[Replacement of the anterior cruciate ligament combined with valgization osteotomy of the tibia in incipient medial gonarthrosis with anterior cruciate ligament insufficiency].
In 7 patients with chronic, primarily anteromedial instability and incipient medial gonarthrosis a procedure combining valgization osteotomy of the tibia with anterior cruciate ligament replacement was employed. Postoperative examinations after observation periods of between 6 months and 5 years revealed that the results were good to very good, both subjectively and objectively. There was either no recurrence or a definite alleviation of knee joint pain present preoperatively. In view of the good results the authors now regard a combination of valgization osteotomy and anterior cruciate ligament replacement as the treatment of choice in cases with clear insufficiency of the anterior cruciate ligament and simultaneous incipient medial gonarthrosis. The combined procedure improves chances of achieving the goal of therapy. A valgization osteotomy or an anterior cruciate ligament replacement alone ought to be regarded as inadequate treatment in such cases, especially in the longer term.


Vitamin D Enhances Immune Effector Pathways of NK Cells Thus Providing a Mechanistic Explanation for the Increased Effectiveness of Therapeutic Monoclonal Antibodies.
Patients with diffuse large cell lymphoma who have an adequate vitamin D supply derive significantly more benefit from immuno-chemotherapy with rituximab than patients with vitamin D deficiency; this is especially true for female patients. We have already been able to show that vitamin D increases the antibody-dependent cytotoxicity (ADCC) of NK cells in a sex-dependent manner, but it is unclear how vitamin D makes NK cells more efficient. Healthy individuals with vitamin D deficiency were supplemented with vitamin D to sufficient levels. NK cells were isolated from blood samples before and after vitamin D saturation. For transcriptome analysis, we used the Affymetrix Gene-Chip 2.0™. Gene expression analysis as well as supervised and unsupervised pathway analysis were performed. Among others the "NK cell-associated cytotoxicity pathway" increased after vitamin D substitution. Five IFN-α subtypes (2, 4, 6, 7 and 10) and IFN-κ were more highly expressed and are mainly responsible in these pathways. In contrast, the pathway "interferon-gamma response", as well as other sets in cytokine production and chemotaxis showed a reduction. Toll-like receptor genes (TLR-8, TLR-7, TLR-2) were downregulated and, therefore, are responsible for the decline of these pathways. The same could be shown for the "ubiquitin-ligase" pathway. Increased expression of several IFN-α subtypes may explain the increased ADCC of NK cells in vitamin D-replenished and otherwise healthy subjects. Other regulators of interferon production and ADCC are compensatory upregulated in compensation, such as Toll-like receptors and those of the ubiquitin ligase, and normalize after vitamin D substitution.


Targeted Gene Disruption in Pacific Oyster Based on CRISPR/Cas9 Ribonucleoprotein Complexes.
The Pacific oyster (Crassostrea gigas) is a representative bivalve mollusc that is widely cultured in the world. In recent years, it has become an important model species for ecological, evolutionary, and developmental studies because of its ability to survive in extreme environmental conditions as a sessile filter feeder and its classical mosaic pattern of development. Although the complete genome sequence of C. gigas is available and omics data have been rapidly generated for the past few years, the genetic tools for gene functional studies have thus far been limited to RNA interference technology. In this study, we developed a gene editing system for C. gigas based on CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 ribonucleoprotein complexes. Two candidate genes, myostatin (MSTN) and Twist, were selected as targets. After microinjecting CRISPR/Cas9 ribonucleoprotein complexes into fertilized eggs, CRISPR-induced indel mutations were detected in the target genes. The CRISPR/Cas9-induced mutations were predominantly small indel mutations ranging in size from 1 to 24 bp in these two target genes. These results demonstrate that CRISPR/Cas9 can be successfully used as an effective targeted gene editing system in C. gigas. The method reported here provides a powerful tool for gene functional studies in oysters and other marine bivalves, and potentially as a new technology for genetic engineering to improve oyster traits for aquaculture.


Hyaluronan injection versus oral glucosamine and diclofenac in the treatment of temporomandibular joint osteoarthritis.
This study was aimed to compare the effects of 4 biweekly hyaluronan (HA) injection with glucosamine and diclofenac oral administration on TMJ OA patients. This retrospective cohort study included TMJ OA patients who had the treatment of 4 biweekly HA injection (group HA) or oral glucosamine hydrochloride for 3 months and diclofenac sodium for 2 weeks (group G/D), and had complete data at first-visit, 3 months, 6 months, and 12 months. Clinical signs and symptoms were scored by anamnestic dysfunction index (Ai) and clinical dysfunction index (Di), and condylar bone changes were evaluated by CBCT scoring system. We included 22 patients in group HA and 20 patients in group G/D. After HA injection, Ai was decreased from 4.3 to 1.6(CI [- 4.0, - 1.4]) at 3-month follow-up, which was smaller than that in group G/D significantly. Di in group HA was declined significantly from 8.1 at first-visit to 3.6 at 3-month follow-up, while Di in group G/D scarcely changed until at 6- and 12-month follow-up. Neither HA injection nor oral glucosamine/diclofenac showed positive effect on the bone of TMJs during follow-ups with statistical significance. HA injection alleviated signs and symptoms of TMJ OA rapidly and presented superior clinical effects over oral glucosamine with diclofenac. However, both treatments did not limit the bone destruction of TMJs significantly. This cohort study provides knowledge on the symptom relief and bone changes of TMJ OA patients when treated with HA injection or glucosamine and diclofenac oral administration.


A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension.
The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n = 6), and patient with hypertension (n = 3), diabetes mellitus (n = 8), and diabetes with hypertension (n = 8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.


Exchange of natural enemies for biological control: is it a rocky road?-the road in the Euro-Mediterranean region and the South American common market.
The access and benefit sharing (ABS) regulations from the Convention on Biological Diversity (CBD) for the use of natural resources became an important issue because the biodiversity of developing countries was heavily accessed and unilaterally exploited by pharmaceutical and seed companies. However, natural enemies used for biological control are living and unmodified genetic resources which cannot be patented and have been treated as resources such as drugs, seeds, or other commercial products. Consequently, the ABS requirements have limited not only the use of natural enemies but also the positive effects that scientifically supported biological control strategies have on the society, the environment, and the economy, reducing problems of pesticide residues, water and soil contamination, and non-target effects. During the last several years, the biological control scientific community has faced new and extremely complicated legislation dictated by a high and diverse number of governmental agencies at different levels, making the access to natural resources for biocontrol purposes a rocky road. Society at large should be aware of how the strict ABS regulations affect the use of natural enemies as biological resources to secure food production, food safety, and global environmental protection. We discuss in here the current difficulties derived from CBD for the exchange of natural enemies taking as example the Euro-Mediterranean region, Argentina, and Brazil to demonstrate how long and diverse are the steps to be followed to obtain the required permits for access and exportation/importation of natural enemies. We then argue that the public visibility of biocontrol strategies should be increased and their benefits highlighted in order to persuade legislators for the development of a less bureaucratic, more expedient, and more centralized regulatory frame, greatly favoring the practice and benefits of biological control. We finally propose a general framework in which ABS issues should be dealt in ways to attend the CBD, but also to make the use of natural resources for the biological control of pests to secure food production and security a possible alternative.


Phytotherapy for Wound Healing: The Most Important Herbal Plants in Wound Healing Based on Iranian Ethnobotanical Documents.
Wound healing is a process that starts with the inflammatory response after the occurrence of any damage. This process initiates by restoring the wound surface coating tissue, migrating fibroblasts to form the required collagen, forming a healing tissue and finally, leading to contortion and extraction of the wound. Today, various drugs are used to heal wounds. However, the drugs used to repair wounds have some defects and side effects. In spite of all attempts to accelerate wound healing definitely, no safe drug has been introduced for this purpose. Therefore, the necessity to identify herbal plants in ethnopharmacology and ethnobotany documents with healing effects is essential. In this article, we tried to review and present effective Iranian medicinal plants and herbal compounds used for wound healing. Searching was performed on databases, including ISI Web of Science, PubMed, PubMed Central, Scopus, ISC, SID, Magiran and some other databases. The keywords used included wound healing, skin treatment, medicinal plants, ethnobotany, and phytotherapy. In this regard, 139 medicinal plants effective on wound healing were identified based on ethnopharmacology and ethnobotanical sources of Iran. Plants such as Salvia officinalis, Echium amoenum, Verbascum spp., G1ycyrrhiza glabra, Medicago sativa, Mentha pulegium, Datura stramonium L., Alhagi spp., Aloe vera, Hypericum perforatum, Pistacia atlantica and Prosopis cineraria are the most important and useful medicinal plants used for wound healing in Iran. These native Iranian medicinal plants are rich in antioxidants and biological compounds and might be used for wound healing and preparation of new drugs.


