotection produced by the NAALADase inhibitor 2-PMPA in rat cerebellar neurons.
The present study examined the neuroprotective actions of the N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) in four in vitro models of neurotoxicity. Using neuron-enriched primary cultures derived from rat embryo (E15) cerebellum, 2-PMPA afforded 100% neuroprotection from injuries induced by hypoxia (EC(50)=8.4 microM). In contrast, against glutamate or N-methyl-D-aspartate (NMDA) injury, 2-PMPA was less potent and its efficacy limited to a maximum of 46% and 16%, respectively. 2-PMPA was not effective against veratridine-induced injury. Also, the less potent analog of 2-PMPA, 2-[phosphonomethyl]succinic acid (2-PMSA), was ineffective. Unlike 2-PMPA, the endogenous NAALADase substrate and mGlu(3) receptor agonist N-acetyl-aspartyl-glutamate (NAAG) was neuroprotective against all four injury mechanisms and compared to 2-PMPA, exhibited a different "phosphate effect" on neuroprotection. These results confirm the superior efficacy of 2-PMPA to protect against injury caused by cellular anoxia, and are discussed relative to upstream modulation of hyperglutamatergic activity vs. downstream modulation of metabotropic receptors as possible targets for ischemia/stroke therapy.


A validation study of the Stoyanova et al. method (2017) for age-at-death estimation quantifying the 3D pubic symphyseal surface of adult males of European populations.
The age-at-death estimation thresholds have recently been shifted towards a more objective assessment of the aging process. Such a non-subjective approach offers quantitative methods of age estimation; for instance, the method relating to the surfaces of pubic symphyses of males published by Stoyanova et al. (J Forensic Sci 62:1434-1444, 2017). A validation study was conducted to test the method performance in European samples. The sample consisted of 96 meshes of pubic symphyses of male individuals (known sex and age) that came from four different samples (two Portuguese collections, one Swiss, and one Crete). Stoyanova's method based on five regression models (three univariate and two multivariate models) performed worse in our sample, but only when the whole sample (without age limitation) was included. A sample limited to individuals under 40 years of age achieved better results in our study. The best results were reached through the thin plate spline algorithm (TPS/BE) with a root mean square error of 5.93 years and inaccuracy of 4.47 years. Generally, the multivariate regression models did not contribute to better age estimation. In our sample in all age categories, age was systematically underestimated. The quantitative method tested in this study works best for individuals under 40 years of age and provides a suitable basis for further research.


Effects of UGT1A4 genetic polymorphisms on serum lamotrigine concentrations in Chinese children with epilepsy.
Lamotrigine (LTG) is widely used in the treatment of children with epilepsy. Genetic polymorphisms in genes encoding drug-metabolizing enzymes may be an important source of interindividual variability in LTG metabolism. The aim of this study was to evaluate the effects of genetic polymorphisms of uridine diphosphate glucuronosyltransferase (UGT) 1A4 (UGT1A4) gene on LTG serum concentrations in children with epilepsy. The UGT1A4 142T > G in the coding regions and -219C > T/-163G > A in the 5'-upstream regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing in 148 patients treated with polytherapy with LTG and valproic acid (VPA). Our data showed that patients carrying the variant UGT1A4 -219C > T/-163G > A genotypes or alleles had significantly higher adjusted LTG concentrations than those carrying the wild-type genotypes or alleles. However, the significant association was abrogated after adjusted by age, body weight, and adjusted VPA concentration. No associations were detected between the UGT1A4 142T > G genotypes or alleles and adjusted LTG concentrations. Taken together, these results suggest that the -219C > T/-163G > A mutations in the 5'-upstream regions of the UGT1A4 gene affect LTG pharmacokinetics, with which is potentially interfered by age, body weight, and concomitant VPA administration.


Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.
The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses.


Decoration of titanium dioxide nanotubes with silver nanoparticles using the photochemical deposition method and their application as an electrocatalyst to determine tinidazole.
In this study, titanium nanotube electrodes were decorated with silver nanoparticles (AgNPs/TiO2NTs) and used as an electrocatalyst for the reduction of tinidazole. AgNPs/TiO2NTs are constructed by anodization of titanium sheet metal and photochemical deposition of AgNPs on TiO2NTs. The structural and elemental analysis characteristics of the AgNPs/TiO2NT electrode have been studied by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) methods. Based on the cyclic voltammetric data, it has been confirmed that the AgNPs/TiO2NT electrode has good electrocatalytic activity to reduce tinidazole. Two liner concentration ranges of 0.2-55.0 μM and 55.0-111.2 μM were obtained by amperometric method. A detection limit of 60.9 nM was obtained for measuring tinidazole at the AgNPs/TiO2NT electrode surface. In addition, the designed sensor has been successfully used for quantitative measurement of tinidazole in pharmaceutical and human urine samples.


Early and late acute lung injury and their association with distal organ damage in murine malaria.
Severe malaria is characterised by cerebral oedema, acute lung injury (ALI) and multiple organ dysfunctions, however, the mechanisms of lung and distal organ damage need to be better clarified. Ninety-six C57BL/6 mice were injected intraperitoneally with 5×10(6)Plasmodium berghei ANKA-infected erythrocytes or saline. At day 1, Plasmodium berghei infected mice presented greater number of areas with alveolar collapse, neutrophil infiltration and interstitial oedema associated with lung mechanics impairment, which was more severe at day 1 than day 5. Lung tumour necrosis factor-α and chemokine (C-X-C motif) ligand 1 levels were higher at day 5 compared to day 1. Lung damage occurred in parallel with distal organ injury at day 1; nevertheless, lung inflammation and the presence of malarial pigment in distal organs were more evident at day 5. In conclusion, ALI develops prior to the onset of cerebral malaria symptoms. Later during the course of infection, the established systemic inflammatory response increases distal organ damage.


Unique genetic profile of hereditary hemochromatosis in Russians: high frequency of C282Y mutation in population, but not in patients.
Hereditary hemochromatosis (HH) is a common cause of primary iron overload induced by genetic impairment of iron metabolism. More than 80% of HH patients in populations of European origin are homozygotes for a single mutation C282Y, or compound heterozygotes for C282Y and H63D mutations in the HFE gene. However, in the majority of Asian, African, Australasian, and Amerindian populations, frequencies of C282Y are close to zero. Data on the prevalence of HFE mutations in Russian population and in Russian patients with HH are very limited. In this work, we determined frequencies of C282Y and H63D in ethnical Russians living in the Central European region of Russia. Furthermore, we tested whether homozygocity for C282Y is the major cause of HH in Russians. We found that, in the Russian population, the frequency of C282Y mutation in the HFE gene is relatively high and corresponds to mean European levels. However, in contrast to the majority of European populations, homozygocity for C282Y is found only in a small proportion (5%) of patients with biochemical and clinical signs of HH. These data suggest that either the penetrance of C282Y in Russia is lower than in Western countries, or that a more frequent non-HFE dependent mechanism of primary iron overload dominates in Russian population.


