The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.
To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.


Rapid quantification of 3D ultrasound fields with wavefront sensing and Schlieren tomography.
The rapid and precise characterization of three-dimensional (3D) pressure fields inside water is paramount for ultrasound (US) applications in fields as relevant as biomedicine and acoustic trapping. The most conventional way is to scan point-by-point a needle hydrophone across the field of interest, which is an intrinsically invasive and slow process. With typical acquisition times of hours and even days, this method remains impractical in many realistic scenarios. Alternatively, optical techniques can be used to non-invasively and rapidly measure the changes in light intensity or phase induced by pressure differences. However, these techniques remain largely qualitative: extracting precise pressure values can require extensive calibration, and complex processing, or can be limited to low-pressure ranges. Here, we report how combining wavefront sensing and Schlieren tomography enables rapid and direct quantification of 3D pressure fields while obviating any calibration steps. By simultaneously capturing optical phase and intensity information of the US-perturbed fluid using a Wavefront Sensor and Schlieren projections, respectively, 3D pressure fields over several millimeters cubic can be reconstructed after a few seconds. We present a detailed description of the approach and prove its feasibility by characterizing the US field after an acoustic lens, which is in excellent agreement with calibrated hydrophone measurements and simulations. These results are a significant step forward toward the precise and real-time characterization of ultrasound patterns.


Effects of temperature and time on the physical characteristics of moist cakes baked in air fryer.
Baking temperature and time are among the conditions for producing good quality cakes. The aim of this study was to investigate the effects of baking temperature and time on the volume expansion, moisture content, and texture of moist cakes baked in either an air fryer or a convection oven. The cakes were baked under different conditions: (1) baking temperature of 150 °C, 160 °C, and 170 °C for both air fryer and convection oven and (2) baking time of 25, 30, 35 min for air fryer and 35, 40, 45 min for convection oven. Baking temperature and time were found to have a significant (p < 0.05) effect on the relative height, moisture content, firmness and color of the product but no significant effect on the springiness of the product. Based on the numerical optimization method, the optimum condition in an air fryer was 150 °C for 25 min. These optimized conditions resulted in higher relative height (37.19%), higher moisture content (28.80%), lower crumb firmness and chewiness (5.05 N and 1.42 N respectively) as well as higher overall acceptance score (5.70) as compared to optimum condition in convection oven (150 °C at 55 min). Moreover, baking in the presence of rapid air flow in an air fryer may be declared that it is possible to produce high-quality moist cake with minimum baking temperature and shorter baking time.


Relationships among cardiorespiratory fitness, regular physical activity, and plasma lipids in young adults.
Relationships between physical activity and plasma lipids and between cardiorespiratory (CR) fitness and plasma lipids were investigated in 152 young adults. There were no significant correlations in either females or males between the physical activity indicators and any of the plasma lipids investigated. CR fitness, as indicated by treadmill test duration, showed a small but statistically significant sexes, an association that may well underestimate the true relationship because of the limitations of the study. Plasma triglycerides were negatively correlated with CR fitness in the males. It was suggested that the two fitness components, aerobic capacity and percent fat, may be related to certain plasma lipids differently in males than in females.


Evidence for the participation of histidine residues located in the 56 kDa C-terminal polypeptide domain of ADP-ribosyl transferase in its catalytic activity.
Purified ADPRT protein was inactivated by the histidine specific reagent diethylpyrocarbonate, binding to two histidine residues, or by a relatively histidine selective photoinactivation method. Inactivation with up to 1.3 mM diethylpyrocarbonate was reversible by hydroxylamine. Enzymatic inactivation coincided with the loss of binding capacity of the enzyme protein to benzamide affinity matrix but not to DNA cellulose. Labelled diethylpyrocarbonate was identified exclusively in the 56 kDa carboxyl-terminal polypeptide where 2 out of 13 histidine residues were modified by this reagent. It is proposed that histidine residues in the 56 kDa polypeptide may participate as initiator sites for polyADP-ribosylation.


[Haversian remodeling in guided bone regeneration].
To study the relationship between Haversian remodeling and bone regeneration in guided bone regeneration (GBR). 10 mm long segmental defects were created in the diaphyses of one radius in 24 rabbits. The defect was covered with silicone membrane shaped as a tube. Rabbits were killed at the 3rd day, 1st, 2nd, 3rd, 4th, 6th, 10th, 12th weeks. Undecalcified section was prepared for histologic examination. Bone resorption was seen in Haversian canal, connection between osteocytes and osteoblasts in Haversian, and connection of osteoblasts in Haversian and in callus. The process of Haversian remodeling was involved in the process of bone regeneration, just like primary bone healing. The process of Haversian remodeling and regeneration was coupled in topography, time and size. Bone repair is related to Haversian remodeling.


Does early and late life depression differ in residual symptoms, functioning and quality of life among the first-episode major depressive patients.
Age differences exist in many aspects in patients with major depressive disorder (MDD). The present study aims to examine the effect of age on treatment outcomes in first-episode MDD. A total of 982 first-episode major depressive patients, who were above 18 years old and admitted in both psychiatric hospitals and units of general hospitals were recruited for the present study. These patients were newly treated and responded to 8-12 weeks of antidepressant treatment. Depressive symptoms, psychosocial functioning and quality of life were measured using standardized instruments. The study population was divided into three age groups: early adult (18-44 years old), middle adult (45-59 years old), and late adult (60-85 years old). Earlier age was associated with greater symptom severity, severer depressive symptoms in hypersomnia, concentration/decision making, negative view of the self, suicide ideation and restlessness, more impaired function, poorer satisfaction in social relationship and economic status, when compared to late adults with MDD (all P < 0.05). In the multivariable analyses, among the other variables, early age remained as an independent correlation of residual depressive severity (middle age vs. early age: OR = 0.631, 95%CI[0.462, 0.862]; old age vs. early age: OR = 0.521, 95%CI[0.348, 0.780]) and functional impairment. Comorbidity of physical illness had a negative contribution to all treatment outcomes. In first major depressive episode, early age was strongly associated with depressive severity and functional impairment after responding to antidepressant treatment. Early-life depression may be an indicator of MDD for poor clinical outcomes and high clinical burden.


Hypocalcaemia following therapy of thyrotoxicosis in an infant.
A 2-mo-old infant born to a mother with Graves' disease and having symptoms of thyrotoxicosis was started on antithyroid drugs. Life-threatening hypocalcaemia requiring high-dose calcium infusions developed 1 mo after starting therapy. Serum alkaline phosphatase and paratharmone levels were elevated. This communication may serve to alert treating physicians about this rare complication in infants with thyrotoxicosis after initiation of antithyroid therapy. Severe hypocalcaemia may follow initiation of antithyroid therapy in infants with thyrotoxicosis.


Long-haul flights and deep vein thrombosis: a significant risk only when additional factors are also present.
To address the association between travel and deep vein thrombosis (DVT) we examined the risk factors for DVT in 568 consecutive patients with suspected DVT attending King's College Hospital in London. No significant link between DVT and long-haul travel was demonstrable in this cohort, with an odds ratio of 1.3 (CI 0.6-2.8). Risk of DVT was only increased in long-haul travellers if one or more additional risk factors were present, with an odds ratio of 3.0 (CI 1.1-8.2). Such individuals may benefit from prophylactic measures to minimize risk.


Interactions between arsenic migration and CH4 emission in a soil bioelectrochemical system under the effect of zero-valent iron.
Dissimilatory soil arsenic (As) reduction and release are driven by microbial extracellular electron transfer (EET), while reverse EET mediates soil methane (CH4) emission. Nevertheless, the detailed biogeochemical mechanisms underlying the tight links between soil As migration and methanogenesis are unclear. This study used a bioelectrochemical-based system (BES) to explore the potential effects of zero-valent iron (ZVI) addition on "As migration-CH4 emission" interactions from chemical and microbiological perspectives. Voltage and ZVI amendment experiments showed that dissolved As was efficiently immobilized with increased CH4 production in the soil BES, As release and CH4 production exhibited a high negative exponential correlation, and reductive As dissolution could be entirely inhibited in the methanogenic stage. Gene quantification and bacterial community analysis showed that in contrast to applied voltage, ZVI changed the spatial heterogeneity of the distribution of electroactive microorganisms in the BES, significantly decreasing the relative abundance of arrA and dissimilatory As/Fe-reducing bacteria (e.g., Geobacter) while increasing the abundance of aceticlastic methanogens (Methanosaeta), which then dominated CH4 production and As immobilization after ZVI incorporation. In addition to biogeochemical activities, coprecipitation with ferric (iron) contributed 77-93% dissolved As removal under ZVI addition. This study will enhance our knowledge of the processes and microorganisms controlling soil As migration and CH4 emission.