[Orbital tumors in material of Department of Head and Neck Surgery and Oncological Laryngology of Greater Poland Cancer Center 2007-2010].
Tumors of the orbit are diagnosed sporadically. Based on the tumor registry of the American Cancer Society the incidence of tumors of the orbit is assessed at fewer than 1 per 100 000 persons. Tumors of the orbit can be divided into three groups: primary tumors, tumors penetrating the orbit from neighboring structures, and tumors that are metastases of malignant cancers from distant organs. To present the results of treatment of patients with tumors of the orbit treated in the Head and Neck Surgery and Laryngological Oncology Ward of the Greater Poland Cancer Centre in Poznań during 2007-2010. The study group consisted of 26 patients surgically treated during 2007-2010 in the Head and Neck Surgery and Laryngological Oncology Ward of the Greater Poland Cancer Centre in Poznań. In the postoperative histopathological examination 18 patients (69%) were diagnosed with malignant tumors, 7 patients (27%) with non-malignant tumor and 1 patient (4%) with inflammatory lesion. Among malignant tumors the most frequent was basal cell carcinoma, diagnosed in 7 patients (27%). When removing the tumors of the orbit 4 types of operation were performed: lateral orbitotomy, superior orbitotomy, eye enucleation, and exenteration of the orbit. In 3 patients (12%) cancer recurrences occurred. All patients with recurrences underwent reoperation. In a patient with an extensive recurrence of squamous cell carcinoma the surgery was not radical and the patient died during palliative chemotherapy. Patients with tumors of the orbit should be treated operatively in appropriately prepared centers. In our material the confirmation of this thesis is the group of patients with recurrences of basal cell carcinoma, operated on many times in the past, who due to the extent of the cancerous process had to have the seeing eye removed. In the case of malignant cancers of the orbit an interdisciplinary approach to the problem and the assurance of psychological care for patients who have lost an orbit are essential.


Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis.
The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed for diverse, late-emerging neoplastic fates and linked these to chromatin remodeling at cell-cell communication loci. Using an inference approach, we revealed signaling gene modules and tissue-level cross-talk, including a neoplasia-driving feedback loop between discrete epithelial and immune cell populations that was functionally validated in mice. Our results uncover a neoplasia-specific tissue-remodeling program that may be exploited for pancreatic cancer interception.


The direct role of selenocysteine in [NiFeSe] hydrogenase maturation and catalysis.
Hydrogenases are highly active enzymes for hydrogen production and oxidation. [NiFeSe] hydrogenases, in which selenocysteine is a ligand to the active site Ni, have high catalytic activity and a bias for H2 production. In contrast to [NiFe] hydrogenases, they display reduced H2 inhibition and are rapidly reactivated after contact with oxygen. Here we report an expression system for production of recombinant [NiFeSe] hydrogenase from Desulfovibrio vulgaris Hildenborough and study of a selenocysteine-to-cysteine variant (Sec489Cys) in which, for the first time, a [NiFeSe] hydrogenase was converted to a [NiFe] type. This modification led to severely reduced Ni incorporation, revealing the direct involvement of this residue in the maturation process. The Ni-depleted protein could be partly reconstituted to generate an enzyme showing much lower activity and inactive states characteristic of [NiFe] hydrogenases. The Ni-Sec489Cys variant shows that selenium has a crucial role in protection against oxidative damage and the high catalytic activities of the [NiFeSe] hydrogenases.


[Are the patients not carrying protections after radical prostatectomy really continent?].
To analyse urinary continence and related quality of life in patients not wearing any pad after robotic assisted radical prostatectomy (RARP). Two hundred and sixteen patients operated consecutively by RARP between January 2009 and June 2011 were evaluated by the ICS (International Continence Society) Male Self-questionnaire. The questionnaires were sent by mail and mailed back by patients with a minimum of 14 months following surgery. The ICS questionnaire contains a symptom score (ICS 1) and a quality of life score (ICS 2). Out of 216 sent questionnaires, 145 (67%) were received. The subgroup of 121 patients who replied that they were not wearing any pad was analysed. Fifty-three (43,8%) of them reported not having leakage when coughing or sneezing, 65 (53,7%) reported not having spontaneous leakage, and 102 (84,3%) reported not having leakage when sleeping. The ICS 1 and ICS 2 scores were strongly correlated (Pearson correlation coefficient 0.96). Within a group of patients not wearing any pad following RARP, the continence as assessed by self-questionnaires remains altered. This analysis might help counselling patients who are about to choose a surgical treatment for their prostate cancer.


Unglycosylated rat alpha 1-proteinase inhibitor has a six-fold shorter plasma half-life than the mature glycoprotein.
The plasma half-lives of glycosylated and unglycosylated alpha 1-proteinase inhibitor-radioactively labeled with [35S]methionine in rat hepatocyte primary cultures - were determined in the rat. Unglycosylated alpha 1-proteinase inhibitor was synthesized by hepatocytes in the presence of tunicamycin. Media from hepatocytes containing 35S-labeled glycosylated or unglycosylated alpha 1-proteinase inhibitor were injected into the tail veins of rats. At different times after injection alpha 1-proteinase inhibitor was isolated from plasma by affinity chromatography with anti-alpha 1-proteinase inhibitor Sepharose. Radioactivity measurements revealed a plasma half-life of 170 min for glycosylated alpha 1-proteinase inhibitor and of 30 min for the unglycosylated form of the inhibitor.


AKR1C3 is a biomarker and druggable target for oropharyngeal tumors.
Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets. 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects. Gene set enrichment analysis (GSEA) on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels. We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.


Clinical and radiological profile of neuromyelitis optica spectrum disorders in an Ecuadorian cohort.
Neuromyelitis optica spectrum disorder (NMOSD) is a complex disease characterized by a severe inflammation of the central nervous system (CNS). This disease typically manifests with recurrent optic neuritis (ON) and acute transverse myelitis (ATM). The clinical and radiological spectrum of NMOSD is little known in Latin America (LATAM) and few reports have been published in the literature so far. In Ecuador, no reports on NMOSD have been published. For this reason we aimed to assess the demographic, clinical and imaging characteristics of patients with NMOSD from third level hospitals from Ecuador. This is a descriptive study in which we assessed medical reports of patients with inflammatory demyelinating diseases who were attended in third level hospitals from Ecuador in 2017. Then we applied the 2015 diagnostic criteria, those patients who met the new NMOSD diagnostic criteria were selected and analyzed. Additionally, exploratory sub-analyses were subsequently carried out. We identified 59 patients with NMOSD, the relative frequency of NMOSD was 15.9%. The multiple sclerosis (MS) /NMOSD ratio was 5.2:1. Twenty four percent of patients were newly defined as having NMOSD when 2015 criteria was applied. The median time to diagnoses was shorter by the 2015 criteria than 2006 criteria (p<0.001). NMOSD was more prevalent in women (female/male ratio 4.4:1). The disease onset was more frequent at the fourth decade of life. The most common symptoms at the disease onset were ON and the association of ON with ATM. The mean of expanded disability status scale (EDSS) was 4.8 (SD±1.8). Concomitant autoimmune diseases were infrequent in this population (11.9%). The brain magnetic resonance imaging (MRI) abnormalities were present in 25.7% of patients at disease onset. Spinal cord MRI showed longitudinally extensive transverse myelitis (LETM) in 91.5% of cases. Recurrent NMOSD was frequent in this cohort (88%). Positivity for antibodies against aquaporin-4 (AQP4-IgG) which was measured through indirect immunofluorescence assay (IIF) was identified in 81% of the patients tested. Patients with seronegative AQP4-IgG had higher grade of disability than seropositive patients (p<0.05). Ninety eight percent of patients received treatment with immunosuppressive drugs. Three patients died due to gastric cancer (1 patient) and infectious diseases (2 patients). This is the first descriptive study in an Ecuadorian cohort of patients with NMOSD. We show a wide epidemiological, clinical and radiological spectrum of NMOSD.


Transcript profiling of a MAP kinase pathway in C. albicans.
In Candida albicans, a MAP kinase pathway has been implicated in aspects of controlling hyphal development. We have examined the transcription profile of cells deleted for the transcription factor Cph1p as well as Cst20p, Hst7p, and Cek1p, three upstream kinases potentially involved in Cph1p regulation. Deletion of any of these four elements does not block filament induction by serum and does not dramatically affect the transcription profile of the yeast-hyphal transition, but deletion of CPH1 delays filamentation. Over-expression of Cph1p by ADH1pt-CPH1 significantly enhances filamentation, suggesting that Cph1p is helpful but not essential for filament induction. Interestingly, the transcription profile of ADH1pt-CPH1 expressing cells under yeast conditions is similar to that of wild-type strains undergoing the yeast-hyphal transition. Finally, it appears that Cek1 and its regulators Hst7p and Cst20p may control the repression of genes such as CHT2 through a process independent of the Cph1p transcription factor.


Nutritional regulation of actinomycin-D production by a new isolate of Streptomyces sindenensis using statistical methods.
Production of actinomycin-D, by an isolate, S. sindenensis, was optimized by statistical methods. Fructose peptone and NaNO3 were found to be critical for antibiotic production. In the second step, their concentrations were optimized with Central Composite Design and Response Surface Methodology. Fructose, peptone and NaNO3 at 2.55, 0.309 and 0.114% respectively gave approximately 261% higher yield (289 mg/l). Cultivation in fermentor at 600 rpm agitation and 1.5 vvm aeration with optimized medium gave 3.56 folds higher yield (365 mg/l) as compared to the yields in shake flasks using normal production medium (80 mg/l).


A new proof of evidence of cysteamine quantification for therapeutic drug monitoring in patients with cystinosis.
To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine. The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported. The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.