Racial disparities in catheter related urinary tract infections among elderly trauma patients in the US.
Catheter associated urinary tract infections (CAUTIs) have become a focus for reducing healthcare costs. Reimbursement may be reduced to hospitals with higher rates. The implementation of bundles or other efforts to reduce infection numbers may not be as robust at hospitals caring for more diverse patient populations. This may lead to a disparity in hospital-associated infections rates that may lead to lower reimbursement and a downward spiral of quality of care and racial disparities. We analyzed patients in the National Trauma Data Bank from 2016 to 2017. The final analysis included patients 65 years or older with one or more day of mechanical ventilation. This was the population had the highest rate of CAUTI. We compared white patients to non-whites using students t test, Mann Whitney U test, or chi-square as appropriate. Logistic regression with odds ratios (ORs) and 95% confidence intervals (CI) was computed to identify risk factors for of CAUTI. Risk factors for developing a CAUTI were race (OR 1.44, 95% confidence interval (95%CI) 1.23-1.71), injury severity score (OR 1.10 per increase of one, 95% CI 1.01-1.02), care at a teaching hospital (OR 1.17, 95%CI 1.02-1.35), private insurance (OR 1.28, 95%CI 1.09-1.51), hypertension (OR 1.18, 95%CI 1.02-1.37), female gender (OR 1.54, 95%CI 1.33-1.77). Non-white patients received care at teaching hospitals more often and had a higher rate of government insurance or no insurance. The Center for Medicare and Medicaid Services (CMS) has put in place a reimbursement modification 87 plan based on the rates of hospital-associated infections including CAUTIs. We have demonstrated non-white 88 patients have higher odds for developing a CAUTI. CMS may potentially worsen the racial disparity by further cutting reimbursement to hospitals who care for higher proportions of non-whites.


Novel Brain-Tumor-Inhibiting Copper(II) Compound Based on a Human Serum Albumin (HSA)-Cell Penetrating Peptide Conjugate.
It is a great challenge to design drugs that penetrate the blood-brain barrier to inhibit brain tumor growth by acting against multiple targets and also improve their delivery efficacy and targeting ability to cancer cells. To overcome the above problems, we designed a multitarget metal agent for treating brain tumors based on an human serum albumin (HSA)-cell penetrating peptide conjugate. Thus, we rationally screened copper (Cu) and 2-acetyl-3-ethylpyrazine thiosemicarbazones to synthesize six compounds, and we investigated their structure-activity relationships and confirmed multiple mechanisms for brain glioma cells. The HSA-6b complex structure indicated that 6b binds to the IIA subdomain of HSA and His242 replaces the Br ligand in 6b in coordination with Cu2+. In vivo data suggested that both 6b and the HSA-6b-peptide conjugate penetrate the blood-brain barrier and inhibit brain tumor growth with few side effects. Furthermore, the HSA-peptide conjugate also improved the delivery efficacy and targeting ability of 6b in vivo.


Region-specific effects of hypothyroidism on the relative expression of thyroid hormone receptors in adult rat brain.
The aim of this study was to determine whether changes in the circulating thyroid hormone (TH) and brain synaptosomal TH content affected the relative levels of mRNA encoding different thyroid hormone receptor (TR) isoforms in adult rat brain. Northern analysis of polyA+RNA from cerebral cortex, hippocampus and cerebellum of control and hypothyroid adult rats was performed in order to determine the relative expression of all TR isoforms. Circulating and synaptosomal TH concentrations were determined by radioimmunoassay. Region-specific quantitative differences in the expression pattern of all TR isoforms in euthyroid animals and hypothyroid animals were recorded. In hypothyroidism, the levels of TRalpha2 mRNA (non-T3-binding isoform) were decreased in all brain regions examined. In contrast the relative expression of TRalpha1 was increased in cerebral cortex and hippocampus, whereas in cerebellum remained unaffected. The TRbeta1 relative expression in cerebral cortex and hippocampus of hypothyroid animals was not affected, whereas this TR isoform was not detectable in cerebellum. The TR isoform mRNA levels returned to control values following T4 intraperitoneal administration to the hypothyroid rats. The obtained results show that in vivo depletion of TH regulates TR gene expression in adult rat brain in a region-specific manner.


Application of simple sequence repeat (SSR) markers for molecular diversity and heterozygosity analysis in maize inbred lines.
There is an important role of understanding the genetic diversity among and within inbred lines at the molecular level for maize improvement in different breeding programs. The present study was devoted to estimate the level of genetic diversity among the inbred lines of maize using the simple sequence repeat analysis (SSR). The application of six different SSR markers successfully provided the information on similarity or diversity as well as the heterozygosity of the allelic loci for all the eight inbred line of maize.


The specialized competency framework for community pharmacists (SCF-CP) in Lebanon: validation and evaluation of the revised version.
In the absence of similar studies in Lebanon, this study aimed at upgrading and validating the Lebanese specialized competencies framework for community pharmacists (SCF-CP) as a tool to transform community practice and support the professional development and career progression of community pharmacists. Content validity was assessed and improved through a team of experts. After a thorough literature review and utilizing the Delphi technique, six domains were defined in the framework, with their respective competencies and behaviors. A cross-sectional study was then carried out from March to October 2022 using an online questionnaire created on Google Forms. The snowball technique was applied to reach community pharmacists across all the Lebanese governorates. The final sample included 512 community pharmacists. The construct validity of the framework was confirmed by factor analysis. The Kaiser-Meyer-Olkin measures of sampling adequacy were satisfactory for all models ranging from 0.500 to 0.956 with a significant Bartlett's test of sphericity (P < 0.001). The internal consistency of all competency domains was confirmed by Cronbach's alpha, with values ranging from 0.803 to 0.953. All competencies were significantly correlated with their respective domains (P < 0.001), and all domains were significantly correlated with each other and with the framework (P < 0.001). The participants declared being competent in all domains relating to fundamental skills, safe and rational use of medicines, pharmacy management, professional skills, public health fundamentals, and emergency preparedness and response, with some exceptions, such as compounding, management, and emergency preparedness. A higher declared competency level was associated with having more experience and receiving more than 50 patients per day. Our findings could demonstrate that the Lebanese specialized competency framework is a valid and reliable tool. This framework could help assess the minimum competencies that community pharmacists should possess or acquire and direct initial and continuing education for better practice. Hence, it could be adopted by the authorities and implemented in the Lebanese community pharmacy setting.