[Evaluation of the relative effectiveness of hybridization probes prepared by action of hydrazides of biotin derivatives on DNA].
Efficiencies of biotinylated DNAs as hybridisation probes in a model system of non-radioactive detection were compared. Probes were obtained by interaction of single-stranded DNA and each of four different hydrazides of biotin derivatives. The most sensitivity in detection of complementary target was obtained using (biocytin hydrazide)-treated DNA. Relations between hydrazide structures and sensitivity of biotinylated probes are discussed.


An empirical typology of subjects within stage of change.
The transtheoretical model of behavior change postulates five distinct, well-defined stages of change: Precontemplation, Contemplation, Preparation, Action, and Maintenance. Each stage has been regarded as reflecting a motivational posture and treated as if it is homogenous with respect to membership. This paper reports the results of four cluster analytic studies, one within each of the first four stages of change. The cluster analysis was based on three constructs of the model. Four distinct subtypes were found within Contemplation, Preparation, and Action, and three subtypes were found within Precontemplation. External validation for the clusters was provided using the 10 Processes of Change and 8 behavioral measures as dependent measures. At least one subtype corresponded to the existing stage definition but the other subtypes suggested alternative intervention strategies.


Inpatient medical-surgical suicidal behavior: a 12-year case-control study.
To describe a medical center's 12-year experience with medically or surgically hospitalized suicide attempters, with the goal of extending the limited literature on this sentinel event. Eight Mayo Clinic Rochester patients' self-inflicting injuries serious enough to trigger mandatory reporting while hospitalized on a medical/surgical unit from January 1, 1998 to December 31, 2010 were matched with four same-sex and same-age controls, admitted to the same unit within 2 months. Cases were identified from Sentinel Event Tracking System and Minnesota Adverse Events Statute records. Data were analyzed with conditional logistic regression. Eight of 777,404 medical/surgical inpatients admitted during 12 years attempted suicide, with significantly more non-Caucasian patients among cases than controls (P=.020). Of 8 attempts, 1 was fatal. More cases than controls had undergone inpatient psychiatric evaluation prior to attempt (P=.020), and elevated risk of attempt was significantly associated with increased number of prior attempts (0.049). Near their attempts, each attempter had an identifiable stressor including inadequately controlled pain in 3, agitation and anxiety in 2 each, and acute delirium, insomnia and psychosocial difficulties in 1 each. First, this study's findings underscore the rarity of reported inpatient medical/surgical suicidal behavior. In this sample, suicide attempters were distinct from nonattempters by the increased likelihood of prior suicide attempts as well as inpatient psychiatric consultations before their attempts. When patients have these characteristics, medical teams should take particular notice and initiate heightened watchfulness for suicidal behavior.


Advances in controlled release pesticide formulations: Prospects to safer integrated pest management and sustainable agriculture.
As the world is striving hard towards sustainable agricultural practices for a better tomorrow, one of the primary focuses is on effective pest management for enhanced crop productivity. Despite newer and potent chemicals as pesticides, there are still substantial crop losses, and if by any means this loss can be tackled; it will alleviate unwanted excessive use of chemical pesticides. Scientific surveys have already established that pesticides are not being utilized by the crops completely rather a significant amount remains unused due to various limiting factors such as leaching and bioconversion, etc., resulting in an adverse effect on human health and ecosystems. Concerted efforts from scientific diaspora toward newer and innovative strategies are already showing promise, and one such viable approach is controlled release systems (CRS) of pesticides. Moreover, to bring these smart formulations within the domain of current pesticide regulatory framework is still under debate. It is thus, paramount to discuss the pros and cons of this new technology vis-à-vis the conventional agrarian methods. This review deliberates on the developmental updates in this innovative field from the past decades and also appraises the challenges encumbered. Additionally, critical information and the foreseeable research gaps in this emerging area are highlighted.


Distinct influences of nerve growth factor and a central cholinergic trophic factor on medial septal explants.
A central cholinergic trophic factor (C-CTF), previously reported in hippocampal extracts, enhances acetylcholine synthesis (ACh) and to a lesser extent choline acetyltransferase (ChAT) activity in cultured explants of the rat medial septal nucleus. Nerve growth factor (NGF) has been reported to enhance ChAT in several systems in vitro and in vivo, and clearly stimulates septal explants. At optimal concentrations of NGF and C-CTF, there is an additive effect on ChAT activity. The effects of NGF on ACh synthesis are minimal. Antibodies to NGF block effects of added NGF but have no effects on C-CTF activity. The ability of C-CTF to enhance ACh synthesis appears related to its ability to enhance the acetylation of the choline that has been taken up by a sodium dependent, high affinity transport system. Thus, actions of NGF and C-CTF appear qualitatively and quantitatively distinct, yet both can influence the cholinergic activity of the developing medial septal nucleus.


SEM, EDS and XPS Analysis of the Coatings Obtained on Titanium after Plasma Electrolytic Oxidation in Electrolytes Containing Copper Nitrate.
In the paper, the Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Photoelectron Spectroscopy (XPS) results of the surface layer formed on pure titanium after plasma electrolytic oxidation (micro arc oxidation) at the voltage of 450 V are shown. As an electrolyte, the mixture of copper nitrate Cu(NO₃)₂ (10-600 g/L) in concentrated phosphoric acid H₃PO₄ (98 g/mol) was used. The thickness of the obtained porous surface layer equals about 10 μm, and it consists mainly of titanium phosphates and oxygen with embedded copper ions as a bactericidal agent. The maximum percent of copper in the PEO surface layer was equal to 12.2 ± 0.7 wt % (7.6 ± 0.5 at %), which is the best result that the authors obtained. The top surface layer of all obtained plasma electrolytic oxidation (PEO) coatings consisted most likely mainly of Ti₃(PO₄)₄∙nH₃PO₄ and Cu₃(PO₄)₂∙nH₃PO₄ with a small addition of CuP₂, CuO and Cu₂O.


Intra-Operative Indocyanine Green Angiography of the Parathyroid Gland.
Major complications of thyroid and parathyroid surgery are recurrent laryngeal nerve injuries and definitive hypoparathyroidism. The use of intra-operative Indocyanine Green Angiography for confirmation of vascular status of the parathyroid gland is reported here.


[Transoral microsurgical treatment of craniocervical malformation].
To discuss transoral microcervical treatment of 16 patients with craniocervical malformation. Perioperative treatment including antibiotics, tracheotomy, intravenous nutrition was used in 16 patients. Eight patients had basilar impressions, 3 chronic atlantoaxial dislocation and 2 odontoid fracture, 2 lower clivus chordoma, and 1 granuloma in the ventral part of the medulla oblongata. Three patients received bone graft. Follow-up for 6 - 36 months showed that 14 patients resumed normal life but 1 died. Pre-craniocervical malformation can be treated by transoral approach microsurgically. Understanding microanatomy of this approach can reduce postoperative morbidity and complications. Perioperative treatment can prevent incision infection. Prevention of intraoperative CSF leakage must be emphasized.Bone graft can make craniocervical spine stable.


Retroperitoneal laparoscopic nephrectomy: initial case report.
Pre-transplant nephrectomy was done in a 25-year-old man for calculous pyelonephritis using a retroperitoneal laparoscopic approach with a newly devised ligature applicator-dissector- kidney retractor.


COMT polymorphisms affecting protein expression are risk factors for endometrial cancer.
In estrogen metabolic pathways, the COMT enzyme is related to detoxification. COMT gene polymorphisms have been shown to effect enzyme function. We hypothesized that these polymorphisms may be risk factors for endometrial cancer (EC). DNA samples from 150 cases of EC and healthy controls (n = 165) were analyzed by PCR-RFLP to determine the genotypic frequency of four different polymorphic loci on COMT [codon 62 (rs4633), 102 (rs5031015), 136 (rs4818), 158 (rs4680)]. Genotyping was confirmed by direct DNA sequencing. We also conducted haplotype analysis of COMT and investigated the relationship between COMT expression and COMT SNPs in EC tissues by immunohistochemistry. A significant increase in the T/T genotype of codon 62 (C/T) was observed in patients compared to controls (OR = 2.39, 95% CI: 1.31-4.37, P = 0.004). The frequency of the C-G haplotype of codon 62 C/T and codon 158 G/A was significantly higher in controls (P < 0.0001) than in patients. The expression level of COMT protein in EC tissues was significantly lower in COMT codon 62 variant TT and codon 158 variant AA genotype carriers. Therefore, the EC samples with polymorphic variants of COMT lead to lower expression of COMT protein whereas EC samples with wild-type codon 62 C/C and codon 158 G/G have higher expression of COMT protein. This is the first study demonstrating that polymorphisms in COMT codon 62 and codon 158 altered protein expression levels in EC, suggesting that they may be risk factors for EC in Caucasians.


Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+-ATPase.
Surface-expressed Na+/K+-ATPase (NaK) has been suggested to function as a non-canonical cardiotonic steroid-binding receptor that activates multiple signaling cascades, especially in cancer cells. By contrast, the current study establishes a clear correlation between the IC50in vitro growth inhibitory concentration in human cancer cells and the Ki for the inhibition of activity of purified human α1β1 NaK. The in vitro growth inhibitory effects of seven cardiac glycosides including five cardenolides (ouabain, digoxin, digitoxin, gitoxin, uzarigenin-rhamnoside, and their respective aglycone forms) and two bufadienolides (gamabufotalin-rhamnoside and hellebrin, and their respective aglycone forms) were determined by means of the MTT colorimetric assay and hellebrigenin-induced cytotoxic effects were visualized by means of quantitative videomicroscopy. The binding affinity of ten of the 14 compounds under study was determined with respect to human α1β1, α2β1 and α3β1 NaK complexes. Lactate releases and oxygen consumption rates were also determined in cancer cells treated with these various cardiac glycosides. Although cardiotonic steroid aglycones usually display weaker binding affinity and in vitro anticancer activity than the corresponding glycoside, the current study demonstrates that the hellebrin / hellebrigenin pair is at odds with respect to this rule. In addition, while some cardiac steroid glycosides (e.g., digoxin), but not the aglycones, display a higher binding affinity for the α2β1 and α3β1 than for the α1β1 complex, both hellebrin and its aglycone hellebrigenin display ~2-fold higher binding affinity for α1β1 than for the α2β1 and α3β1 complexes. Finally, the current study highlights a common feature for all cardiotonic steroids analyzed here, namely a dramatic reduction in the oxygen consumption rate in cardenolide- and bufadienolide-treated cells, reflecting a direct impact on mitochondrial oxidative phosphorylation. Altogether, these data show that the binding affinity of the bufadienolides and cardenolides under study is usually higher for the α2β1 and α3β1 than for the α1β1 NaK complex, excepted for hellebrin and its aglycone form, hellebrigenin, with hellebrigenin being as potent as hellebrin in inhibiting in vitro cancer cell growth.


Endodermal sinus (yolk sac) tumors in pediatric oncology. Report on 14 cases.
Fourteen cases of the endodermal sinus tumors in children are reported. The most frequent localization was the vagina, next presacral region, ovary and testis. No ovarian case was observed under 3 years of age.


[Achievements of molecular endocrinology and biochemistry of hormones and new approaches to the study and correction of endocrine disorders].
Considerable progress in a study of the molecular mechanisms of the hormone biological effect has shown that practically all hormones regulate metabolism in the body by influencing the cell genetic system. These fundamental results served as a basis for a rapid development of a new direction--molecular endocrinology. In recent years effective approaches that make it possible to penetrate the secret of human and animal gene structure have been worked out. The paper is concerned with the results of a study of nucleotide sequences of genes and mRNA of various protein hormones and an analysis of the importance of these developments for present-day endocrinology and biochemistry of hormones.


How to phase II: Timelines, perceptions, and suggestions from PGY-1 residency program directors.
Phase II was implemented in 2016 to provide structure for applicants and unmatched residency pharmacy programs to interact. Previous literature has provided some approaches for this process; however, clarification on navigating the phase II process to successfully match for applicants and their mentors is still needed. In addition, with phase II occurring for >6 years, there is a need for continual evaluation. The objectives were to describe (1) program phase II structure and timelines, (2) program personnel demand, and (3) perceptions of and suggestions for phase II from postgraduate year (PGY)1 residency program directors (RPDs) to provide clarity to applicants, mentors, and residency stakeholders. A 31-item survey was developed including 9 demographic items, 13 program-specific timeline-based items, 5 skip-logic items on screening interviews, and 4 qualitative questions on the benefits, drawbacks, and suggested changes to phase II. The survey was disseminated to PGY-1 RPDs participating in phase II with available contact information in June 2021 and May 2022, with 3 weekly reminders. The survey was completed by 180 of the 484 RPDs participating in phase II (37.2% response rate). Programs participating in the survey had an average of 1.4 positions (± 0.7) open in phase II and 31 applicants (± 31) per open position. The timelines for screening applications, contacting applicants, and conducting interviews were variable. For qualitative data, RPDs appreciated the structured process and noted high-quality and geographic diversity of applicants in phase II. However, challenges reported were the quantity of applications, lack of time to fully review applications, and technical issues. Suggested changes included an extended phase II timeline, universal application deadline, and technical improvements. The structured approach of phase II was an improvement compared with historical approaches; however, variability exists in timelines for programs. Respondents identified further opportunities to refine phase II to benefit residency stakeholders.


6D-QSAR for predicting biological activity of human aldose reductase inhibitors using quasar receptor surface modeling.
The application of QSAR analysis dates back a half-century ago and is currently continuously employed in any rational drug design. The multi-dimensional QSAR modeling can be a promising tool for researchers to develop reliable predictive QSAR models for designing novel compounds. In the present work, we studied inhibitors of human aldose reductase (AR) to generate multi-dimensional QSAR models using 3D- and 6D-QSAR methods. For this purpose, Pentacle and Quasar's programs were used to produce the QSAR models using corresponding dissociation constant (Kd) values. By inspecting the performance metrics of the generated models, we achieved similar results with comparable internal validation statistics. However, considering the externally validated values, 6D-QSAR models provide significantly better prediction of endpoint values. The obtained results suggest that the higher the dimension of the QSAR model, the higher the performance of the generated model. However, more studies are required to verify these outcomes.


Quantitative phosphoproteomic analysis of early seed development in rice (Oryza sativa L.).
Rice (Oryza sativa L.) seed serves as a major food source for over half of the global population. Though it has been long recognized that phosphorylation plays an essential role in rice seed development, the phosphorylation events and dynamics in this process remain largely unknown so far. Here, we report the first large scale identification of rice seed phosphoproteins and phosphosites by using a quantitative phosphoproteomic approach. Thorough proteomic studies in pistils and seeds at 3, 7 days after pollination resulted in the successful identification of 3885, 4313 and 4135 phosphopeptides respectively. A total of 2487 proteins were differentially phosphorylated among the three stages, including Kip related protein 1, Rice basic leucine zipper factor 1, Rice prolamin box binding factor and numerous other master regulators of rice seed development. Moreover, differentially phosphorylated proteins may be extensively involved in the biosynthesis and signaling pathways of phytohormones such as auxin, gibberellin, abscisic acid and brassinosteroid. Our results strongly indicated that protein phosphorylation is a key mechanism regulating cell proliferation and enlargement, phytohormone biosynthesis and signaling, grain filling and grain quality during rice seed development. Overall, the current study enhanced our understanding of the rice phosphoproteome and shed novel insight into the regulatory mechanism of rice seed development.


Alteration of floral organ identity in rice through ectopic expression of OsMADS16.
We used a transgenic approach and yeast two-hybrid experiments to study the role of the rice ( Oryza sativa L.) B-function MADS-box gene, OsMADS16. Transgenic rice plants were generated that ectopically expressed OsMADS16 under the control of the maize ( Zea mays L.) ubiquitin1 promoter. Microscopic observations revealed that the innermost-whorl carpels had been replaced by stamen-like organs, which resembled the flowers of the previously described Arabidopsis thaliana (L.) Heynh. mutation superman as well as those ectopically expressing the AP3 gene. These results indicate that expression of OsMADS16 in the innermost whorl induces stamen development. Occasionally, carpels had completely disappeared. In addition, ectopic expression of OsMADS16 enhanced expression of OsMADS4, another B-function gene, causing superman phenotypes. In the yeast two-hybrid system, OsMADS16 did not form a homodimer but, rather, the protein interacted with OsMADS4. OsMADS16 also interacted with OsMADS6 and OSMADS8, both of which are homologous to SEPALLATA proteins required for the proper function of class-B and class-C genes in Arabidopsis. Based on the gene expression pattern and our yeast two-hybrid data, we discuss a quartet model of MADS-domain protein interactions in the lodicule and stamen whorls of rice florets.