A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL.
Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific proteins in a proteasome-dependent manner. However, a major limitation of TPD is the lack of E3 ligase recruiters. Recently, we discovered the natural product nimbolide as a covalent recruiter for the E3 ligase RNF114. Here, we show the broader utility of nimbolide as an E3 ligase recruiter for TPD applications. We demonstrate that a PROTAC linking nimbolide to the kinase and BCR-ABL fusion oncogene inhibitor dasatinib, BT1, selectively degrades BCR-ABL over c-ABL in leukemia cancer cells, compared to previously reported cereblon or VHL-recruiting BCR-ABL degraders that show opposite selectivity or, in some cases, inactivity. Thus, we further establish nimbolide as an additional general E3 ligase recruiter for PROTACs, and we demonstrate the importance of expanding upon the arsenal of E3 ligase recruiters, as such molecules confer differing selectivity for the degradation of neo-substrate proteins.


Ventral and dorsal streams for choosing word order during sentence production.
Proficient language use requires speakers to vary word order and choose between different ways of expressing the same meaning. Prior statistical associations between individual verbs and different word orders are known to influence speakers' choices, but the underlying neural mechanisms are unknown. Here we show that distinct neural pathways are used for verbs with different statistical associations. We manipulated statistical experience by training participants in a language containing novel verbs and two alternative word orders (agent-before-patient, AP; patient-before-agent, PA). Some verbs appeared exclusively in AP, others exclusively in PA, and yet others in both orders. Subsequently, we used sparse sampling neuroimaging to examine the neural substrates as participants generated new sentences in the scanner. Behaviorally, participants showed an overall preference for AP order, but also increased PA order for verbs experienced in that order, reflecting statistical learning. Functional activation and connectivity analyses revealed distinct networks underlying the increased PA production. Verbs experienced in both orders during training preferentially recruited a ventral stream, indicating the use of conceptual processing for mapping meaning to word order. In contrast, verbs experienced solely in PA order recruited dorsal pathways, indicating the use of selective attention and sensorimotor integration for choosing words in the right order. These results show that the brain tracks the structural associations of individual verbs and that the same structural output may be achieved via ventral or dorsal streams, depending on the type of regularities in the input.


[Retroperitoneal lesions of the duodenum and pancreas (author's transl)].
The prognosis depends upon timely surgical intervention. Contusions and hematomas of the pancreas are treated through abdominal drainage. Pancreatic duct lesions require resection or pancreaticojejunostomy. Fresh duodenal perforations may be treated by primary suture. In cases of extensive tears, partial gastrectomy combined with selective vagotomy may be the surgical treatment of choice, in rare cases, duodenopancreatectomy. Conservative or surgical treatment of the duodenal hematoma will depend entirely upon the clinical picture.


An evaluation, using computerized image analysis, of antimicrobial efficacy of an automatic hand washing machine with ultrasonic wave spraying.
We studied the antimicrobial efficacy of hand washing with a quick-dry hand washing machine [TE-KIREIKI] employing ultrasonic wave spraying and its incidental alcohol-based product [AROKULIN-E]. The subjects of this study were 10 males who had been instructed not to use any antimicrobial agent for the previous 2 weeks or any hand soap for the previous 5 hours. They pressed their palms on agar before and after washing their hands. After 48-hour incubation at 37 degrees C, the bacterial colonies grown on the agar were counted using the [ASPECT] image processing system. The colony count was expressed as the post-stamp versus pre-stamp percent (%) reduction. Two patterns of hand washing were examined in this study: [A] a 3-second hand wash using an alcohol-based product [AROKULIN-E] and [B] a 30-second hand wash using a nonmedicated detergent soap with running water in addition to hand washing by [A]. The percent (%) reduction after hand washing patterns [A] and [B] were 49.1% and 51.3%. These reduction rates indicated that these patterns did not eradicate bacteria from the hand surface. Therefore, we concluded that this quick-dry hand washing machine employing an ultrasonic wave spraying method combined with an alcohol-based product needs improvement.


Polynuclear cobalt(II/III) sulfites: synthesis, structure, and magnetic properties of the octanuclear cluster (NH4)11(Li subset[Co4IICo4III(SO3)16(NH3)8]).10H2O encapsulating a lithium cation.
Partial oxidation of an aqueous solution of CoIICl(2).6H2O with (NH4)6[Mo7VIO24].4H2O in the presence of (NH4)2SO3.H2O and LiCl, at pH approximately 5.3, leads to isolation of the octanuclear cluster (NH4)11(Li subset[Co4IICo4III(SO3)16(NH3)8].10H2O), 1. The structure of the anion of 1 consists of a central [Co4II], almost ideal square planar unit, and a pair of symmetry-related CoIII dimers above and below the Co4II plane grafting onto the tetramer by 16 bridging sulfite groups. The [Co8(SO3)16(NH3)8]12- cluster encapsulates a lithium cation which lies at the center of the Co4II square.


Three dimensional ballistocardiography: methodology and results from microgravity and dry immersion.
Balistocardiography was recorded in 3-D on a free floating astronaut in space as well as on healthy volunteers participating to a dry immersion study in a terrestrial laboratory. We demonstrate a new technique suitable for the analysis of 3-D BCG. The spatial curve of the displacement vector is analyzed instead of the three components of acceleration. The technique presented is invariant from the axis of representation and provides important novel physiological information.


Symmetrical reactive oligoarthritis after Campylobacter jejuni enteritis--case report and study of the synovial complement.
A 34-year-old man, in whom sacroiliitis had been diagnosed 5 years previously, presented in July 1982 with reactive arthritis following Campylobacter jejuni enteritis. Diarrhoea was stopped by erythromycin but joint effusion recurred. In order to clarify the relationship between Campylobacter jejuni and the immunological system, we proceeded with a study of the synovial complement. The results were compared with those obtained in some other arthropathies.


Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart.
Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.


Tandem Thorpe Reaction/Palladium Catalyzed Asymmetric Allylic Alkylation: Access to Chiral β-enaminonitriles with Excellent Enantioselectivity.
A new type of nucleophile, a 3-imino nitrile carbanion generated in situ by Thorpe reaction of acetonitrile with a base, was developed successfully and applied in a Pd-catalyzed asymmetric allylic alkylation with mono-substituted allyl reagents under Pd/SIOCPhox catalysis, affording β-enaminonitrile products in high yields with excellent regio- and enantioselectivities.


[A clear cerebrospinal fluid - but an unclear diagnosis].
A 35-year-old, previously healthy woman presented with short history of headache and fever. Several other family members reported active hand, foot, and mouth disease. Clinical findings showed subfebrile temperatures and a prominent meningism. Cerebrospinal fluid and computed tomography of the head were unrevealing. Subsequent PCR-analysis of the cerebrospinal fluid was positive for Enteroviral-RNA. Enteroviral-meningitis was diagnosed. The empirically administered antimicrobial therapy was stopped and further diagnostic tests could be withheld. Symptom-oriented therapy resulted in complete resolution within the next few days. Our case emphasizes that, in patients with typical signs of meningeal irritation, normal cellular analysis of the cerebrospinal fluid does not exclude the presence of infectious meningitis. The astute clinician should be reminded that this constellation is highly suggestive of enteroviral meningitis.


An observational study of the cause and frequency of prescription rework in community pharmacies.
When prescriptions are being processed in pharmacies, 'rework' is a phenomenon where an activity occurs that requires the return to a prior procedural step in the process for correction. To date, little is known regarding rework prevalence in community pharmacies or how this might be minimised. To evaluate the cause and frequency of prescription rework in community pharmacies. A list of reworks was designed for community pharmacists to self-record prescription rework instances and causes in their workplace across a two-week period. Community pharmacists in Ireland were recruited via convenience sampling and snowballing. Descriptive statistics were used to assess rework frequency according to the various causes, as well as the pharmacist and pharmacy characteristics. Eight pharmacists participated, recording 325 reworks across 92.9% of the 65 study days (mean 5 reworks/day). The pharmacists' mean ranged from 1.82 to 15 reworks/day. Pharmacists and pharmacy technicians alone or together were involved in 72.3% of reworks. The three most common rework categories were involving labelling errors (22.8%), prepared prescriptions which necessitated opening and repackaging (15.1%), and medication owings to patients (13.9%). This study reveals that prescription rework occurs frequently in community pharmacies and has provided an indication of some of the main causes. These findings demonstrate areas where pharmacy staff can address rework and should aid the development of approaches to minimise rework in future - thus decreasing workload and facilitating more time for community pharmacy staff to focus on providing patient care.


Left thoracotomy utilizing splenectomy in blunt thoracic injury: An alternative surgical approach.
Posterolateral thoracotomy could be an alternative surgical approach in selected cases coexistence of abdominal injuries with ipsilateral thoracic injury. A 65-year-old male with left sided chest injury was initially admitted to a regional health center after a crawler overthrow accident. He underwent chest tube drainage of left hemithorax and he was transferred immediately to our hospital. A CT scan showed a large spleen which was injured by a wedged splint of the 10th rib into its parenchyma. Lung parenchyma was also lacerated by chest tube misplacement with associated hemothorax. He underwent a lower left lateral thoracotomy. Splenectomy was performed via a phrenotomy and subsequently the injured lung was repaired. His postoperative course was uneventful. Incisions in the diaphragm are commonly made to provide adequate exposure during a variety of thoracic and abdominal operations. Thoracic approach could potentially be advantageous for thoracic and abdominal injuries. Thoracic approach is a safe alternative, providing excellent exposure of upper abdominal organs, and should be considered in selected cases of abdominal trauma, especially when an ipsilateral thoracic injury coexists.


Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis.
In 1964 a 42-year-old woman was hospitalized with clinical and laboratory signs of posttransfusion hepatitis five weeks after administration of six whole blood transfusions. During the following 17 years anicteric chronic liver disease was repeatedly documented by elevations of serum aspartate aminotransferase (SGOT) and alkaline phosphatase enzymes. In 1981 hepatomegaly, progressive jaundice, and a serum alphafetoprotein level of 516,000 ng/ml were observed. Percutaneous liver biopsy showed a primary hepatocellular carcinoma (PHC). Serologic examinations failed to reveal markers for hepatitis B virus including HBsAg, anti-HBs, and anti-HBc by radioimmunoassay; antibody to hepatitis A virus was also absent. This sequence of events demonstrates a presumptive association of PHC and the agent(s) of non-A, non-B viral hepatitis.


Chronic Hip Injury Has a Negative Emotional Impact on the Male Athlete With Femoroacetabular Impingement.
To evaluate the impact of hip arthroscopy for femoroacetabular impingement (FAI) on both the physical and mental components of the 36-Item Short Form (SF-36) and assess how changes in health status compare with improvements in physical function and ability to continue to play (CTP) 2 years after surgery. Data collected prospectively from male athletes undergoing primary arthroscopic correction of FAI between November 2008 and October 2016 were analyzed. Physical (PCS) and mental (MCS) component scores of the SF-36 were assessed preoperatively and 2 years postoperatively. The minimal clinical important difference (MCID) was calculated using an anchor-based percentage of possible improvement technique, and the proportion of athletes achieving MCID was established. Logistic regression analysis was used to identify predictors of achieving MCID. CTP was assessed at 2-year follow-up. 486 cases were included, age 25.9 ± 5.6 years. Median PCS improved from baseline 69.4 (51.9 to 85.0) to 91.9 (81.9 to 97.5) at 2 years (P < .001). Median MCS remained unchanged-preoperative, 88 (76 to 92); postoperative, 88 (80 to 96)-although the difference in the distribution of scores was statistically significant (P < .001). Calculated MCID was 60.1% (PCS) and 58.1% (MCS). Mean improvement was significantly higher for PCS compared with MCS (17.4 versus 3.7, P < .001) The proportion of cases achieving MCID was 56.9% and 28.7% for PCS and MCS, respectively, and the difference was statistically significant (P < .001). Lower Tonnis grade (odds ratio [OR] 0.601, 95% confidence interval [CI] 0.377 to 0.958; P = .032) and symptom duration <2 years (OR 0.624, 95% CI 0.406 to 0.960; P = .032) were predictive of achieving PCS MCID. Higher preoperative scores decreased the odds of achieving MCID (OR 0.965, 95% CI 0.955 to 0.975; P < .001; OR 0.972, 95% CI 0.958 to 0.986; P < .001 for PCS and MCS, respectively). 77.3% continued to play their main preinjury sport. Where CTP was not achieved, a significantly higher proportion of cases failed to meet MCID for the MCS compared with PCS (85% versus 60%, P < .001). Arthroscopic management of sports-related FAI results in excellent overall clinical outcome and high levels of satisfaction and CTP at 2 years. Chronic hip injury has a significant negative effect on the physical and mental well-being of athletes; corrective surgery may restore physical function but is more limited in its ability to improve mental health status in this athletic cohort. IV, therapeutic case series.


Experimental Investigation on the Fracture Conductivity Behavior of Quartz Sand and Ceramic Mixed Proppants.
In this paper, a series of fracture conductivity experiments were designed and conducted by an American Petroleum Institute (API) standard fracture conductivity evaluation system. The mixing proportion of quartz sand and ceramic was optimized. By the evaluation of the proppant breakage rate and sphericity analysis of mixed proppant with different sand volume proportions (P S), the proppant mixture conductivity evolution behavior was analyzed. Results of this study showed that the conductivity of mixed proppant was between that of pure ceramic proppant and pure quartz sand proppant under the same conditions. For 20/40 mesh mixed proppant, a small amount of ceramic (25%) in mixed proppant could obtain 1.27-3 times higher conductivity than pure sand, while 40/70 mesh mixed proppant required the addition of 50% or more ceramic. The crushing resistance of mixed proppant determined the decrease of conductivity with the increase of effective closure stresses. A logarithmic empirical model was further derived from the results, which could be used to forecast the performance of fracture conductivity at different effective closure stresses and sand volume proportions.


Poor Diagnostic Efficacy of Noninvasive Tests for Advanced Fibrosis in Obese or Younger Than 60 Diabetic NAFLD patients.
Serum-based noninvasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well-characterized. We analyzed 1489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the areas under the receiver operating characteristic (AUROCs) of Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS), with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM. By histology, 44.0% of the overall cohort (655/1489) had F2-4, and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs NFS 0.676 and HFS 0.682, P = .001) and F3-4 (0.767 vs NFS 0.736 and HFS 0.752, P = .002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI <25 kg/m2), and non-diabetic patients, although overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC, 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC, 0.63-0.66). FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI, and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.


Rapid and sensitive method for the determination of four EU marker polycyclic aromatic hydrocarbons in cereal-based foods using isotope-dilution GC/MS.
A rapid and sensitive method has been developed for the determination of the four European Union marker polycyclic aromatic hydrocarbons (PAHs; benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene) in some cereal-based foods. The method is based on pressurised liquid extraction (PLE), solid-phase extraction clean-up (SPE) and isotope-dilution gas chromatography with mass-spectrometric detection (GC/MS). The developed method was calibrated for the content range of 0.05-12.5 µg kg(-1) (expressed on a product basis). Recoveries of PAH were monitored in each sample via the recovery of (13)C-labelled PAHs. Recovery values were in the range between 86% and 91%, with relative standard deviations (RSDs) between 5% and 9%. The achieved limits of detection for all analytes were below 0.05 µg kg(-1). The applicability of the method for the analysis of routine samples was studied by the analysis of a set of commercial bread and breakfast cereal samples. In all analysed samples, benzo[a]pyrene (BAP) was the most prevalent PAH with the content between 0.09 and 0.30 µg kg(-1). On average, samples showed low levels of the sum of the four EU marker PAHs (ΣPAH4) that ranged between 0.11 and 0.22 µg kg(-1) for bread samples and between 0.23 and 0.87 µg kg(-1) for breakfast cereal samples. The developed method was found suitable for the determination of PAHs in cereal-based foods like cornflakes and breads with total relative fat contents below 3.5%.


Sarcopenia and perioperative management of elderly surgical patients.
Sarcopenia is the age-related loss of skeletal muscle mass, accompanied by reduced muscle strength or physical function. As the global population continues to age, the prevalence of sarcopenia is gradually increasing. It is conceivable that an increasing number of patients with sarcopenia will be scheduled for surgery and anesthesia in the near future. The complex pathogenesis and clinical features of sarcopenia have brought huge challenges to perioperative management, especially in clinical anesthesia. However, there are currently neither guidelines nor expert consensus on the perioperative management of patients with sarcopenia. In this review, we summarize and elaborate on the pathogenesis, diagnosis, and perioperative precautions of sarcopenia, thereby providing information on the perioperative and anesthestic management of patients with sarcopenia.


Maternal mortality in developed countries: not just a concern of the past.
To review the activities in selected developed countries for strategies to identify maternal deaths, the impact of these strategies on underreporting, and the information needed to understand the events leading to death. We reviewed the literature from the United States, Europe, and Australia for publications dealing with maternal death identification and investigation from 1980 to April 1995. We also obtained information directly from researchers involved in major maternal mortality studies. We included all 31 reports (from 14 countries) that discussed methods to improve the ascertainment of maternal deaths beyond the routine use of vital registration. Because of the nature of the subject matter, almost all reports relied on descriptive epidemiology. We found that a variety of methods can be used to improve the ascertainment of maternal deaths, including linkage of birth and fetal death certificates, check-boxes on death certificates, periodic review of deaths of reproductive-age women, and ongoing birth registries and medical audits. Information from a variety of sources is also needed to understand the events leading to death. The numbers of deaths due to pregnancy and its complications are underestimated in most developed countries. Improved ascertainment of maternal death is needed to determine the magnitude of the problem and to assess trends and identify risk groups, allowing development of appropriate and effective strategies to prevent the morbidity and mortality associated with pregnancy.


Investigating the limitations of single breath-hold renal artery blood flow measurements using spiral phase contrast MR with R-R interval averaging.
1) To validate an R-R interval averaged golden angle spiral phase contrast magnetic resonance (RAGS PCMR) sequence against conventional cine PCMR for assessment of renal blood flow (RBF) in normal volunteers; and 2) To investigate the effects of motion and heart rate on the accuracy of flow measurements using an in silico simulation. In 20 healthy volunteers RAGS (∼6 sec breath-hold) and respiratory-navigated cine (∼5 min) PCMR were performed in both renal arteries to assess RBF. A simulation of RAGS PCMR was used to assess the effect of heart rate (30-105 bpm), vessel expandability (0-150%) and translational motion (x1.0-4.0) on the accuracy of RBF measurements. There was good agreement between RAGS and cine PCMR in the volunteer study (bias: 0.01 L/min, limits of agreement: -0.04 to +0.06 L/min, P = 0.0001). The simulation demonstrated a positive linear relationship between heart rate and error (r = 0.9894, P < 0.0001), a negative linear relationship between vessel expansion and error (r = -0.9484, P < 0.0001), and a nonlinear, heart rate-dependent relationship between vessel translation and error. We have demonstrated that RAGS PCMR accurately measures RBF in vivo. However, the simulation reveals limitations in this technique at extreme heart rates (<40 bpm, >100 bpm), or when there is significant motion (vessel expandability: >80%, vessel translation: >x2.2).