Predictive modeling, integrated DM emerge as popular strategies.
The traditional managed care strategies of capitation and selective provider contracting are losing their punch, as members have demanded broader networks and providers have pushed demands for fee-for-service payment. Health plans looking to regain an advantage can capitalize on two emerging disease management strategies--both of which rely on analyzing member data.


New vaccination strategies are required for effective control of winter ulcer disease caused by emerging variant strains of Moritella viscosa in Atlantic salmon.
Moritella viscosa is one on the major etiological agents of winter-ulcers in Atlantic salmon (Salmo salar) in Norway. Outbreaks of ulcerative disease in farmed fish occurs across the North Atlantic region and is an impeding factor for sustainable growth within the industry. Commercially available multivalent core vaccines containing inactivated bacterin of M. viscosa reduce mortality and clinical signs related to winter ulcer disease. Two major genetic clades within M. viscosa have previously been described based on gyrB sequencing, namely typical (hereafter referred to as classic) and variant. Vaccination-challenge trials using vaccines including either variant and or classic isolates of M. viscosa show that classic clade isolates included in current commercial multivalent core vaccines provide poor cross-protection against emerging variant strains, while variant strains confer high level of protection against variant M. viscosa but to a lesser extent to classic clade isolates. This demonstrates that future vaccine regimens should include a combination of strains from both clades.


Computational solutions for omics data.
High-throughput experimental technologies are generating increasingly massive and complex genomic data sets. The sheer enormity and heterogeneity of these data threaten to make the arising problems computationally infeasible. Fortunately, powerful algorithmic techniques lead to software that can answer important biomedical questions in practice. In this Review, we sample the algorithmic landscape, focusing on state-of-the-art techniques, the understanding of which will aid the bench biologist in analysing omics data. We spotlight specific examples that have facilitated and enriched analyses of sequence, transcriptomic and network data sets.


Network-Based Discovery of Opioid Use Vulnerability in Rats Using the Bayesian Stochastic Block Model.
Opioid use disorder is a psychological condition that affects over 200,000 people per year in the U.S., causing the Centers for Disease Control and Prevention to label the crisis as a rapidly spreading public health epidemic. The behavioral relationship between opioid exposure and development of opioid use disorder (OUD) varies greatly between individuals, implying existence of sup-populations with varying degrees of opioid vulnerability. However, effective pre-clinical identification of these sub-populations remains challenging due to the complex multivariate measurements employed in animal models of OUD. In this study, we propose a novel non-linear network-based data analysis workflow that employs seven behavioral traits to identify opioid use sub-populations and assesses contributions of behavioral variables to opioid vulnerability and resiliency. Through this analysis workflow we determined how behavioral variables across heroin taking, refraining and seeking interact with one another to identify potentially heroin resilient and vulnerable behavioral sub-populations. Data were collected from over 400 heterogeneous stock rats in two geographically distinct locations. Rats underwent heroin self-administration training, followed by a progressive ratio and heroin-primed reinstatement test. Next, rats underwent extinction training and a cue-induced reinstatement test. To enter the analysis workflow, we integrated data from different cohorts of rats and removed possible batch effects. We then constructed a rat-rat similarity network based on their behavioral patterns and implemented community detection on this similarity network using a Bayesian degree-corrected stochastic block model to uncover sub-populations of rats with differing levels of opioid vulnerability. We identified three statistically distinct clusters corresponding to distinct behavioral sub-populations, vulnerable, resilient and intermediate for heroin use, refraining and seeking. We implement this analysis workflow as an open source R package, named mlsbm.


Association between sleep duration and obesity is age- and gender-dependent in Chinese urban children aged 6-18 years: a cross-sectional study.
Information on the relationship between sleep duration and obesity among children in urban Guangzhou, China is limited. This study aims to examine the relationship between sleep duration and obesity in children aged 6-18 years. The sample consisted of 11,830 children aged 6-18 years. The children were randomly selected from 13 schools in three urban districts of Guangzhou. The study was conducted from September to November 2013. The height and weight of the children were measured. Adiposity status was estimated using body mass index and according to the cut point in China criteria. In the structured questionnaire, children reported daily sleep hours (less than 7 h, 7-9 h and more than 9 h), weekly food intake amount (including vegetables, fruit, sugar beverages and meat), physical activity and sedentary time. A caretaker would answer the questionnaire on behalf of a child aged below nine. A total of 8,760 children (49.0 % boys) completed the study. The prevalence of obesity was 8.4 % (9.8 % in boys and 5.7 % in girls). Adjusted for age, diet and physical activity/sedentary behaviour, the odds ratio (OR) for obesity comparing sleeping <7 h (short sleep duration, SSD) with ≥9 h (long sleep duration, LSD) was 0.70 (95 % CI: 0.69-0.72) among boys and 1.73 (95 % CI: 1.71-1.74) among girls. Stratified by age, OR for boys aged 6-12 years comparing SSD with LSD was 0.60 (95 % CI: 0.55-0.66); by contrast, OR was 1.33 (95 % CI: 1.30-1.37) for boys aged 13-18 years. Short sleep duration is associated with increased chances of obesity among girls and 13- to 18-year-old boys, but the chances of obesity are decreased among 6- to 12-year-old boys. Age and gender should be regarded as specific characteristics for the effects of short sleep on obesity.


An interpolation method based on adaptive smooth feedrate scheduling and parameter increment compensation for NURBS curve.
Compared with the traditional line/circle interpolation, non-uniform rational B-splines (NURBS) interpolation has more efficient and high-quality advantages in free-form curve/surface modeling. In order to obtain high efficiency and stable interpolation feed motion, a NURBS interpolation method with adaptive smoothing federate scheduling and parameter increment compensation is studied. Firstly, according to the curvature constraint, the adaptive feedrate is obtained and the segmentation of the NURBS curve is completed. Then, in order to avoid the problem of feeding speed overrun, the improved S-shape acceleration/deceleration control is adopted to adjust the jerk. The adjacent segments meeting the combined planning conditions are treated comprehensively. Secondly, aiming at the problem of velocity error in interpolation point parameter calculation, an interpolation parameter calculation method based on parameter increment compensation is proposed to reduce the velocity fluctuation and improve the interpolation point parameter calculation accuracy. Finally, the effectiveness of the proposed method is verified by simulation and experiment. The results show that the algorithm is effective.