Musculoskeletal disorders in neonatal foals.
Angular limb deformities are not uncommon in foals. Mild angular deviation due to laxity of supporting soft tissues often resolves spontaneously. However, external splinting or casting may be needed in severe cases or in those that do not resolve. When incomplete ossification of carpal or tarsal bones is the cause of the limb deformity, external support is mandatory to prevent further deformation and abnormal development of the bones. When epiphyseal and metaphyseal abnormalities cause axial deviation, surgical intervention is usually necessary. Circumferential periosteal transection and/or transphyseal bridging are methods used. The choice is dictated by the type and severity of the deformity. Flexor contractures of the forelimb vary greatly in degree and joints affected. Physical therapy combined with intermittent splint application is often successful, but surgical intervention may be necessary in unresponsive cases. Flexor tendon laxity is usually self-correcting but physical therapy, restricted exercise, and splinting may be needed. Rotational abnormalities are easier to correct in the forelimbs than in the hind limbs. Correction is usually accomplished by frequent corrective hoof trimming. Miscellaneous anomalies of the musculoskeletal system may sometimes be amenable to surgical correction, although the potential disadvantages must be carefully considered. Septic arthritis is a frequent sequela to neonatal septicemia and must be treated aggressively and early in its development. Appropriate systemic antibiotics, joint lavage, and rest are indicated. Neonatal osteomyelitis has a poor prognosis and requires prompt, vigorous therapy; even then, growth anomalies of the limb or contiguous septic arthritis may develop and further worsen the prognosis. Early accurate diagnosis and prompt appropriate therapy are vital in treating musculoskeletal disorders in foals, especially when a successful outcome is judged by the animal becoming a functional athlete.


Tyrosine phosphorylation and the regulation of cell growth: growth factor-stimulated tyrosine phosphorylation of phospholipase C.
The significance of tyrosine phosphorylation in cell growth and transformation has been addressed. While the details of how tyrosine kinases actually function in mitogenic signal transduction is not fully understood, recent evidence suggests that phosphoinositide metabolism may have a significant role in growth factor signal transduction. Interestingly, one of phosphatidylinositol-specific phospholipase C isozymes is an excellent substrate for growth factor receptor tyrosine kinases. In this review, the current understanding of growth factor-mediated phosphoinositide metabolism and tyrosine phosphorylation of phospholipase C, is discussed.


Solution secondary structure of calcium-saturated troponin C monomer determined by multidimensional heteronuclear NMR spectroscopy.
The solution secondary structure of calcium-saturated skeletal troponin C (TnC) in the presence of 15% (v/v) trifluoroethanol (TFE), which has been shown to exist predominantly as a monomer (Slupsky CM, Kay CM, Reinach FC, Smillie LB, Sykes BD, 1995, Biochemistry 34, forthcoming), has been investigated using multidimensional heteronuclear nuclear magnetic resonance spectroscopy. The 1H, 15N, and 13C NMR chemical shift values for TnC in the presence of TFE are very similar to values obtained for calcium-saturated NTnC (residues 1-90 of skeletal TnC), calmodulin, and synthetic peptide homodimers. Moreover, the secondary structure elements of TnC are virtually identical to those obtained for calcium-saturated NTnC, calmodulin, and the synthetic peptide homodimers, suggesting that 15% (v/v) TFE minimally perturbs the secondary and tertiary structure of this stably folded protein. Comparison of the solution structure of calcium-saturated TnC with the X-ray crystal structure of half-saturated TnC reveals differences in the phi/psi angles of residue Glu 41 and in the linker between the two domains. Glu 41 has irregular phi/psi angles in the crystal structure, producing a kink in the B helix, whereas in calcium-saturated TnC, Glu 41 has helical phi/psi angles, resulting in a straight B helix. The linker between the N and C domains of calcium-saturated TnC is flexible in the solution structure.


Biomonitoring of radioactive contamination of the Yenisei River using aquatic plants.
The Yenisei River is contaminated by artificial radionuclides released by one of the Russian facilities producing weapons-grade plutonium (the Mining-and-Chemical Combine, MCC), which has been in operation for 60 years. The paper presents results of long-term monitoring of radionuclide concentrations in six aquatic plant species collected from the 1400 km Yenisei River stretch downstream of the city of Krasnoyarsk. Before the last MCC reactor was shut down (in 2010), up to 30 artificial radionuclides were detected in the plant biomass, and 2 and 5 years after the reactor shutdown, 11 and 3-5 radionuclides, respectively, were detected. The highest concentrations of radionuclides were recorded in Fontinalis antipyretica. The aquatic plant Elodea canadensis, which commonly occurs in the Yenisei River, was used in the cytogenetic study. High frequencies of chromosomal aberrations (up to 33%) were revealed in cells of Elodea canadensis roots from the Yenisei region affected by the MCC radioactive discharge, at dose rates of 45-72 μGy/d, while in the cells of the plant roots from the reference areas, the frequency of chromosomal aberrations was 5-7%, at dose rates below 2 μGy/d. The higher frequencies of chromosomal aberrations in Elodea canadensis collected from the parts of the River with increased concentrations of artificial radionuclides are associated with the radiation factor. The aquatic plant Elodea canadensis can be recommended as a bio-indicator for radioactively contaminated aquatic ecosystems.


Anti-inflammatory and peripheral analgesic activity of esculetin in vivo.
Esculetin determined a reduction in oedema and granulocyte infiltration in the Croton oil ear test in vivo. The drug was able to inhibit Acethylcholine-writhing test and showed a LD50 of 1450 mg/kg i.p. and greater than 2000 mg/kg by mouth. In our experimental conditions, esculetin has an anti-inflammatory and analgesic effect.


Periodic local MP2 method for the study of electronic correlation in crystals: Theory and preliminary applications.
A computational technique for solving the MP2 equations for periodic systems using a local-correlation approach and implemented in the CRYSCOR code is presented. The Hartree-Fock solution provided by the CRYSTAL program is used as a reference. The motivations for the implementation of the new code are discussed, and the techniques adopted are briefly recalled. With respect to the original formulation (Pisani et al., J Chem Phys 2005, 122, 094113), many new features have been introduced in CRYSCOR to improve its efficiency and robustness. In particular, an adaptation of the density fitting scheme to translationally periodic systems is described, based on Fourier transformation techniques. Three examples of application are provided, concerning the CO(2) crystal, proton transfer in ice XI, and the adsorption of methane on MgO (001). The results obtained with the periodic LMP2 method for these systems appear more reliable than the ones obtained using density functional theory.


Bibliometric analysis on research trends for contribution of photodynamic therapy in periodontitis.
The objective of this bibliometric analysis was to ascertain the research trend regarding the application of photodynamic therapy as a treatment modality for periodontal disease. An online search was administered using the Scopus database to retrieve all the relevant research literature published from 2003 till 26th Dec 2022. After applying the inclusion criteria articles pertinent to the topic were manually selected. Data was saved as CSV. Data was read using VOSviewer software and further analysis was performed using Microsoft excel. From a total of 545 articles, 117 scientific papers relevant to the field were evaluated. The keen interest of researchers was identified by an increase in the number of publications over the course of time, with the highest citations n = 827 attained during the year 2009. Brazil, India, and USA made significant contribution by publishing highest number of papers. Organizations from the USA produced the highest publications which attained high citations. Author Sculean A. published the highest number of papers. Journal of periodontology was the leading journal, by publishing highest number of papers (n = 15), followed by Journal of Clinical Periodontology. This bibliometric analysis provided detailed information regarding the total number of publications from 2003 to 2022 and the number of citations attained. Brazil has been identified as the leading country, whilst all the leading organizations which contributed significantly, were from USA. The Journal of Periodontology published the highest number of papers which had been highly cited. Sculean A, affiliated with University of Bern, Switzerland published the highest number of papers.


Immunization with a suicidal DNA vaccine expressing the E glycoprotein protects ducklings against duck Tembusu virus.
Duck Tembusu virus (DTMUV), a pathogenic flavivirus, emerged in China since 2010 and causing huge economic loss in the Chinese poultry industry. Although several vaccines have been reported to control DTMUV disease, few effective vaccines are available and new outbreaks were continuously reported. Thus, it is urgently to develop a new effective vaccine for prevention of this disease. In this study, a suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon and DTMUV E glycoprotein gene was constructed and the efficacy of this new vaccine was assessed according to humoral and cell-mediated immune responses as well as protection against the DTMUV challenge in ducklings. Our results showed that the recombinant SFV replicon highly expressed E glycoprotein in DEF cells. After intramuscular injection of this new DNA vaccine in ducklings, robust humoral and cellular immune responses were observed in all immunized ducklings. Moreover, all ducklings were protected against challenge with the virulent DTMUV AH-F10 strain. In conclusion, we demonstrate that this suicidal DNA vaccine is a promising candidate facilitating the prevention of DTMUV infection.