Serum levels and liver store of retinol and their association with night blindness in individuals with class III obesity.
Studies showed a rise in obesity prevalence in world population and evidences point to a possible association with vitamin A deficiency (VAD). The objective of this study is to assess vitamin A nutritional status through functional [night blindness diagnosis-xerophthalmia (XN)] and biochemical (serum levels and retinol liver store) indicators of class III obesity individuals and its association. We studied 114 patients of both genders with BMI ≥40 kg/m2, candidates to bariatric surgery at Clínica Cirúrgica Carlos Saboya in Rio de Janeiro, Brazil. XN was diagnosed through a standardized interview (WHO and MacLaren and Frigg), and serum levels and retinol liver store were quantified by HPLC-UV with <1.05 μmol/L and < 20 mg/g cutoffs for VAD, respectively. XN prevalence was 23.8%, and serum levels and retinol liver store inadequacy were 14.0% and 80%, respectively. The association between VAD and XN presence (p = 0.003) was observed with the biochemical indicator and the gold standard, retinol liver store (p = 0.003 and p = 0.018, respectively). Means were 59.3% (sensitivity), 87.4% (specificity), and 80.8% (accuracy) as regards to the XN role in predicting VAD according to the biochemical indicator. As regards to retinol liver store, XN diagnosis presented 48% of sensitivity and 75% of specificity. VAD highest indexes occurred in patients with highest BMI (rs-0.21, p = 0.02). Distribution of XN prevalence was 59.2% according to serum retinol. VAD and XN prevalence was high in class III obesity individuals, and the functional indicator for XN diagnosis may be a promising method for diagnosis in this group.


Disseminating sleep education to graduate psychology programs online: a knowledge translation study to improve the management of insomnia.
Despite the negative impact of poor sleep on mental health, evidence-based insomnia management guidelines have not been translated into routine mental healthcare. Here, we evaluate a state-wide knowledge translation effort to disseminate sleep and insomnia education to graduate psychology programs online using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) evaluation framework. Using a non-randomized waitlist control design, graduate psychology students attended a validated 6-hour online sleep education workshop delivered live as part of their graduate psychology program in Victoria, Australia. Sleep knowledge, attitudes, and practice assessments were conducted pre- and post-program, with long-term feedback collected at 12 months. Seven out of ten graduate psychology programs adopted the workshop (adoption rate = 70%). The workshop reached 313 graduate students, with a research participation rate of 81%. The workshop was effective at improving students' sleep knowledge and self-efficacy to manage sleep disturbances using cognitive behavioral therapy for insomnia (CBT-I), compared to the waitlist control with medium-to-large effect sizes (all p < .001). Implementation feedback was positive, with 96% of students rating the workshop as very good-to-excellent. Twelve-month maintenance data demonstrated that 83% of students had used the sleep knowledge/skills learned in the workshop in their clinical practice. However, more practical training is required to achieve CBT-I competency. Online sleep education workshops can be scaled to deliver cost-effective foundational sleep training to graduate psychology students. This workshop will accelerate the translation of insomnia management guidelines into psychology practice to improve sleep and mental health outcomes nationwide.


Polyendocrine failure with hypogonadism.
Primary gonadal failure, in males with autoimmune endocrinopathies, rarely has been described. We present a unique case of transient hypergonadotropic hypogonadism in a male with type 2 polyglandular failure (Addison's disease and autoimmune hypothyroidism).


Evaluation of urban expansion and the impacts on vegetation in Chinese Loess Plateau: a multi-scale study.
Vegetation degradation caused by rapid urban expansion is a pressing global challenge. Focusing on the Chinese Loess Plateau (CLP), we use satellite observations from 2000 to 2017 to evaluate the spatiotemporal pattern of urban expansion, and its imprint on vegetation across old urban, new urban, urban, non-urban areas as well as the entire urbanization intensity (UI) gradient (from 0 to 100%). We found a massive increase of urban impervious surface area (UISA) in the CLP from 2000 to 2017, and an uneven expansion of UISA at different urban agglomerations and cities. Less green were found in urban and new urban areas, while old urban and non-urban areas generally showed an improved greening pattern. In addition, the annual maximum EVI (EVImax) differences between urban and non-urban areas were - 0.0995 on average from 2000 to 2017. The Guanzhong Plain urban agglomeration (GPUA) witnessed the most significant EVImax differences (- 0.120), and the Ningxia Yanhuang urban agglomeration (NYUA) witnessed the lowest EVImax differences (- 0.012). The EVImax showed significantly decreased trends along the entire spectrum of urbanization gradient for 97.4% (38 of 39) cities and five urban agglomerations. The most significant decrease was found in the GUPA (slope = - 0.0197/10a, p < 0.01), while the smallest drop was found in the NYUA (slope = - 0.011/10a, p < 0.01). This study offered a fundamental support for understanding the vegetation variation along the urban-rural gradient, which may help stakeholders to make better ecological management policies for urban vegetation in ecologically fragile areas.


Comparison of prenatal central nervous system abnormalities with postmortem findings in fetuses following termination of pregnancy and clinical utility of postmortem examination.
In this study, we aimed to compare prenatal ultrasound (USG) and postmortem examination findings of central nervous system (CNS) abnormalities in fetuses following termination of pregnancy (TOP). A total of 190 fetuses with USG-confirmed fetal CNS abnormalities of terminated pregnancies between January 2001 and January 2017 were retrospectively analyzed and USG and postmortem examination findings were compared. The most frequent CNS abnormalities were acrania/anencephaly (n=45, 24%), spina bifida (n=43, 23%), and ventriculomegaly (n=35, 18%). In 144 of the 190 (76%) cases, there was total agreement between USG and postmortem examination diagnosis. Postmortem examination provided minor findings which did not change the major clinical diagnosis in two (1%) cases with spina bifida and ventriculomegaly. In six (3%) cases, the diagnosis changed after postmortem examination. In 25 of the 190 (13%) cases with multiple abnormalities as evidenced by USG, CNS abnormality was unable to be confirmed at postmortem examination. Our study results show an overall high agreement (76%) between USG and postmortem examination findings for CNS malformations. Due to autolysis and fluid structure, USG-confirmed CNS diagnosis cannot be always confirmed by postmortem examination. This potential discrepancy should be explained to patients before considering TOP. Postmortem examination is the gold standard to confirm prenatal diagnosis.


Estimation of vertebral body strength by dual photon absorptiometry in elderly individuals: comparison between measurements of total vertebral and vertebral body bone mineral.
The aim of the present study was to investigate the predictive value of bone mineral measurements by dual photon absorptiometry (DPA) in vitro for strength and ash weight of lumbar vertebral bodies in elderly, otherwise nonselected individuals. The material comprised 46 individuals: 26 males (43-95 years) and 20 females (63-95 years) without malignant diseases. Spinal segments, including L2, L3, and L4, were removed en bloc at autopsy. Bone mineral content (BMC) measurements imitating the normal DPA procedure were performed on the segments suspended in a water bath. The segments were measured in toto (BMCT) and remeasured after removal of the posterior elements (BMCB). The second lumbar vertebral body (L2) was then dissected and sawed below the endplates to obtain samples with planoparallel ends before compression in a materials testing machine. Finally, the bone specimens were incinerated for ash weight estimations. BMCT showed significant correlations to vertebral body ash weight (r = 0.79), compressive strength (load, r = 0.69), and stress (load per unit area, r = 0.47). The correlations were improved by removing the posterior elements (BMCB-ash weight, r = 0.86, BMCB-load, r = 0.74, BMCB-stress, r = 0.49). Correction of BMC for differences in vertebral body height (BMC/cm) further increased the correlation coefficients (BMCB/cm-ash weight, r = 0.92, BMCB/cm-load, r = 0.78, BMCB/cm-stress, r = 0.55). We conclude that lumbar BMC is predictive for lumbar vertebral body compressive strength in vitro and ash weight. The correlation coefficient is improved by removing the posterior non-weight-bearing element.(ABSTRACT TRUNCATED AT 250 WORDS)


Exercise-induced cardiac remodeling.
Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.


Brain cortex phospholipids liposomes effects on CSF HVA, 5-HIAA and on prolactin and somatotropin secretion in man.
Liposomes obtained from bovine brain cortex phospholipids (BC-PL), which display several effects on brain function in mice, have been administered intravenously (200 mg) to healthy subjects at various times before diagnostic lumbar puncture. HVA and 5-HIAA concentrations in CSF have been evaluated with the aim of assessing changes of monoamines metabolism. An increase of HVA occurs after 2 hours from BC-PL administration, reaching its peak after 6--7 hours. The finding is interpreted as an index of an increased turnover of brain DA. 5-HIAA changes are less impressive and a smaller increase of the metabolite is observed. They cannot correctly be related to brain changes of serotonin metabolism, since 5-HIAA originates also from the spinal cord. No effects are observed on the secretion of prolactin, but somatotropin increases sharply between 2 and 7 hours from treatment, suggesting the possibility of an activation of the dopaminergic pathway, stimulating STH secretion.