L-Sox5 and Sox6 proteins enhance chondrogenic miR-140 microRNA expression by strengthening dimeric Sox9 activity.
Sox9 plays a critical role in early chondrocyte initiation and promotion as well as repression of later maturation. Fellow Sox family members L-Sox5 and Sox6 also function as regulators of cartilage development by boosting Sox9 activation of chondrocyte-specific genes such as Col2a1 and Agc1; however, the regulatory mechanism and other target genes are largely unknown. MicroRNAs are a class of short, non-coding RNAs that act as negative regulators of gene expression by promoting target mRNA degradation and/or repressing translation. Analysis of genetically modified mice identified miR-140 as a cartilage-specific microRNA that could be a critical regulator of cartilage development and homeostasis. Recent findings suggest Sox9 promotes miR-140 expression, although the detailed mechanisms are not fully understood. In this study we demonstrate that the proximal upstream region of pri-miR-140 has chondrogenic promoter activity in vivo. We found an L-Sox5/Sox6/Sox9 (Sox trio) response element and detailed binding site in the promoter region. Furthermore, detailed analysis suggests the DNA binding and/or transactivation ability of Sox9 as a homodimer is boosted by L-Sox5 and Sox6. These findings provide new insight into cartilage-specific gene regulation by the Sox trio.


X-linked dominant inherited diseases with lethality in hemizygous males.
X-linked dominant inheritance with lethality in hemizygous males is a rare mode of inheritance. The three best-known disorders which seem to be inherited in this way, are incontinentia pigmenti (IP) Bloch-Sulzberger, oral-facial-digital I (OFD I) syndrome, and focal dermal hypoplasia (FDH syndrome, Goltz syndrome). It is the purpose of this article to give a review of the clinical and genetic aspects of the above-mentioned diseases and to add those disorders in which this mode of inheritance is discussed. These disorders are: X-linked chondrodysplasia punctata (CP), cervico-oculo-acusticus syndrome (Wildervanck syndrome, COA), congenital cataract with microcornea or slight microphthalmia, muscular dystrophy--hemizygous lethal, partial lipodystrophy with lipatrophic diabetes and hyperlipidemia, Aicardi syndrome, coxo-auricular syndrome, and Johanson-Blizzard syndrome. OTC deficiency is included in the study, although there is no lethality in utero, only in the neonatal period. A critical evaluation of the current literature is carried out.


CNTNAP2 is targeted to endosomes by the polarity protein PAR3.
A decade of genetic studies has established contactin-associated protein-like 2 (CNTNAP2) as a prominent susceptibility gene associated with multiple neurodevelopmental disorders. The development and characterization of Cntnap2 knockout models in multiple species have bolstered this claim by establishing clear connections with certain endophenotypes. Despite these remarkable in vivo findings, CNTNAP2's molecular functions are relatively unexplored, highlighting the need to identify novel protein partners. Here, we characterized an interaction between CNTNAP2 and partitioning-defective 3 (PAR3)-a polarity molecule isolated in a yeast two-hybrid screen with CNTNAP2's C-terminus. We provide evidence that the two proteins interact via PDZ domain-mediated binding, that CNTNAP2+ /PAR3+ complexes are largely associated with clathrin-coated endocytic vesicles in heterologous cells and that PAR3 causes an enlargement of CNTNAP2 puncta size. Live imaging and fluorescence recovery after photobleaching (FRAP) reveals that PAR3 limits the mobility of CNTNAP2. Finally, overexpression of PAR3 but not a PAR3 mutant lacking all PDZ domains (PAR3∆PDZall) can cluster endogenous CNTNAP2 in primary neurons. Collectively, we conclude that PAR3 regulates CNTNAP2 spatial localization.


Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.
This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. Level IV, retrospective therapeutic case series.


Predictors of remission and recovery in a first-episode schizophrenia spectrum disorder sample: 2-year follow-up of the OPUS trial.
To examine the frequency and predictors of good outcome for patients with first-episode schizophrenia spectrum disorder (SSD). We conducted a 2-year follow-up of a cohort of patients (n = 547) with first-episode SSD. We evaluated the patients on demographic variables, diagnosis, duration of untreated psychosis (DUP), premorbid functioning, psychotic and negative symptoms, substance abuse, adherence to medication, and service use. ORs were calculated with logistic regression analyses. A total of 369 patients (67%) participated in the follow-up interview. After 2 years, 36% remitted and 17% were considered fully recovered. Full recovery was associated with shorter DUP, better premorbid adjustment, fewer negative symptoms at baseline, no substance abuse at baseline, and adherence to medication and OPUS treatment. Several predictive factors were identified, and focus should be on potentially malleable predictors of outcome, for example, reducing DUP and paying special attention to patients who are unlikely to achieve good outcome, for example, patients with a substance abuse problem and poor premorbid adjustment.


Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study.
To determine overall survival and factors associated with survival of women with uterine leiomyosarcoma. We performed an observational cohort study of women with uterine leiomyosarcoma (n=7455) from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to investigate predictors of survival. Sensitivity and matched cohort analyses were performed to evaluate the roles of oophorectomy, lymphadenectomy, and chemotherapy in early leiomyosarcoma and chemotherapy in metastatic leiomyosarcoma. Median (interquartile range) age at diagnosis was 54 (48-63) years. Older age, higher comorbidity, black race, higher stage or grade, larger tumor size, lymph node involvement, metastasis at diagnosis, positive surgical margin, adjuvant chemotherapy, and brachytherapy were independently associated with decreased survival by unmatched cohort analyses. Private insurance was associated with increased survival. By matched cohort analyses, omitting oophorectomy was not associated with survival among women≤51years old at diagnosis (event time ratio (ETR) (95% CI) 1.06 (0.90-1.25), P=0.48). Omitting lymphadenectomy was not associated with survival (ETR (95% CI) 1.02 (0.94-1.10), P=0.60). Among women with stage I leiomyosarcoma, adjuvant chemotherapy was not associated with increased survival (ETR (95% CI) 0.91 (0.78-1.05), P=0.18). Chemotherapy was associated with increased survival of women with metastatic leiomyosarcoma (median survival (95% CI) 19.4 (16.4-23.0) versus 10.9 (7.7-14.3) months, ETR (95% CI) 1.66 (1.46-1.90), P<0.001). Early and complete resection is the best-evidenced treatment for uterine leiomyosarcoma. Oophorectomy and lymphadenectomy may be safely omitted for clinically uterus-confined leiomyosarcoma. Chemotherapy increases survival of women with metastatic leiomyosarcoma.