Relevance of surgery after embolization of gastrointestinal and abdominal hemorrhage.
Gastrointestinal and abdominal bleeding can lead to life-threatening situations. Embolization is considered a feasible and safe treatment option. The relevance of surgery has thus diminished in the past. The aim of the present study was to evaluate the role of surgery in the management of patients after embolization. We performed a retrospective single-center analysis of outcomes after transarterial embolization of acute abdominal and gastrointestinal hemorrhage between January 2009 and December 2012 at the Sisters of Charity Hospital, Linz. Patients were divided into three groups, as follows: upper gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), and abdominal hemorrhage. Fifty-four patients with 55 bleeding events were included. The bleeding source could be localized angiographically in 80 %, and the primary clinical success rate of embolization was 81.8 % (45/55 cases). Early recurrent bleeding (<30 days) occurred in 18.2 % (10/55) of the patients, and delayed recurrent hemorrhage (>30 days) developed in 3.6 % (2/55). The mean follow-up was 8.4 months, and data were available for 85.2 % (46/54) of the patients. Surgery after embolization was required in 20.4 % of these patients (11/54). Failure to localize the bleeding site was identified as predictive of recurrent bleeding (p = 0.009). More than one embolization effort increased the risk of complications (p = 0.02) and rebleeding (p = 0.07). Surgery still has an important role after embolization in patients with gastrointestinal and abdominal hemorrhage. One of five patients required surgery in cases of early and delayed rebleeding or because of ischemic complications (2/55 both had ischemic damage of the gallbladder) and bleeding consequences.


Chronic alcohol exposure increases ganglia endogenous morphine levels.
We have previously demonstrated that alcohol has the ability to release low levels of endogenously expressed, chemically authentic, morphine from neural tissues. Presently, we demonstrate that chronic exposure of Mytilus edulis pedal ganglia tissues maintained in organotypic culture to very concentrations of 1 mM and 10 mM ethanol induces a time dependent increase in both endogenous morphine and dopamine (DA) levels. Chronic incubation of M. edulis pedal ganglia with 3 concentrations of DA resulted in statistically significant elevations of cellular morphine levels, thereby confirming previous studies from our laboratory establishing DA as an essential precursor in the morphine biosynthetic pathway. By understanding multiple debilitating effects of alcohol on "morphinergic" signaling, we may understand the ravages of neural processes associated with alcohol abuse and how its treatment may be made more effective.


Effects of ceria nanoparticles and CeCl3 on growth, physiological and biochemical parameters of corn (Zea mays) plants grown in soil.
The release of toxic ions from metal-based nanoparticles (NPs) may play an important role in biological effects of NPs. In this life cycle study, physiological and biochemical responses of soil-grown corn (Zea mays) plants exposed to ceria NPs and its ionic counterparts Ce3+ ions at 0, 25, 75 and 225 mg Ce/kg were investigated. Both treatments tended to reduce the fresh weight and height of the plants at 28 days after sowing (DAS), and delay silk appearance and finally decrease fruit weight at harvest. Uptake and distribution of some mineral nutrients, Ca, P, Fe, B, Zn and Mn in the plants were disturbed. None of the treatments significantly affected activities of antioxidant enzymes and MDA contents in the roots and leaves at 28 DAS. At 90 DAS, ceria NPs and Ce3+ ions disturbed the homeostasis of antioxidative systems in the plants, Ce3+ ions at all concentrations provoked significant oxidative damage in the roots and significantly increased MDA levels as compare to the control. The results indicate that the effects of ceria NPs and Ce3+ ions on corn plants varied with different growth stages and ceria NPs had similar but less severe impacts than Ce3+ ions. Speciation analysis revealed there was mutual transformation between CeO2 and Ce3+ in the soil-plant system. It is speculated that Ce3+ ions play a key role in toxicity. To the authors' knowledge, this is the first report of a life cycle study on comparative toxicity of CeO2 NPs and Ce3+ ions on corn plants.


Liver epithelial cell migration induced by epidermal growth factor or transforming growth factor alpha is associated with changes in the gene expression of secreted proteins.
Rat liver epithelial cells are induced to migrate by epidermal growth factor (EGF) or transforming growth factor alpha (TGF-alpha) in serum-free medium supplemented with insulin. Immunohistological staining of the migration tracks containing laminin and fibronectin has allowed a quantitative analysis of the process. The growth factor-induced migration is relatively slow, but very efficient. Between 24 and 48 h after exposure to EGF (or TGF-alpha), 50 to 70% of the cells have migrated away from their site of initial attachment and spreading. This delayed effect of the interaction of the receptor with its ligands is associated with changes in gene expression, but is not associated with a stimulation of cell proliferation. In serum-free medium supplemented with insulin, the cells secrete six major proteins, as revealed by SDS-polyacrylamide gel electrophoresis. The media of cultures supplemented with insulin plus EGF (or TGF-alpha) contain in addition two new proteins and an increased amount of fibronectin. One secreted protein is synthesized in significantly reduced amounts. The most conspicuously EGF-induced protein (EIP-1; Mr 47,000) is detected within 2 h, depends on the continued presence of the growth factor, and has not been detected as bound to the substratum. The stringent regulation of EIP-1 suggests that this gene product might participate in the modulation of the changes induced by the growth factor. The system is being used for the further analysis of the regulation of gene expression by EGF and of the migration of normal and neoplastically transformed epithelial cells.


Schwann Cell-derived exosomes promote bone regeneration and repair by enhancing the biological activity of porous Ti6Al4V scaffolds.
Implants made of porous titanium alloy and fabricated by 3D printing are increasingly used in clinical research. However, porous titanium alloys do not integrate very well with surrounding bone tissue, and bone ingrowth into the implants is not substantial. Schwann cells (SCs) and SC-derived exosomes can effectively promote nerve regeneration, but their role in bone tissue regeneration and repair has not been studied. Therefore, we added SC-derived exosomes to bone marrow stromal cell (BMSC) cultures and observed their effect on BMSCs in vitro; then, we combined exosomes with porous Ti6Al4V scaffolds and observed their effects on bone regeneration and repair in vivo. We found that SC-derived exosomes could promote the migration, proliferation and differentiation of BMSCs and that combining exosomes with porous titanium alloy can effectively improve the efficacy of titanium alloy scaffolds in bone repair. The combination of exosomes and porous Ti6Al4V implants may constitute a new therapeutic strategy for treating bone defects.


Detection of bacteria in stored red cell products using a culture-based bacterial detection system.
The Pall eBDS uses oxygen consumption as a surrogate marker for bacterial detection in platelet (PLT) products. This article describes the evaluation of eBDS to detect bacterial contamination in inoculated fresh and stored leukoreduced red cell (RBC) units. Field studies were conducted at three sites to establish eBDS pouch incubation time and the pass/fail threshold. RBC units were inoculated with each of 12 bacterial species known to cause sepsis at target inocula of either 1 to 15 or 100 colony-forming units (CFUs) per mL. Units were mixed and stored at 2 to 6 degrees C. Samples were taken for culture and eBDS testing weekly from 0 hour to 42 days and incubated for 35 degrees C for 24 to 30, 48, and 72 hours, followed by measurement of percent oxygen content. The studies showed growth of five bacterial species (including Yersinia enterocolitica) in RBC units, while seven bacterial species showed no growth or autosterilized. A pass/fail oxygen threshold of 14.4 percent was determined based on results from noninoculated controls (n = 633) and from inoculated samples (n = 884) after 48 hours of incubation. Detection was 100 percent at all sampling times during refrigerated storage with both 48 and 72 hours of pouch incubation. With incubation of eBDS pouches for 48 and 72 hours, 100 percent detection was obtained in 884 samples with bacterial levels of at least 1 CFU per mL, and no false-positive samples were obtained. Based on the bacterial growth patterns, RBC units may be sampled 1 to 3 days after collection for optimal efficacy and read after 48 to 72 hours of incubation of the eBDS sample pouches at 35 degrees C. The Pall eBDS is suited for detection of typical bacterial contaminants in fresh and stored RBCs.


Temporomandibular joint anterior disc displacement with reduction in a young population: Prevalence and risk indicators.
Temporomandibular joint (TMJ) anterior disc displacements with reduction (ADDR) are commonly found in the young population and often found to be associated with biomechanical and anatomical factors. Until now, most knowledge on ADDR among children and adolescents comes from studies performed on Caucasian subjects. To assess the clinically determined prevalence rates of ADDR among the young Indonesian population and to evaluate its risk indicators. In this cross-sectional study, 1562 pupils and students of 7-21 years old completed a questionnaire and underwent a clinical examination. The prevalence rates of ADDR were 7.0% among children (7-12 years), 14.4% among adolescents (13-18 years), and 12.3% among young adults (19-21 years). Logistic regression analyses revealed that increasing age and lip biting were associated with ADDR in children, whereas pen biting was associated with ADDR in the adolescent population. None of the included factors were found to be associated with ADDR in the young adult population. The present findings indicate that prevalence of ADDR increases with age, with a peak during the years of adolescence. Biomechanical factors seem to play a significant role in ADDR development.