Spectrophotometric quantitative analysis of remdesivir using acid dye reagent selected by computational calculations.
Remdesivir was approved by the Food and Drug Administration for the treatment of COVID -19 in hospitalized adult and pediatric patients. Application of computational calculations for choosing the sensitive reagent in spectrophotometric quantitative analysis is very limited. Computational and theoretical studies were used for choosing the best acid dye for selective visible spectrophotometric quantitative analysis of remdesivir. The calculations were performed using Gaussian 03 software with the density functional theory method using B3LYP/6-31G(d) basis set. The theoretical studies revealed that bromophenol blue is a better match for remdesivir than other acid dyes due to the higher calculated interaction energy. The proposed method was based on the reaction of remdesivir with the computationally selected acid dye bromophenol blue to form a yellow ion-pair complex. The spectra showed absorption peaks at 418 nm. Various factors affecting the reaction were optimized. The method was successfully applied for the determination of remdesivir in the pharmaceutical preparation with good accuracy and precision. Beer's law was observed in the concentration range of 2-12 μg/mL of remdesivir. The proposed reaction was used as a basis for the spectrophotometric determination of remdesivir in pure form and in the pharmaceutical preparation.


Association between antispasmodics and detection of lesions by screening esophagogastroduodenoscopy.
Whether administration of antispasmodics as a component of premedication contributes to detection of lesions by screening esophagogastroduodenoscopy (EGDS) remains unclear. Our primary aim was to investigate this possibility. The cohort in this retrospective study comprised consecutive asymptomatic individuals who had undergone screening EGDS as part of a health check-up at the Japanese Red Cross Wakayama Medical Center from October 2015 to September 2020. The investigated lesions comprised esophageal squamous cell carcinoma or adenocarcinoma, gastric adenoma or adenocarcinoma, and duodenal adenoma or adenocarcinoma. Targeted lesions were detected in 72 of 31 484 participants (0.23%), 18 260 and 13 224 of whom had received and not received pre-procedure antispasmodics, respectively. The rates of detection of lesions in these groups were 0.21% (38/18260) and 0.26% (34/13224), respectively (P = 0.40). Multivariate logistic regression analysis showed no association between administration of antispasmodics and rates of detection of targeted lesions [P = 0.24, Odds ratio (95% CI): 1.46 (0.78-2.75)]. Antispasmodics, which were administered to more than half of the study cohort, did not improve the rate of detection of targeted lesions.


Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts.
Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases.


Immune response induced by Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides in current and past infectious mononucleosis: a risk for multiple sclerosis?
Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated. Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1(305-320), EBNA1(400-413), from MAP MAP_4027(18-32), MAP_0106c(121-132) and from human proteins IRF5(424-434) and MBP(85-98) in subjects with current and past IM were examined. EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells. Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM.


The role as inoculum sources of Xanthomonas citri pv. citri surviving on the infected Satsuma mandarin fruits.
Importing citrus fruits infected by Asiatic citrus canker caused by Xanthomonas citri pv. citri (Xcc) can act as an inoculum source for the disease epidemic in citrus canker-free countries. In this study, the pathogenicity of the causal agent of Asiatic citrus canker surviving on infected Satsuma mandarin fruits was evaluated. The washing solution of infected Satsuma mandarin fruits did not cause lesion formation on the citrus leaves. However, a typical citrus canker lesion was formed on the leaves after inoculation with higher concentrations of the inoculum from the washing solution (washing solution II). It indicated that the pathogenicity of the citrus canker surviving on the symptomatic Satsuma mandarin fruits was not changed. Scanning electron microscopic observation showed that the numbers of bacterial cells on the leaves of Satsuma mandarin which inoculated with the washing solution directly (washing solution I) was less compared to those of leaves inoculated with the washing solution II. This result spports that the pathogenicity of Xcc surviving on Satsuma mandarin fruits may not be changed but that the sucessful infection of citrus caker may depend on the concentration of the inoculum.


Linkages of antioxidant, micronutrient, and socioeconomic status with the degree of oxidative stress and lens opacity in indian cataract patients.
We assessed the status of micronutrients and oxidative stress in blood and lens and examined their linkages with lens degeneration in cataract patients. For 143 cataract patients (50 to 70 y) and 100 age- and sex-matched controls of low- and high-income groups, oxidative stresses such as as thiobarbituric acid reactive substances (TBARS) and levels of Zn, Fe, Se, Mn, riboflavin, thiamine, vitamin C, vitamin A, beta-carotene, ceruloplasmin, and hemoglobin in plasma were assessed. In extracted cataractous lenses, the ratio of soluble to total proteins (S:T ratio), turbidity, TBARS, and levels of Zn, Fe, Cu, Mn, and Se, were estimated. Plasma TBARS were higher in cataract patients (40% to 66%) than in controls. Levels of hemoglobin and serum ceruloplasmin and plasma levels of Fe, vitamin C, vitamin A, beta-carotene, thiamine, and riboflavin were subnormal in all patients and lowest in low-income patients. Plasma TBARS were positively associated with turbidity (r = 0.30, P < 0.05) but negatively with hemoglobin and ceruloplasmin (r = -0.31 and -0.34, P < 0.05). Plasma malondialdehyde was correlated positively with plasma Se (r = 0.32, P < 0.01), whereas a negative and highly significant correlation was seen with lens Fe (r = -0.53 P < 0.001). Further, plasma TBARS, lens TBARS, and lens turbidity showed significant correlation with opacity grades obtained on a slit-lamp biomicroscope (r = 0.54, 0.37, and 0.34, P < 0.05). The highest S:T ratio was 0.68, indicating a higher threshold for cataract formation in humans. The S:T ratio was negatively associated with lens Fe (r = -0.38, P < 0.001). Turbidity was negatively correlated with Fe levels (r = -0.24, P < 0.001). Oxidative stress of the lens had direct influence on the solubility of lens proteins, leading to an increase in the opacity of lens. Plasma TBARS can be used as biomarkers of degeneration in the lens. Nutritional etiology of cataractogenesis may be different in the two socioeconomic classes.


Decreasing prevalence of isolates with vancomycin heteroresistance and vancomycin minimum inhibitory concentrations ≥2 mg/L in methicillin-resistant Staphylococcus aureus over 11 years: potential impact of vancomycin treatment guidelines.
We evaluated vancomycin MIC (V-MIC) and the prevalence of intermediately susceptible (VISA) and heteroresistant (hVISA) isolates trends in methicillin-resistant Staphylococcus aureus bacteremia among 720 adults (≥ 18 years) inpatients over 4 study periods (2002-2003, 2005-2006, 2008-2009, and 2010-2012). V-MIC (Etest) and the prevalence of hVISA and VISA (determined by population analysis profile-area under the curve) were stratified according to the study period. Mean vancomycin MIC was 1.78 ± 0.39, 1.81 ± 0.47, 1.68 ± 0.26, and 1.54 ± 0.28 mg/L in 2002-2003, 2005-2006, 2008-2009, and 2010-2012, respectively (P < 0.0001). We noted a steadily decreasing prevalence of isolates with V-MIC ≥ 2 mg/L (50.0%, 45.2%, 35.4%, and 18.7%; P < 0.0001) and hVISA (9.7%, 6.6%, 3.0%, and 2.1%; P=0.0003). VISA prevalence remained low (0-2%). These changes coincided with steadily increasing vancomycin trough levels (9.9 ± 7.8, 11.1 ± 8.4, 16.6 ± 7.8, and 19.7 ± 5.9 mg/L in 2002-2003, 2005-2006, 2008-2009, and 2010-2012, respectively; P < 0.0001). These changes imply that adherence to vancomycin treatment guidelines may suppress the development of less susceptible isolates.


Inhibition of sodium transport in frog skin and iodination of tyrosine in vitro by a peptide of renal origin.
Eluates from a Sephadex G-25 column through which dog renal homogenate was passed contained a factor that inhibited lactoperoxidase (LPO)-catalyzed iodination of tyrosine as well as the short circuit current (active absorptive sodium flux) in isolated skin of the bullfrog (Rana catesbeiana). The active fraction also had a sulfhydryl-containing moiety, the concentration of which was correlated directly with the extent of inhibition of the LPO enzyme. The fractions active in inhibition of the LPO enzyme failed to affect the Na/K-AT-Pase enzyme. Whether the same moiety of the active fraction inhibits both the LPO enzyme and SCC in frog skin is unknown and awaits additional study.


Re-localization of nuclear DNA helicase II during the growth period of bovine oocytes.
Nuclear DNA helicase II (NDH II) is the bovine homolog of human RNA helicase A. The aim of this study was to compare NDH II localization between somatic cells (bovine embryonal fibroblasts) and female germ cells (oocytes), with the main focus on the dynamic changes in the redistribution of NDH II during the growth phase of the bovine oocytes. The fine granular staining of NDH II was spread in the whole nucleoplasm of fibroblasts, excluding the reticulated nucleoli. In contrast, the large reticulated nucleoli of the growing oocytes isolated from early antral follicles exhibited strong positivity for NDH II together with the immunostaining signals of upstream binding factor (UBF) and RNA polymerase I subunit (PAF53), documenting the high synthetic activity of these nucleoli. At the time of termination of oocyte growth, NDH II was preferentially located at the nucleolar periphery together with proteins of fibrillar centres. In fully grown oocytes, NDH II was still present in the thin periphery shell around the compact nucleolar core. The semiquantitative RT-PCR revealed that the average signal of NDH II mRNA in fully grown oocytes was only at 40% level in comparison with growing oocytes. Western blot analysis further confirmed that a 140 kD NDH II protein was abundant in growing oocytes, while the signal was substantially weaker in fully grown oocytes. The significant decrease in NDH II gene expression and in NDH II mRNA translation correlates with a termination of the oocyte growth. Altogether, the results demonstrate that NDH II expression parallels the activity of ribosomal RNA biosynthesis in the bovine growing oocytes.