Morphologically constrained and data informed cell segmentation of budding yeast.
Although high-content image cytometry is becoming increasingly routine, processing the large amount of data acquired during time-lapse experiments remains a challenge. The majority of approaches for automated single-cell segmentation focus on flat, uniform fields of view covered with a single layer of cells. In the increasingly popular microfluidic devices that trap individual cells for long term imaging, these conditions are not met. Consequently, most techniques for segmentation perform poorly. Although potentially constraining the generalizability of software, incorporating information about the microfluidic features, flow of media and the morphology of the cells can substantially improve performance. Here we present DISCO (Data Informed Segmentation of Cell Objects), a framework for using the physical constraints imposed by microfluidic traps, the shape based morphological constraints of budding yeast and temporal information about cell growth and motion to allow tracking and segmentation of cells in microfluidic devices. Using manually curated datasets, we demonstrate substantial improvements in both tracking and segmentation when compared with existing software. The MATLAB code for the algorithm and for measuring performance is available at https://github.com/pswain/segmentation-software and the test images and the curated ground-truth results used for comparing the algorithms are available at http://datashare.is.ed.ac.uk/handle/10283/2002. email@example.com. Supplementary data are available at Bioinformatics online.


The end of the message: multiple protein-RNA interactions define the mRNA polyadenylation site.
The key RNA sequence elements and protein factors necessary for 3' processing of polyadenylated mRNA precursors are well known. Recent studies, however, have significantly reshaped current models for the protein-RNA interactions involved in poly(A) site recognition, painting a picture more complex than previously envisioned and also providing new insights into regulation of this important step in gene expression. Here we review the recent advances in this area and provide a perspective for future studies.


Movement-related brain macropotentials during skilled performances. A developmental study.
A developmental study of movement-related brain macropotentials (MRBMs) during a self-paced bimanual skilled performance task (Papakostopoulos 1980) was carried out. MRBMs were obtained from Fpz, Cz and right and left pre-central and electromyograms were recorded from the left and right flexor muscles of the forearms in 30 normal children ranging from 8 to 13 years of age. A consistent Bereitschaftspotential appeared in children of 10 years; in the younger children it was absent or it was positive at precentral and central locations. The motor cortex potential and P200 were present in all children. The skilled performance positivity (SPP), absent at 8 and 9 years, appeared at 11 years of age and was present in older children. The latency of P200 and SPP decreased with age. ANOVA tests showed a statistically significant age effect on performance, EMG rise time and MRBMs; MRBMs were not statistically influenced by time in the experiment: MCP and P200 increased in amplitude with improvement of performance. The results indicate different rates of maturation of the neuronal systems underlying the genesis of the various movement-related brain macropotentials.


Genetic and functional diversity among fluorescent pseudomonads isolated from the rhizosphere of banana.
Fluorescent pseudomonads from banana rhizospheric soil were isolated and screened for the production of enzymes and hormones such as phosphatase, indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC) deaminase, protease, and antifungal metabolites. Of 95 isolates, 50 (52%) isolates solubilized tri-calcium phosphate (TCP), 63 (66%) isolates produced plant growth hormone IAA, 10 (11%) isolates exhibited ACC deaminase, and 23 (24%) isolates produced protease. Isolates were screened for antifungal activity toward phytopathogenic fungi. Gene-specific primers have identified the putative antibiotic producing isolates. These putative isolates were grown in the production media and production of antibiotics was confirmed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Genotypic analysis by BOX (bacterial repetitive BOX element)-polymerase chain reaction (PCR) resulted into three distinct genomic clusters at a 50% similarity level and 62 distinct BOX profiles. Based on the sequence similarity of 16S rRNA and construction of subsequent phylogenetic tree analysis, isolates were designated as Pseudomonas monteilii, P. plecoglossicida, P. fluorescens, P. fulva, P. mosselii, P. aeruginosa, P. alcaligenes, and P. pseudoalcaligenes. Present study revealed the genetic and functional diversity among isolates of fluorescent pseudomonads associated with rhizospheric soil of banana and also identified P. monteilii as dominant species. The knowledge on genetic and functional diversity of fluorescent pseudomonads associated with banana rhizosphere is useful to understand their ecological role and for their utilization in sustainable agriculture.


Efficacy of morantel sustained release bolus against gastrointestinal nematodes in first season grazing Holstein calves.
The efficacy of the morantel sustained release bolus (MSRB) in reducing gastrointestinal parasitism in first season grazing calves was evaluated during the summer--autumn grazing seasons of 1982 and 1983 in western Oregon. Each of 38 calves (1982) and 40 calves (1983) were randomly assigned to either control or treatment groups which were given MSRB on the day of turnout onto pasture. Mean worm burdens from tracer calves grazed with treated animals in 1982 and 1983 showed overall reductions of 86.4% (P greater than 0.05) and 84.3% (P less than 0.01), respectively, compared to tracers grazed with controls. Ostertagia ostertagi, Cooperia oncophora and Nematodirus helvetianus were the primary nematodes collected at necropsy. Twelve full-season 1982 tracer animals (6 treated and 6 control) indicated an 88.1% (P less than 0.05) overall reduction in mean worm burdens. Mean fecal worm egg per gram (EPG) counts of treated animals reflected a reduction of 69% (P less than 0.05) in 1982 and 90% (P less than 0.05) in 1983. Autumn inhibition of O. ostertagi was observed. In the 1982 trial the control animals showed a slight mean weight gain advantage over the treated group from Day 84 until Day 160 (trial termination) when the mean difference was 7.9 kg. The final mean weight gain advantage of treated animals in 1983 was 13.5 kg (P less than 0.05). These trials demonstrated that the MSRB was an effective anthelmintic for reducing gastrointestinal parasitism in grazing calves and for decreasing pasture larval contamination.