A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma.
Melanomas frequently harbor activating NRAS mutations. However, limited advance has been made in developing targeted therapy options for patients with NRAS mutant melanoma. MEK inhibitors (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacologic and molecular approaches. Combined PDPK1 inhibitors (PDPK1i) with MEKi suppressed NRAS mutant xenograft growth and induced gasdermin E-associated pyroptosis. In an immune-competent allograft model, PDPK1i+MEKi increased the ratio of intratumoral CD8+ T cells, delayed tumor growth, and prolonged survival; the combination treatment was less effective against tumors in immune-deficient mice. These data suggest PDPK1i+MEKi as an efficient immunostimulatory strategy against NRAS mutant melanoma. Targeting PDPK1 stimulates antitumor immunity and sensitizes NRAS mutant melanoma to MEK inhibition, providing rationale for the clinical development of a combinatorial approach for treating patients with melanoma.


The prognostic value of optic nerve sheath diameter in patients with subarachnoid hemorrhage.
We evaluated the role of optic nerve sheath diameter (ONSD) using brain computed tomography (CT) in predicting neurological outcomes of patients with subarachnoid hemorrhage (SAH). This was a retrospective, multicenter, observational study of adult patients with SAH admitted between January 2012 and June 2017. Initial brain CT was performed within 12 h from onset of SAH, and follow-up brain CT was performed within 24 h from treatment of a ruptured aneurysm. Primary outcome was neurological status at 6-month follow-up assessed with the Glasgow Outcome Scale (GOS, 1 to 5). Among 223 SAH patients, 202 (90.6%) survived until discharge. Of these survivors, 186 (83.4%) manifested favorable neurological outcomes (GOS of 3, 4, or 5). In this study, the ONSDs in the group of patients with poor neurological outcome were significantly greater than those in the favorable neurological outcome group (all p < 0.01). Intracranial pressure (ICP) was monitored in 21 (9.4%) patients during the follow-up CT. A linear correlation existed between the average ONSD and ICP in simple correlation analysis (r = 0.525, p = 0.036). Analysis of the receiver operating characteristic curve for prediction of poor neurological outcome showed that ONSD had considerable predictive value (C-statistics, 0.735 to 0.812). In addition, the performance of a composite of Hunt and Hess grade and ONSD was increasingly associated with poor neurological outcomes than the use of each marker alone. ONSD measured with CT may be used in combination with clinical grading scales to improve prognostic accuracy in SAH patients.


Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney.
Nephrotoxicity is a dose limiting side effect of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection. The mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically toxic to the proximal convoluted tubules and proximal tubular mitochondria are the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of reactive oxygen species and cellular damage is reported to occur after the antioxidants are depleted. The purpose of the study is to investigate the alterations in cellular antioxidant system in tenofovir induced renal damage using a rat model. Chronic tenofovir administration to adult Wistar rats resulted in proximal tubular damage (as evidenced by light microscopy), proximal tubular dysfunction (as shown by Fanconi syndrome and tubular proteinuria), and extensive proximal tubular mitochondrial injury (as revealed by electron microscopy). A 50% increase in protein carbonyl content was observed in the kidneys of TDF treated rats as compared with the control. Reduced glutathione was decreased by 50%. The activity of superoxide dismutase was decreased by 57%, glutathione peroxidase by 45%, and glutathione reductase by 150% as compared with control. Carbonic Anhydrase activity was decreased by 45% in the TDF treated rat kidneys as compared with control. Succinate dehydrogenase activity, an indicator of mitochondrial activity was decreased by 29% in the TDF treated rat kidneys as compared with controls, suggesting mitochondrial dysfunction. Tenofovir- induced mitochondrial damage and increased oxidative stress in the rat kidneys may be due to depletion of the antioxidant system particularly, the glutathione dependent system and MnSOD.


Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.
Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p < 0.001, respectively). Plasma glucose tended to increase (p = 0.070) and hemoglobin A1c significantly increased (p < 0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.


Paul Klee's illness-a series of historical and clinical vignettes, part II.
Viewing and analyzing fine art from a medical perspective increases our appreciation of the artist's suffering and teaches an important lesson of the human aspects of medicine. Paul Klee (1879-1940), one of the most influential artists of the 20th century, died at the age of 60 from complications of systemic sclerosis (scleroderma). In this second, in a series of clinical vignettes, I discuss the musculoskeletal manifestations of systemic sclerosis and how they may have influenced the life and art of Paul Klee.


Synthesis and transformations of di-endo-3-aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic acid derivatives.
all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all-endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of b-amino ester 4 resulted in tricyclic pyrimidinones 15 and 16. The structures, stereochemistry and relative configurations of the synthesized compounds were determined by IR and NMR.


Exolaryngoscopy: a new technique for laryngeal surgery.
The aim of this study is to assess the use of a telescope with a high definition endoscopic video system as an alternative to the operating microscope in endoscopic laryngeal surgery. The system is economic, and allows optimal vision and improved surgeon comfort and ease. In exolaryngoscopy, the optic vitom is positioned in place of the microscope. An extracorporeal optical system (exoscope) is positioned 25 cm from the surgical field. Under exoscopic control, it is possible to use the same series of instruments using a long handle through the laryngoscope. The CO2 laser may also be used by fixing it coaxially to the optical system, and it is possible to use a classic set of microinstruments for phonosurgery. Endoscopic study with auto-fluorescence (NBI; narrow band imaging) can be easily used to visualize both precancerous and cancerous lesions. We treated 12 patients with benign and malign pathologies of the vocal cords; in all cases, the predicted result was reached, and the optic vitom showed its potential advantages in ease and comfort of the surgeon.


Effect of intra-articular hyaluronan on pressure-flow relation across synovium in anaesthetized rabbits.
1. Hyaluronan is the major polysaccharide of synovial fluid, responsible for its high viscosity. The effect of hyaluronan on fluid transport across the synovial lining of the joint was investigated. Rate of fluid absorption from the joint cavity (Qs) was measured at intra-articular pressures (Pj) of up to 24 cmH2O in knees of anaesthetized rabbits, in the presence or absence of hyaluronan in intra-articular infusates. 2. Viscometry studies in vitro showed that the commercial hyaluronan used had a molecular weight of 549,000-774,000, a radius of gyration of 48-99 nm and a critical concentration for molecular overlap of 1.3 g l-1. 3. With intra-articular Krebs solution (control) or subnormal, subcritical concentrations of hyaluronan (0.5 g l-1), flow increased with pressure. Hyaluronan reduced the fluid escape rate by reducing slope dQs/dPj by 32-64% relative to Krebs solution. 4. At normal to high hyaluronan concentrations (3-6 g l-1) and low pressures, hyaluronan again reduced slope dQs/dPj, by 39-64%. The reduction in slope was slight, however, when compared with the reduction in bulk fluidity (1/relative viscosity). Fluidity at high shear rates was reduced to 6% of control values by 6 g l-1 hyaluronan. The effect on slope did not correlate significantly with the effect on fluidity. 5. At pressures above approximately 12 cmH2O, 3-6 g l-1 hyaluronan altered the shape of the pressure-flow relation: a flow plateau developed. In some joints raising pressure even reduced trans-synovial flow slightly. The pressure required to drive unit trans-synovial flow (an index of outflow resistance) increased 2.5-fold between 5 and 25 cmH2O in the presence of hyaluronan. By contrast, in the absence of hyaluronan the outflow resistance fell as pressure was raised. 6. It is suggested that the increasing resistance to flow in the presence of hyaluronan may be caused by partial molecular sieving of hyaluronan by the small porosities of the synovial interstitial matrix, leading to accumulation of a resistive filter cake of hyaluronan chains at the tissue-cavity interface. Since hyaluronan impedes fluid escape when pressure is raised, it may serve to preserve synovial fluid volume in vivo, e.g. during sustained joint flexion.


Higher levels of brain derived neurotrophic factor but similar nerve growth factor in human milk in women with preeclampsia.
Children born to mothers with preeclampsia have consistently been suggested to be at risk for cognitive and behavioral disorders in later life. Breastfeeding is said to be associated with better neurodevelopment outcomes. Our earlier studies indicated higher levels of docosahexaenoic acid (DHA) in human milk in women with preeclampsia. DHA is known to regulate the expression of neurotrophins and together they play a vital role in neurodevelopment and cognitive performance. The present study examines the levels of maternal plasma and milk neurotrophins [(nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)] in women with preeclampsia and compares them with normotensive women who served as controls. Singleton pregnant women diagnosed with preeclampsia (n=72) and controls (n=102) were recruited for this study from Bharati Hospital, Pune. Plasma and milk samples were analyzed for NGF and BDNF levels using the Emax Immuno Assay System using promega kits. Maternal plasma NGF and BDNF levels were lower (p<0.01 for both) in women with preeclampsia as compared to the control women. Milk NGF levels were similar while milk BDNF levels were higher (p<0.05) in the preeclampsia group as compared to controls. Plasma NGF levels were positively correlated with milk NGF levels in the control group. Our results indicate the differential regulation of milk NGF and BDNF levels in women with preeclampsia. The present study suggests a role for both NGF and BDNF in human milk for postnatal brain development. Further studies need to examine the associations of DHA and BDNF in human milk with cognition at later ages.


Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma.
The Wnt gene family members are known to participate regulating various normal and pathological processes including tumorigenesis. However, the association between Wnt ligands gene family and prognosis in hepatocellular carcinoma has not been systematically studied. Therefore, we evaluated the role of Wnt ligands gene family in hepatocellular carcinoma using publicly available data from The Cancer Genome Atlas (TCGA). Clinical information and RNA-Seq mRNA expression data were derived from TCGA hepatocellular carcinoma cohort. Differences in overall survival (OS) and disease-free survival (DFS) between increased and decreased expression groups (defined by X-tile analyses) of Wnt ligands gene family were compared using Kaplan-Meier method and Cox regression model, with p-values calculated via log-rank test. Gene Set Enrichment Analysis (GSEA) was performed. Multivariate analysis adjusted for patient age, sex, BMI, tumor grade, and TMN stage revealed that Wnt1, Wnt3 and Wnt5B expressions were independent prognostic factors for OS and DFS (OS: HR = 0.58, P = 0.006; HR = 0.65, P = 0.03; HR = 0.56, P = 0.023, respectively; DFS: HR = 0.52, P < 0.001; HR = 1.93, P = 0.003; HR = 0.59, P = 0.011, respectively). Furthermore, expression of Wnt1 and Wnt5B was significantly associated with TMN stage (P = 0.02 and P = 0.03 for OS; P = 0.02 and P = 0.02 for DFS). GSEA showed that nucleotide excision repair was differentially enriched in Wnt1 low expression phenotype and aminoacyl trna biosynthesis and basal transcription factors were differentially enriched in Wnt5B low expression phenotype. Our results identified associations of several Wnt ligands with prognosis of HCC patients, indicating that these genes could serve as prognostic biomarkers of HCC.


Rational design of a new series of mixed anti-HIV pronucleotides.
MonoSATE aryl phosphotriesters of AZT are able to deliver intracellularly the corresponding 5'-mononucleotide. This process requires activation by an esterase followed by a phosphodiesterase. This finding opens the way to the design of new pronucleotide series.


Serological evidence of Paracoccidioides brasiliensis infection in chickens from Paraná and Mato Grosso do Sul States, Brazil.
The objective of this study was to detect antibodies against Paracoccidioides brasiliensis in free-range and caged chickens Gallus domesticus. Initially, the humoral immune response of two chickens immunized with P. brasiliensis was evaluated. Both animals showed the production of antibodies to gp43, the major P. brasiliensis antigen. The seroepidemiological survey was conducted in chickens from the Pantanal region in Mato Grosso do Sul State (free-range n = 40) and from northern region of Paraná State (free-range n = 100, caged n = 43). The serum samples were analyzed by indirect ELISA using gp43 as antigen. The positivity observed in free-range chickens from Mato Grosso do Sul (55%) was significantly higher (P = 0.0001) than in free-range chickens from Paraná State (16%). In contrast to the free-range chickens, no positivity was observed in the caged chickens (P = 0.003). This is the first report showing serological evidence of P. brasiliensis infection in chickens. The results suggest that free-range chickens are more frequently infected by P. brasiliensis, probably due to the constant contact with soil than caged chickens and could be useful as epidemiological markers of paracoccidioidomycosis.


Plasma and synovial fluid programmed cell death 5 (PDCD5) levels are inversely associated with TNF-α and disease activity in patients with rheumatoid arthritis.
Programmed cell death 5 (PDCD5), a novel apoptotic regulatory gene, has been reported to be associated with rheumatoid arthritis (RA) and osteoarthritis (OA), which can regulate the apoptosis of synoviocytes and chondrocytes cultured in vitro. To study expression characteristic of PDCD5 in plasma and synovial fluid of RA patients, and analyze its correlation with tumor necrosis factor alpha (TNF-α) and disease activity in RA. A total of 135 subjects were recruited into this study (44 RA patients, 46 OA patients and 45 healthy controls). PDCD5 and TNF-α concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. Plasma and synovial fluid PDCD5 concentrations were significantly elevated in RA patients. Pearson correlation analysis indicated that plasma and synovial fluid PDCD5 levels were inversely correlated with TNF-α. Moreover, plasma PDCD5 levels were also inversely correlated with C-reactive protein and erythrocyte sedimentation rate. Plasma and synovial fluid PDCD5 could be useful for monitoring the activity and progression of RA, and its abnormal expression and dysfunction may be correlated to TNF-α in RA patients.


Effect of dopamine antagonism on carotid chemoreceptor interspike intervals.
As a means of examining the role of dopamine in chemotransduction, we examined the spike interval pattern from single carotid body chemoreceptors before and following dopamine antagonism. Before dopamine antagonism, chemoreceptor joint interval variability was less than the variability of the same spike interval series placed in shuffled order. This lower variability was abolished by dopamine antagonism with haloperidol. These data suggest that dopamine release reduces chemoreceptor interspike variability in vivo and that endogenous, local dopamine release is related to the activity level of a single chemoreceptor afferent.


Macrophage polarization by potential nutraceutical compounds: A strategic approach to counteract inflammation in atherosclerosis.
Chronic inflammation represents a main event in the onset and progression of atherosclerosis and is closely associated with oxidative stress in a sort of vicious circle that amplifies and sustains all stages of the disease. Key players of atherosclerosis are monocytes/macrophages. According to their pro- or anti-inflammatory phenotype and biological functions, lesional macrophages can release various mediators and enzymes, which in turn contribute to plaque progression and destabilization or, alternatively, lead to its resolution. Among the factors connected to atherosclerotic disease, lipid species carried by low density lipoproteins and pro-oxidant stimuli strongly promote inflammatory events in the vasculature, also by modulating the macrophage phenotyping. Therapies specifically aimed to balance macrophage inflammatory state are increasingly considered as powerful tools to counteract plaque formation and destabilization. In this connection, several molecules of natural origin have been recognized to be active mediators of diverse metabolic and signaling pathways regulating lipid homeostasis, redox state, and inflammation; they are, thus, considered as promising candidates to modulate macrophage responsiveness to pro-atherogenic stimuli. The current knowledge of the capability of nutraceuticals to target macrophage polarization and to counteract atherosclerotic lesion progression, based mainly on in vitro investigation, is summarized in the present review.


Determinants of surgical repair of patent ductus arteriosus in low-birth-weight infants.
To identify risk factors related to the failure of indomethacin therapy and the need for surgical repair in patent ductus arteriosus (PDA) in extremely low-birth-weight (<1000 g) infants (ELBWI). Study subjects were 36 ELBWI with PDA born at a single tertiary perinatal center. They were classified into those who required surgery due to failure of indomethacin treatment (surgical group, n = 21) and those with effective indomethacin treatment (non-surgical group, n = 15). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for the relationship between selected risk factors and surgical treatment of PDA were calculated. Gestational age of <28 weeks and diameter of PDA of 2 mm or more were independent and significant determinants of the need for surgical repair of PDA (adjusted ORs [95% CIs] = 9.91 [1.16-84.48] and 24.80 [2.72-225.74], respectively). The need for surgical repair of PDA did not correlate with sex, birth weight, 1-min Apgar score, left atrium diameter/aortic diameter (LA/Ao), left ventricular internal dimension at end-diastole, prophylaxes with indomethacin, and total dosage of indomethacin. Gestational age at birth of <28 weeks and diameter of PDA of 2 mm or more are determinants of failure of indomethacin treatment for PDA and the need for surgical repair.


Anesthesia in head and neck surgery. Head and neck cancer surgery and maxillofacial trauma.
Safe anesthetic management of head and neck surgery and maxillofacial trauma depends on an accurate identification of ancillary problems, precise intraoperative monitoring, and treatment. Protocols facilitate thorough management, and a discussion is provided.