Biological microbeads for flow-cytometric immunoassays, enzyme titrations, and quantitative PCR.
Introduction of microbeads into flow-cytometry has created a new scenario, making quantitative measurement of molecules dispersed in a homogeneous phase, with an extremely wide realm of already realized and potential applications possible. Development of this field has lead to specialized instrumentation and microbead arrays, dedicated to certain applications. Formaldehyde-fixed yeast and bacterial cells were conjugated with avidin and applied as microbeads, to establish a simple, convenient, flexible, and inexpensive flow-cytometric platform for various immunological and biochemical assays. We have tested these "biological microbeads" for the simultaneous titration of human alpha-fetoprotein (AFP) and human Chorionic Gonadotropin (betahCG) hormone levels, for the titration of proteolytic and nucleolytic (restriction) enzymes, and for quantitative PCR, using biotinylated and fluorescent primers. The use of biological microbeads for various immunological and biochemical assays has been demonstrated. The flow-cytometric methods proved to be at least as sensitive as the standard biochemical or immunological tests. For proteinase K activity measurements, a single enzyme molecule in the sample could be detected. The sensitivity, versatility, and low cost of the assays may advance flow-cytometry to become a central methodological platform in most laboratories. The biological microbeads offer virtually unlimited possibilities for fluorescent labeling (addressing), conjugation of ligand binding molecules, and they are easy to handle and perform well in a multiplex format.


Entanglement and teleportation between polarization and wave-like encodings of an optical qubit.
Light is an irreplaceable means of communication among various quantum information processing and storage devices. Due to their different physical nature, some of these devices couple more strongly to discrete, and some to continuous degrees of freedom of a quantum optical wave. It is therefore desirable to develop a technological capability to interconvert quantum information encoded in these degrees of freedom. Here we generate and characterize an entangled state between a dual-rail (polarization-encoded) single-photon qubit and a qubit encoded as a superposition of opposite-amplitude coherent states. We furthermore demonstrate the application of this state as a resource for the interfacing of quantum information between these encodings. In particular, we show teleportation of a polarization qubit onto a freely propagating continuous-variable qubit.


A novel rare sugar inhibitor of murine herpes simplex keratitis.
To determine the therapeutic efficacy of a novel rare sugar, l-psicose, for the treatment of HSV-1 induced herpetic stromal keratitis (HSK) in a mouse eye model. One rare sugar l-psicose was assayed for HSV-1 inhibition of in vitro virus adsorption. The IC50 and IC90 values of l-psicose were determined using plaque reduction assay (PRA) in CV-1 cell. Female Balb/c mice were corneally infected with HSV-1, strain KOS-GFP; A topical eye drop treatment of l-psicose was started 24 h after infection and continued four times daily for ten consecutive days. The severity of HSK was monitored by slit lamp examination in a masked fashion and Infectious HSV-1 shedding was determined by PRA. l-psicose was found to have anti-viral activity in vitro at an IC50 dose of 99.5 mM and an IC90 dose of 160 mM. Topical eye drop treatment with 200 mM l-psicose in PBS solution significantly reduced the severity of HSK compared to the mock treatment group. The in vivo mouse ocular model results of l-psicose therapy correlated with accelerated clearance of virus from eye swabs. The results suggest that topical treatment with rare sugar l-psicose has efficacy against HSK through inhibition of HSV-1.


Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition).
The sixth edition of the Japanese Gastric Cancer Treatment Guidelines was completed in July 2021, incorporating new evidence that emerged after publication of the previous edition. It consists of a text-based "Treatments" part and a "Clinical Questions" part including recommendations and explanations for clinical questions. The treatments parts include a comprehensive description regarding surgery, endoscopic resection and chemotherapy for gastric cancer. The clinical question part is based on the literature search and evaluation by an independent systematic review team. Consequently, not only evidence for each therapeutic recommendation was clearly shown, but it also identified the research fields that require further evaluation to provide appropriate recommendations.


Childhood cardiac function after prenatal diagnosis of intracardiac echogenic foci.
To determine whether prenatally diagnosed intracardiac echogenic foci are associated with childhood cardiac dysfunction and persistence. Children in whom intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center underwent echocardiography at ages 2 to 7 years. A single pediatric cardiologist, blinded to the prenatal sonographic intracardiac echogenic focus locations, assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid and mitral valve regurgitation was also sought. The secondary outcome was intracardiac echogenic focus persistence. Twenty-five children, 14 (56%) male and 11 (44%) female, were examined at a mean age +/- SD of 3.0 +/- 1.0 years. Prenatally, 18 children (72%) had left ventricular intracardiac echogenic foci, and 7 (28%) had right ventricular intracardiac echogenic foci. The left ventricular shortening fraction was normal in all children. The overall mean left ventricular myocardial performance index (reference value, 0.36 +/- 0.06), was normal for both children with left ventricular intracardiac echogenic foci (0.36 +/- 0.06) and those with right ventricular intracardiac echogenic foci (0.36 +/- 0.04). Two children with left ventricular intracardiac echogenic foci had an isolated left ventricular myocardial performance index of greater than 2.5 SD above the mean. Trace tricuspid valve regurgitation and mitral valve regurgitation were noted in 13 (52%) and 2 (8%) of the children, respectively, similar to the general population. Left ventricular intracardiac echogenic foci persisted in 16 children (89%), whereas right ventricular intracardiac echogenic foci persisted in 2 (29%) (P = .007). Prenatally diagnosed intracardiac echogenic foci are often persistent but not associated with childhood myocardial dysfunction.


Knowledge about AIDS and self-reported behaviour among Zimbabwean secondary school pupils.
Knowledge about AIDS and self-reported sexual behaviour was studied among 1532 (893 male, 633 female) Zimbabwean secondary school pupils drawn from 12 schools. Most subjects knew that AIDS is fatal and incurable. However, over 40% of subjects believed that most people with AIDS in Africa are homosexual. Over 40% of respondents did not know that many HIV seropositive individuals look healthy. Nearly 40% of participants believed that HIV can be contracted from toilet seats and 54% of subjects believed that mosquitos can transmit HIV. Pupils from homes in urban areas were better informed about AIDS than were those from homes in rural areas. Forty-six percent of males and nearly 3% of females were reportedly sexually experienced. It is suggested that female under-reporting of sexual activity occurred. Nearly 16% of males reported coital experience with a prostitute. The implications of these findings for future AIDS awareness campaigns in Zimbabwe are considered.


Transdural circumferential decompression for thoracic spinal stenosis caused by beak-type ossification of the posterior longitudinal ligament: a technical note.
Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine is usually progressive and responds poorly to conservative therapy, making surgery the only effective treatment option. A variety of surgical procedures have been developed to treat thoracic OPLL. However, the optimal surgical approach for removal of thoracic OPLL remains unclear. In the present study, we described a newly modified posterior approach for the removal of OPLL: circular decompression via dural approach, and complete removal of OPLL can be achieved under direct vision and without neurological deficit. Three patients with beak-type thoracic OPLL presented with progressive thoracic myelopathy and leg weakness. Magnetic resonance imaging showed the spinal cord severely compressed. The surgical management of the three patients involved the 'cave-in' circular decompression and transdural resection of OPLL. Transdural circumferential decompression was successfully performed in all three patients. Clinical outcome measures, including pre- and postoperative radiographic parameters, were assessed. All of the patients were followed up for an average of 12 months (ranging from 10 to 15 months), and no surgery-related complications occurred. Weakness relief and neural function recovery were satisfactorily achieved in all patients by the final follow-up. Transdural circumferential decompression was an effective method for thoracic spinal stenosis caused by concurrent beak-type OPLL, by which OPLL could be safely removed. It is especially useful when there is a severe adhesion between the dura OPLL.


Gene expression analysis of resistant and susceptible rice cultivars to sheath blight after inoculation with Rhizoctonia solani.
Rice sheath blight, caused by Rhizoctonia solani Kühn (teleomorph: Thanatephorus cucumeris), is one of the most severe diseases in rice (Oryza sativa L.) worldwide. Studies on resistance genes and resistance mechanisms of rice sheath blight have mainly focused on indica rice. Rice sheath blight is a growing threat to rice production with the increasing planting area of japonica rice in Northeast China, and it is therefore essential to explore the mechanism of sheath blight resistance in this rice subspecies. In this study, RNA-seq technology was used to analyse the gene expression changes of leaf sheath at 12, 24, 36, 48, and 72 h after inoculation of the resistant cultivar 'Shennong 9819' and susceptible cultivar 'Koshihikari' with R. solani. In the early stage of R. solani infection of rice leaf sheaths, the number of differentially expressed genes (DEGs) in the inoculated leaf sheaths of resistant and susceptible cultivars showed different regularity. After inoculation, the number of DEGs in the resistant cultivar fluctuated, while the number of DEGs in the susceptible cultivar increased first and then decreased. In addition, the number of DEGs in the susceptible cultivar was always higher than that in the resistant cultivar. After inoculation with R. solani, the overall transcriptome changes corresponding to multiple biological processes, molecular functions, and cell components were observed in both resistant and susceptible cultivars. These included metabolic process, stimulus response, biological regulation, catalytic activity, binding and membrane, and they were differentially regulated. The phenylalanine metabolic pathway; tropane, piperidine, and pyridine alkaloid biosynthesis pathways; and plant hormone signal transduction were significantly enriched in the early stage of inoculation of the resistant cultivar Shennong 9819, but not in the susceptible cultivar Koshihikari. This indicates that the response of the resistant cultivar Shennong 9819 to pathogen stress was faster than that of the susceptible cultivar. The expression of plant defense response marker PR1b gene, transcription factor OsWRKY30 and OsPAL1 and OsPAL6 genes that induce plant resistance were upregulated in the resistant cultivar. These data suggest that in the early stage of rice infection by R. solani, there is a pathogen-induced defence system in resistant rice cultivars, involving the expression of PR genes, key transcription factors, PAL genes, and the enrichment of defence-related pathways. The transcriptome data revealed the molecular and biochemical differences between resistant and susceptible cultivars of rice after inoculation with R. solani, indicating that resistant cultivars have an immune response mechanism in the early stage of pathogen infection. Disease resistance is related to the overexpression of PR genes, key transcriptome factors, and PAL genes, which are potential targets for crop improvement.