Face-to-face clinical skills feedback: lessons from the analysis of standardized patient's work.
Current evidence suggests that trainees are evaluated less stringently when feedback is given face-to-face, limiting its value. We expected that standardized patients (SPs) would also be more lenient in scoring when they gave immediate feedback to the students. Data from 6 clinical skills assessments of students in Years 1 to 4 of medical school were used. Comparisons in scoring were made for the cases on which students received feedback and those where they did not. Analysis was done using a hierarchical linear regression model to test for significant differences. The results indicated no significant difference in scoring for the history and physical exam checklists. There was a small but significant difference on the measure of interpersonal and interviewing skills. The SPs were trained to avoid stringency, leniency, and restricted range in scoring students. These training methods may be useful for training faculty to give face-to-face feedback.


Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis.
Tumoural portal vein thrombosis (PVT) is a major prognostic factor in hepatocellular carcinoma (HCC). The efficacy of sorafenib, the only treatment approved at an advanced stage, is limited. Based on previous data, selective internal radiation therapy (SIRT), or (90)Y radioembolization, seems an interesting option. We aimed to compare both treatments in this population. We retrospectively compared patients treated in two centres for HCC with tumoural PVT. We compared overall survival (OS) between patients treated with SIRT and patients treated with sorafenib. Analyses were performed before and after 1:1 matching with a propensity score for controlling indication bias, using a Cox proportional hazards model. A total of 151 patients were analysed, 34 patients treated with SIRT and 117 patients treated with sorafenib only. In the whole population, SIRT was associated with a higher median OS as compared with sorafenib: 18.8 vs 6.5 months (log-rank p < 0.001). There was an imbalance of baseline characteristics between patients treated by SIRT and sorafenib, which justified patient matching with use of a propensity score: 24 patients treated with SIRT could be matched with 24 patients treated with sorafenib. OS was estimated with a median of 26.2 vs 8.7 months in patients treated with SIRT vs sorafenib, respectively (log-rank p = 0.054). Before and after patient matching, the adjusted hazard ratio related to treatment by SIRT was estimated at 0.62 [95 % confidence interval (CI) 0.39-0.97] (p = 0.037) and 0.40 (95 % CI 0.19-0.82) (p = 0.013), respectively. SIRT seems more effective than sorafenib in patients presenting with HCC and tumoural PVT. This hypothesis is being tested in prospective randomized trials.


Processing of the spectrofluorimetric data using the graphical methods and the maximum likelihood approach.
The present work describes the calculation of the binding constants from spectrofluorimetric data using simple graphical methods and specialized software implementing the maximum likelihood approach. The following popular cases are analyzed: 1) protein-small molecule; 2) protein-metal complex; 3) DNA-small molecule; 4) DNA-metal complex interactions. The inability of graphical plots to return the correct results except for the simplest situation (single reaction with a non-fluorescent product) is demonstrated. The possibility of determining the most probable stoichiometric model using the maximum likelihood estimation (LSQ as its special case) is discussed as well as the limitations.


Cholecystokinin mRNA in porcine cerebellum.
Using previously cloned cDNAs to pig brain prepro-cholecystokinin mRNA and slot blot and S1 nuclease protection assays, the relative cholecystokinin mRNA levels in different regions of the pig brain were measured. The relative amounts of cholecystokinin mRNA generally correlated well with the levels of cholecystokinin-immunoreactive peptides in the various regions tested. One clear exception was noted in the cerebellum; in this region, levels of cholecystokinin mRNA were about 20% of the levels in brain cortex (or second highest level in all areas tested) whereas the mature forms of cholecystokinin peptides (cholecystokinin 58, cholecystokinin 8) were undetectable (less than 3 pmol/g). In vitro translation of cerebellar and cortical cholecystokinin mRNA indicated that there was no difference in the efficiency with which these two RNAs were translated into immunoreactive prepro-cholecystokinin. DNA sequence analysis confirmed that a cloned full-length cerebellar cholecystokinin cDNA was indistinguishable from its cortical counterpart and, therefore, must encode an identical prepro-cholecystokinin. We conclude that there are pronounced regional differences in cholecystokinin expression in pig brain. The apparent discrepancy between levels of immunoreactive cholecystokinin peptides and cholecystokinin mRNA in the cerebellum could be explained by a high turnover rate for the peptides, differential processing of the peptides, or tissue-specific inhibition of cholecystokinin mRNA translation.


Nursing, midwifery, and allied health professions research capacities and cultures: a survey of staff within a university and acute healthcare organisation.
There is an increasing focus on the development of research capacity and culture in Nursing, Midwifery and Allied Health Professions (NMAHP). However, better understanding of the existing research success and skills, motivators, barriers, and development needs of NMAHP professionals is required to inform this development. This study sought to identify such factors within a university and an acute healthcare organisation. An online survey, incorporating the Research Capacity and Culture tool, was administered to NMAHP professionals and students at a university and an acute healthcare organisation in the United Kingdom. Ratings of success/skill levels of teams and individuals were compared between professional groups using Mann-Whitney U tests. Motivators, barriers, and development needs were reported using descriptive statistics. Descriptive thematic analysis was used for open-ended text responses. A total of 416 responses were received (N&M n = 223, AHP n = 133, Other n = 60). N&M respondents were more positive than their AHP counterparts about the success/skill levels of their teams. There were no significant differences between N&M and AHP in their ratings of individual successes/skills. Finding and critically reviewing relevant literature were identified as specific individual strengths; with weaknesses in securing research funding, submitting ethics applications, writing for publication, and advising less experienced researchers. The main motivators for research were to develop skills, increased job satisfaction, and career advancement; whilst barriers included lack of time for research and other work roles taking priority. Key support needs identified included mentorship (for teams and individuals) and in-service training. Open-ended questions generated main themes of 'Employment & staffing', 'Professional services support', 'Clinical & academic management', 'Training & development', 'Partnerships' and 'Operating principles'. Two cross-cutting themes described issues common to multiple main themes: 'Adequate working time for research' and 'Participating in research as an individual learning journey'. Rich information was generated to inform the development of strategies to enhance research capacity and culture in NMAHP. Much of this can be generic but some nuances may be required to address some specific differences between professional groups, particularly related to perceived team success/skills and priorities identified for support and development.


[The combination effect of ampicillin and dicloxacillin on the strains of Bacteriodes fragilis isolated from clinical specimens (author's transl)].
The antimicrobial activities of ampicillin (ABPC) and dicloxacillin (MDIPC) alone were tested in 100 strains of B. fragilis isolated from clinical specimens, and combined activity of ABPC and MDIPC was investigated employing a chequer board titration method (Box method) with agar plates and liquid media. The following results were obtained. 1. Of the 100 strains tested, approximately 33% were shown to have MICs of ABPC greater than 100 mcg/ml, whereas 92% of strains were greater than 100 mcg/ml to MDIPC. 2. In the combination, antimicrobial activities were demonstrated additive or synergistic action in almost strains tested. 3. A combined effect of these drugs was proved by agar dilution method for the strains, for which the same effect was shown by the tube dilution method. 4. For ABPC-resistant strains, no increase in antibacterial activity of these drugs by combination was demonstrated.


A Pharmacokinetic and Pharmacodynamic Investigation of an ε-Aminocaproic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass.
To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α2-antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex). Single-center, tertiary medical center. Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included. None. The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (-0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL. This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA.


Genetic diversity of the Thao people of Taiwan using Y-chromosome, mitochondrial DNA and HLA gene systems.
Despite attempts in retracing the history of the Thao people in Taiwan using folktales, linguistics, physical anthropology, and ethnic studies, their history remains incomplete. The heritage of Thao has been associated with the Pazeh Western plains peoples and several other mountain peoples of Taiwan. In the last 400 years, their culture and genetic profile have been reshaped by East Asian migrants. They were displaced by the Japanese and the construction of a dam and almost faced extinction. In this paper, genetic information from mitochondrial DNA (mtDNA), Histoleucocyte antigens (HLA), and the non-recombining Y chromosome of 30 Thao individuals are compared to 836 other Taiwan Mountain and Plains Aborigines (TwrIP & TwPp), 384 Non-Aboriginal Taiwanese (non-TwA) and 149 Continental East Asians. The phylogeographic analyses of mtDNA haplogroups F4b and B4b1a2 indicated gene flow between Thao, Bunun, and Tsou, and suggested a common ancestry from 10,000 to 3000 years ago. A claim of close contact with the heavily Sinicized Pazeh of the plains was not rejected and suggests that the plains and mountain peoples most likely shared the same Austronesian agriculturist gene pool in the Neolithic. Having been moving repeatedly since their arrival in Taiwan between 6000 and 4500 years ago, the Thao finally settled in the central mountain range. They represent the last plains people whose strong bonds with their original culture allowed them to preserve their genetic heritage, despite significant gene flow from the mainland of Asia. Representing a considerable contribution to the genealogical history of the Thao people, the findings of this study bear on ongoing anthropological and linguistic debates on their origin.


[Bariatric surgery, stomas and other digestive tract reductions: Insufficient data and recommendations to adapt medicines regimens in therapeutic practice].
Surgery modifying digestive tract may alter drugs pharmacokinetics. To maintain concentrations of active substance in their therapeutic ranges, a dosage adjustment or change of drug may be necessary. This is particularly important when no pharmacological or pharmacodynamic parameter reflecting the medication effectiveness is easily measurable. Our objective was to gather the information and documentary tools that can guide prescription in these patients with rearranged digestive tract. We searched information on the documentary portals of French agencies, on gray literature, on MEDLINE and in the summaries product characteristics. No information was found on the website of French agencies, sparse data were identified in gray literature. Some document are discordant, most are imprecise. One hundred and ten studies or case reports referenced on MEDLINE describe 79 medications pharmacokinetics after gastrointestinal surgery. Four are not available in France. Six literature reviews were found. Four summaries of product characteristics provided information related to drug absorption. No documentary tool adapted to clinical routine exists. This unsatisfactory situation is a barrier to optimal patients care. Information is available. It is however necessary to gather under an ergonomic shape adapted to clinical routine, bringing the surgery type, pharmacokinetic changes induced and what to do about the dose adjustment.


[Electron microscopic study of the interaction of influenza virus murine peritoneal macrophages].
Electron microscopic study of mouse peritoneal macrophages infected with influenza virus showed typical phenomena of phagocytosis (absorption, invagination of plasma membrane, and formation of phagosomes) to occur at early stages of virus-cell interaction, up to 2 hours. At later stages, from 3 to 24 hours postinfection, virus particles were completely absent and virus antigen was present in most cells indicating the distruction of phagocytized virus. These observations confirm an important role of macrophages in antiviral immunity.


Persistence of parvovirus B19 in synovial fluid and bone marrow.
To determine whether parvovirus B19 (B19) persists in rheumatoid arthritis (RA). Polymerase chain reaction (PCR) was used to detect parvovirus B19 genome in the synovial fluid cells or peripheral blood mononuclear cells from 61 patients with early RA; bone marrow from one patient was also studied. The synovium or synovial fluid cells from 28 patients with advanced RA, and synovial fluid cell samples from 18 patients with reactive arthritis (as controls) were studied. Two separate sets of primers and probe were used. Parvovirus B19 specific gene sequences were detected in two patients with early arthritis fulfilling the criteria for RA. Parvovirus B19 does not play a significant role in the aetiopathogenesis of RA. However, a few cases of a disease indistinguishable from RA may be triggered by parvovirus B19 infection.


Female splenic-gonadal fusion of the discontinuous type.
Splenic-gonadal fusion is an extremely rare congenital anomaly that results from fusion between the splenic and gonadal anlage during embryonic development. Approximately 90 cases have been reported in the literature. The condition has been divided into two major subgroups: continuous splenic-gonadal fusion in which a continuous cord-like structure connects the spleen and the gonadal-mesonephric structures, and discontinuous splenic-gonadal fusion in which no such connection exists. We report a case of discontinuous splenic-gonadal fusion in an adult women with no evidence of other anomalies or malformations, the fifth reported case of splenic-gonadal fusion occurring in a female. To our knowledge, this is the first case of discontinuous splenic-gonadal fusion reported in a female patient, and the second case of splenic-gonadal fusion reported in an adult woman.


Lewis Acid-Catalyzed Ring-Opening Cross-Coupling Reaction of gem-Difluorinated Cyclopropanes Enabled by C-F Bond Activation.
gem-Difluorinated cyclopropanes have attracted wide research interest in organic synthesis due to their high reactivity. Herein, we report a Lewis acid-catalyzed cross-coupling reaction of mono- and disubstituted gem-difluorinated cyclopropanes with nucleophiles. The formation of a fluoroallyl cation species triggered via the Lewis acid-assisted activation of the C-F bond is proposed in this transformation. The cation species is then trapped by the nucleophiles, including electron-rich arenes and allylsilanes, to deliver a series of fluoroallylic products in good yields. The reaction provides an alternative mode for using gem-difluorinated cyclopropanes as fluoroallyl surrogates.