The logic behind entrustable professional activity frameworks: A scoping review of the literature.
Entrustable professional activities (EPAs), discrete profession-specific tasks requiring integration of multiple competencies, are increasingly used to help define and inform curricula of specialty training programmes. Although guidelines exist to help guide the developmental process, deciding what logic to use to draft a preliminary EPA framework poses a crucial but often difficult first step. The logic of an EPA framework can be defined as the perspective used by its developers to break down the practice of a profession into units of professional work. This study aimed to map dominant logics and their rationales across postgraduate medical education and fellowship programmes. A scoping review using systematic searches within five electronic databases (Medline, Embase, Google Scholar, Scopus and Web of Science) was performed. Dominant logics of included papers were identified using inductive coding and iterative analysis. In total, 42 studies were included. Most studies were conducted in the United States (n = 22; 52%), Canada (n = 6; 14%) and the Netherlands (n = 4; 10%). Across the reported range of specialties, family medicine (n = 4; 10%), internal medicine (n = 4; 10%), paediatrics (n = 3; 7%) and psychiatry (n = 3; 7%) were the most common. Three dominant logics could be identified, namely, 'service provision', 'procedures' and/or 'disease or patient categories'. The majority of papers (n = 37; 88%) used two or more logics when developing EPA frameworks (median = 3, range = 1-4). Disease or patient groups and service provision were the most common logics used (39% and 37%, respectively). Most programmes used a combination of logics when trying to capture the essential tasks of a profession in EPAs. For each of the three dominant logics, the authors arrived at a definition and identified benefits, limitations and examples. These findings may potentially inform best practice guidelines for EPA development.


Macular pigment is inversely related to circulating C-reactive protein concentrations in school-aged children.
Xanthophyll carotenoids (i.e., lutein and zeaxanthin) are plant pigments that selectively deposit in the macula of the eye and provide retinal tissue with protection against photooxidative stress. Although having greater xanthophylls in various tissues is related to lower inflammation in adulthood and infancy, this relationship is underinvestigated in childhood. Thus, this study aimed to elucidate the relationships between macular xanthophyll status and inflammation in school-aged children. We hypothesized that greater macular pigment would be associated with lower systemic concentrations of C-reactive protein (CRP). Forty children (aged 7-12 years) from the East-Central Illinois area were recruited. Data were collected in a convenience sample over multiple visits to the laboratory that occurred over 1 month, including all individuals who provided adequate blood samples for analyses. Macular pigment optical density (MPOD) was assessed using customized heterochromatic flicker photometry. Dietary lutein and zeaxanthin were determined using 7-day diet records. Capillary dried blood spot samples were analyzed for CRP concentrations via enzyme-linked immunosorbent assay. Whole-body percentage fat (%Fat) was measured using dual-energy x-ray absorptiometry. Two-step hierarchical linear regression modelling was used to assess relationships between MPOD and CRP, following adjustment of pertinent covariates and the removal of outliers (N = 3). MPOD was negatively associated with CRP concentrations, after controlling for a priori covariates of age, sex, %Fat, and dietary lutein and zeaxanthin (β = -0.58, ΔR2 = 0.22, P = .004). Age, sex, dietary lutein and zeaxanthin, and %Fat did not significantly contribute to the model. This study provides novel evidence that macular pigment and peripheral inflammation are inversely related in childhood.


Regional cerebral blood flow in a case of bromide psychosis.
A case of bromide psychosis is described. A course of repeated measurements of the regional cerebral blood flow (rCBF) was followed, using the 133Xe inhalation method. At the first examination, when the serum bromide level was 45 mmol/1, the cerebral blood flow was reduced to about one-third of the normal. The regional flow pattern was also abnormal with low flows in frontal and parieto-occipital regions. Hemodialysis was performed with an overall improvement of the condition and a successive normalization of rCBF. The pronounced decrease of the cerebral blood flow, together with the positive effects of hemodialysis, seems to indicate that bromide psychosis is of a toxic origin and not an abstinence phenomenon.


The adjunct use of descending neurogenic-evoked potentials when transcranial motor-evoked potentials degrade into warning criteria in pediatric spinal deformity surgery: minimizing false-positive events.
This studies objective was to evaluate the utility of descending neurogenic-evoked potentials (DNEPs) in the setting of transcranial motor-evoked potentials (TCeMEPs) degradation into warning criteria during pediatric spinal deformity surgery. An institutional spinal cord monitoring database was queried to identify all primary and revision pediatric spinal deformity cases, < / = 21 years of age performed from 1/2006 to 12/2021, in which TCeMEPs were the primary motor tract assessment modality which degraded into warning criteria, with subsequent initiation of adjunct DNEPs. Fourteen surgical cases (0.42%; 3351 total cases) in fourteen patients met inclusion criteria. Mean age was 13.2 years (7.5-21.3). syndromic (n = 7), kyphosis (n = 3), congenital (n = 2), and idiopathic (n = 2). Three-column osteotomies (3CO)were done in eight patients. TCeMEPs degraded into warning criteria during screw placement (n = 7), 3CO performance/closure (n = 4), or deformity correction (n = 3). DNEPs were present in all cases of warning-criteria TCeMEPs and one case had degradation of DNEPs. Intraoperative Stagnara wake-up tests were performed in only 2/14 cases, with one transient new neurologic deficit (NND). In this specific scenario, DNEPs sensitivity was 50%, specificity 100%, positive predictive value 100%, and negative predictive value 92% to detect aNND. DNEPs were useful in assessing spinal cord function in the setting of TCeMEP data degradation in complex pediatric deformity surgeries. DNEPs demonstrated a higher specificity and positive predictive value in this clinical setting than TCeMEPs when assessing long-term neurologic function after surgery. Based on this small cohort, DNEPs appear to be a useful adjunct modality to TCeMEPs, in this challenging clinical scenario.


Safety and psychological impact of sailing adventure therapy among Veterans with substance use disorders.
Many Veterans suffer from substance use disorders (SUDs). Treatment challenges include poor treatment engagement and high relapse rates. Complementary interventions have the potential to enhance both. This study was a preliminary evaluation of sailing adventure therapy (SAT) for this population. Retrospective chart review. Participants in the intervention were 22 Veterans (20 male, 2 female) aged 22-65 who entered a Veterans Administration residential SUD treatment program. All subjects had two or more SUDs, and many had psychiatric (95%) and/or medical (77%) comorbidities. The age, gender and diagnosis-matched control group (n = 22) received residential SUD treatment as usual (TAU) in the same program but without SAT. Residential SUD treatment program at a Veterans Administration Medical Center. Sailing adventure therapy. Positive and Negative Affect Schedule (PANAS), State Trait Anxiety Inventory six-item short form (STAI: Y-6 item), Acceptance and Action Questionnaire II (AAQ II), Five Facet Mindfulness Questionnaire (FFMQ) and a locally developed patient survey. Outcome comparison among SAT plus TAU group versus TAU - only group included measures of successful completion of residential SUD treatment program as well as psychiatric hospitalizations and/or residential SUD treatment program readmissions within 12 months. Neither physical injuries nor increases in anxiety or negative affect occurred, as measured by the PANAS (positive change, p = 0.351; negative change, p = 0.605) and the STAI: Y-6 item (p = 0.144) respectively. There was no significant change in FFMQ (p = 0.580) but a significant increase occurred in AAQ II scores (p = 0.036) indicating an increase in psychological flexibility. Survey responses indicated the participants perceived the experience to be both pleasurable and calming. The preliminary outcome evaluation revealed a significant between-group difference (X2 = 5.34, DF = 1, p = 0.02, r = 0.35) indicating participating in SAT was associated with a greater likelihood of successfully completing residential SUD treatment. However, there were no significant between-group differences in number of psychiatric hospitalizations (X2 = 1.09, DF = 1, p = 0.29, r = 0.16) or residential substance abuse treatment program readmissions (X2 = 0.23, DF = 1, p = 0.64, r = 0.07) in the 12 months after discharge from the program. Preliminary evidence suggests that SAT is physically safe and not associated with increased anxiety or negative affect. Participant's perceptions of the experience were positive. Preliminary outcome measures suggest associations between participation in SAT and increased psychological flexibility as well as successful completion of a residential SUD treatment program. Further research is indicated to determine whether SAT may be developed as an effective complementary intervention for Veterans with SUDs.