Thermal pretreatment of Lantana camara for improved biogas production: Process parameter studies for energy evaluation.
The rigid lignocellulosic structure of Lantana camara impedes the hydrolysis phase and reduces the biogas production during anaerobic digestion of Lantana camara. Hence, the current study focuses on the impact of various heating pretreatment techniques, viz., hot air oven (HAO), autoclave (ATC), hot water bath (HWB), and microwave (MCW) on L. camara to speed up hydrolysis and boost up biogas production. ATC pretreatment of L. camara was witnessed to be most efficient compared to HAO, MCW, and HWB pretreatment. ATC pretreatment enhanced the solubilization (45.44%), and an increment in volatile fatty acids (VFA) was observed (56.75%) at 110 °C for 80 min when correlated to the untreated (control). Cumulative methane production following ATC pretreatment had risen to 3656 mL in 5 weeks from 2895 mL in 7 weeks. Thermal pretreatment of Lantana camara broke down the rigid lignocellulosic structure, accelerating the hydrolysis stage and improving biogas production simultaneously. To the best of our knowledge, this is the first thermal pretreatment study conducted on Lantana camara for biogas production.


New AIE-active pyrimidine-based boronfluoride complexes with high solid-state emission and reversible mechanochromism luminescence behavior.
A new family of pyrimidine-based BF2 complexes () with aggregation-induced emission (AIE) and mechanochromic luminescence properties were developed. These compounds exhibit intense fluorescence in their aggregation/solid-state resulting from their large Stokes shift and AIE. X-ray crystallographic analysis shows that the weak intermolecular interactions by fixing the molecular conformations of are responsible for the intense fluorescence in solid-state. In addition to their pronounced AIE behaviour, also exhibits a reversible chromic response to grinding, and a distinct red-shift of emission is observed. The high solid-state luminescence and grinding-stimuli response properties of these compounds make them potential candidates for smart materials.


Cancer risk in Lynch Syndrome.
Lynch Syndrome, or hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by inactivating mutations in DNA mismatch repair genes. It accounts for 2-4 % of all incident colorectal cancers. Mutation carriers are at risk of early onset colorectal cancer, endometrial cancer, and a spectrum of other tumours. Accurate estimation of cancer risk for mutation carriers is essential for counselling, and establishing appropriate screening guidelines. This study reviews the current data on cancer risk, and emerging risk reduction strategies.


[Effect of 8-methoxypsoralen and blacklight on microorganisms in vitro and in experimental trichophytosis in guinea pigs].
The lack of experimental test models causes problems in comparative evaluation of photodynamic effects of 8-MOP and its possible derivatives after irradiation with blacklight or other irradiation sources. In our experiments in vitro, tests with various microorganisms and the in vivo model of experimental dermatophytosis in guinea pigs by Trichophyton mentagrophytes appeared to be suitable. In vivo, 8-MOP was applicated orally and topically in two formulations.


Aberrant right subclavian artery ("arteria lusoria") without the known associated nerve anomaly: an "anomaly of the anomaly"? A clinical case and review of the literature.
The "non-recurrent" course of the inferior laryngeal nerve (ILN) is an anatomical variant which must be borne in mind during thyroid surgery. The "non-recurrent" course of the ILN on the right side is associated with the aberrant right subclavian artery (arteria lusoria), and, on the left, is described in situs viscerum inversus. We present a case in which the "arteria lusoria" was not associated with the non-recurrent right ILN. The aims of this paper are to report this "anomaly of the anomaly" to surgeons who may be unaware of it on the one hand and on the other to emphasize that this is the only case so far reported in the literature. Moreover we proposed to explain embryologically these unexpected findings.


[Adenomatoid cystic lung abnormality in adults with associated bronchioloalveolar carcinoma].
Lung cysts were observed by chance in the chest radiographs from two women aged 20 and 41. In the surgical specimens the lesions proved to be congenital cystic adenomatoid malformation type 1. The cysts were partially lined by mucous cells. Also near the cysts there were circumscribed tubuloacinar proliferations of mucous cells. In both cases a transition into a bronchioloalveolar carcinoma was seen. Histochemically no sulphomucins could be demonstrated by means of an alcian blue pH 1 reaction in the tumor cells, but was demonstrated in the non-neoplastic cells of the malformation. In both cases CEA was demonstrated in the tumor cells. Some cells in the tubuloacinar proliferations were weakly CEA positive. In one patient the diagnosis of carcinoma was made by intraoperative frozen section and a lobectomy was performed. The other patient had first only a resection of her cystic lesions and had to be reoperated because of the results of the pathological examination. Both patients had no recurrence in the 8 years following the operation. In the literature we found 5 cases of congenital cystic adenomatoid malformation in adults. In 2 cases there was also an associated bronchioloalveolar carcinoma. Several reports exist on the association of different kinds of cystic lung lesions and malignant tumors and their possible pathogenetic relationship. In this paper we draw attention to the development of malignant neoplasia in congenital cystic adenomatoid malformation in adults and its diagnostic problems.


A gene between polA and glnA retards growth of Escherichia coli when present in multiple copies: physiological effects of the gene for spot 42 RNA.
We have isolated the single gene for spot 42 RNA of Escherichia coli on a 20-kilobase DNA fragment. Physical characterization of this cloned DNA fragment showed that it is homologous to a region at 86 min on the genetic map and extends from the 23S to 5S rRNA coding region of rrnA to the coding region of glnA, the gene for glutamine synthetase. Other genes included on this cloned DNA fragment are polA, ntrC (glnG), and ntrB (glnL). E coli cells transformed with a multicopy plasmid clone of the gene for spot 42 RNA had about a 10-fold increase in the amount of spot 42 RNA they contained. The amount of 6S RNA in these cells was increased about twofold, although the gene for 6S RNA was not located on this plasmid or on the larger 20-kilobase fragment. Presence of this multicopy plasmid also affected the growth of cells. The generation time was increased under a variety of growth conditions, especially when cells were grown in medium with succinate as the carbon source. In addition, some strains of E. coli which have multicopy plasmids carrying the gene for spot 42 RNA were unable to respond normally to a shift into richer medium: upon upshift from minimal glucose to LB broth or minimal glucose plus 1% Casamino Acids, there was a 3- to 4-h lag before the culture adapted to the new medium. More than 90% of the cells in such cultures stopped dividing, although they remained viable. The plating efficiency of minimal-glucose-grown cells was 100-fold less on rich media than on minimal glucose medium. One revertant was isolated which regained the phenotype of pBR322-transformed cells. Analysis of this strain showed that the plasmid it contained had an insertion of an IS1 element into the 5' end of the coding region for the gene for spot 42 RNA.