Planning area-specific prevention and intervention programs for HIV using spatial regression analysis.
The study was conducted to inform area-based prevention intervention programs and plan resource allocation to reduce new infections in the District of Columbia (DC), United States of America. The analysis used spatial regression to evaluate the spatial heterogeneity of the new HIV rate and its association with sexually transmitted infection repeaters (STIREPs) and socio-economic as well as demographic characteristics. The HIV and STIREP data were obtained from the DC Department of Health surveillance data (2010-2016). Other covariates were obtained from the American Community Survey, 2016. Ordinary least squares (OLS) and geographically weighted regression (GWR) were used to compare global and local relationships. GWR-computed robust results were compared with other spatial regression methods such as spatial lag or spatial error methods. For the OLS model, age, high school dropouts (NHSD), and the black population had an association with new HIV diagnoses (HIVDVi). The results from the GWR model demonstrate spatial variations of association of STIREPs; mean age of each block group; and percentage of female population, NHSD, unemployment, and poverty with HIVDVi. Akaike information criterion (AICc) value for the global model was 2770.99, and R2 was 0.54 (54%). The R2 and AICc of the GWR model was 0.81 (81%) and 2580.84, respectively, where the latter showed a 0.27 (27%) increase in R2 and a decreased AICc. These results will assist in planning HIV prevention and intervention strategies. These results will also be used for targeted testing, planning pre-exposure prophylaxis, and access to health care. The results will help plan resource allocation to community-based providers for prevention intervention programs and fund public health programs such as condom distribution, mobile vans, and youth-based sex education.


Use of a larynyngeal mask airway during aortic valve replacement.
We report the elective use of a laryngeal mask airway during cardiac surgery for congenital tracheal stenosis. A 53-year-old woman with severe aortic valve stenosis was scheduled for aortic valve replacement. During anesthesia induction, the anesthesiologists attempted conventional intubation but failed. Fiberoptic tracheal examination and computed tomography showed a tracheal stenosis with 5 mm minimal diameter. A laryngeal mask airway was used at the patient's rescheduled surgery. The laryngeal mask airway use did not lead any surgical complication. We concluded that the laryngeal mask airway may be considered as an alternative to conventional intubation in patients with tracheal stenosis.


Nutritional pharmacology in surgical patients.
The use of pharmaconutrition for supportive care of surgical patients is now well established, but the field is still in its infancy. Complex pharmaconutrient formulas containing arginine, glutamine, and n-3 fatty acids have been proven to shorten hospital stay, decrease the incidence of infection, and reduce hospital costs in selected groups of patients. The effects are greatest in those patients with severe trauma including burn injury, those undergoing major surgical procedures, especially when malnourished, and those who are critically ill ICU patients including patients with existing infection. The complex interaction of pharmaconutrients and other pharmacologic agents are just now beginning to be investigated.


[The determination of the level of the external osteotomy line in Le Fort I interventions for pure maxillary advancement].
Therapy of severe malocclusions needs a cooperation between orthodontist and maxillo-facial surgeon. The aim of this study is to evaluate how the ortho-surgical team can get a common base of programmation to transfer on split-casts osteotomic simulation reaching a more exact surgical result. In this paper were considered patients operated by orthognathic surgery from January 1994 to June 1997 have been studied. Patients were operated in the Institute in which authors work. Patients included were 120, 65 female and 55 male between 20 and 42 (mean 31). Patients were operated, for the most part, by combined operation at maxilla and mandible. RECORDINGS: The mean of values noticed was calculated adding all values and dividing for the number of values. The mean calculated is 33 mm (DS 2,22) of distance from canine cusp and 29 mm (DS 2,19) from mesio-vestibular cusp of the first upper molar. This study demonstrates that it is possible, with a statistically significant precision, to transfer osteotomic reference lines from clinical practice to a planning more pertinent to surgical performance. In this study we tried to standardize a value to increase precision of surgery, transferring easily feasible surgical measurements to split-casts.


A quantitative EEG method for detecting post clamp changes during carotid endarterectomy.
To apply univariate and multivariate analyses of EEG spectral features in order to detect subtle post-clamp changes during carotid endarterectomy, and to devise a data-driven, multivariate classification method for rapid, real-time detection of small post-clamp EEG changes. We used intraoperative EEG records of 27 patients who underwent carotid endarterectomy (CEA) and did not undergo a shunt per surgeon's and technologist's visual inspection of the electro-encephalogram (EEG). Furthermore, these records could not be flagged with r-sBSI (revised spatial brain symmetry index) or r-tBSI (revised temporal brain symmetry index) qEEG (quantitative EEG) metrics. Spectral energies of 10 s EEG snippets were recorded at 5 min intervals from 10 min pre-clamp to 20 min post-clamp. Using receiver operating characteristic curves, the power of standard EEG spectral bands in detection of post-clamp changes was determined. Next, we employed Fisher Linear Discriminant Analysis for classifier-guided multivariate feature selection and classification. In univariate analysis, delta waves in non-frontal areas, irrespective of the laterality of the affected hemisphere, were found to be generally more powerful indicators of clamp-induced EEG changes. In multivariate analysis, cross-validation results for Fisher LDA produced subject-independent equal error rates as low as 32% when separating post-clamp signals from pre-clamp controls. Within our subject group, the intricate clamp-induced EEG signatures were predominantly anterior, bilateral, and had a strong delta rhythm presence. The overall post-clamp saliencies, both in univariate and multivariate analyses, were time-dependent. By applying automatic data-driven feature extraction and classification to short EEG records, it is possible to construct subject-independent computational models that can detect subtle post clamp changes possibly caused by small perturbations in cerebral blood flow. These subtle changes are missed by visual inspection of the EEG and by other quantitative EEG techniques such as r-sBSI and r-tBSI. Within our subject group, the intricate post-clamp EEG signatures were predominantly anterior, bilateral, and had a strong delta rhythm presence.


6S RNA Mimics B-Form DNA to Regulate Escherichia coli RNA Polymerase.
Noncoding RNAs (ncRNAs) regulate gene expression in all organisms. Bacterial 6S RNAs globally regulate transcription by binding RNA polymerase (RNAP) holoenzyme and competing with promoter DNA. Escherichia coli (Eco) 6S RNA interacts specifically with the housekeeping σ70-holoenzyme (Eσ70) and plays a key role in the transcriptional reprogramming upon shifts between exponential and stationary phase. Inhibition is relieved upon 6S RNA-templated RNA synthesis. We report here the 3.8 Å resolution structure of a complex between 6S RNA and Eσ70 determined by single-particle cryo-electron microscopy and validation of the structure using footprinting and crosslinking approaches. Duplex RNA segments have A-form C3' endo sugar puckers but widened major groove widths, giving the RNA an overall architecture that mimics B-form promoter DNA. Our results help explain the specificity of Eco 6S RNA for Eσ70 and show how an ncRNA can mimic B-form DNA to directly regulate transcription by the DNA-dependent RNAP.


Role of multiple risk factors in mental disorders diagnosed in middle-aged women: A population-based follow-up study.
The aims of the study were 1). to investigate the association between the potential risk factors including socio-demographic, lifestyle and DNA methylation and mental disorders in middle-aged women from a large population-based follow-up study, and 2). to estimate the risk score by combining the potential risk factors to examine the mental disorder's incidence. A total of 6461 women, aged 50-65 years, were included in the study. After a median follow-up of 17 years, 2026 (31%) women were diagnosed with mental disorders. The association between these factors and the risk of mental disorders was analyzed using Cox regression models. Harrell's concordance index (C-index) was used to quantify models' predictive performance for future mental disorders. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. We found that smoking (HR = 1.38, 95% CI: 1.24-1.54), less physical activity (HR = 1.33, 95% CI: 1.10-1.60), being single (HR = 1.16, 95% CI: 1.04-1.29) and unemployment (HR = 1.50, 95% CI: 1.33-1.70) were independently associated with an increased risk of overall mental disorders. Risk score models combining all these observed factors showed an increased risk, but the prediction ability was low, except for the risk of alcohol use disorders (AUD) and drug use disorders (DUD) (C-index = 0.8). Finally, women who developed MDD/anxiety during follow-up had significantly higher global DNA methylation at baseline than women who did not develop MDD/anxiety (p = 0.005). In conclusion, our results indicate that the studied risk factors were associated with mental disorders in a type-specific manner. The predictive model showed that smoking, alcohol consumption, education and physical activity may predict future AUD/DUD. Global DNA methylation may be a potential risk factor for MDD/anxiety incidence.


Alteration of the substrate specificity of benzoylformate decarboxylase from Pseudomonas putida by directed evolution.
Alteration of the substrate specificity of thiamin diphosphate (ThDP)-dependent benzoylformate decarboxylase (BFD) by error-prone PCR is described. Two mutant enzymes, L476Q and M365L-L461S, were identified that accept ortho-substituted benzaldehyde derivatives as donor substrates, which leads to the formation of 2-hydroxy ketones. Both variants, L476Q and M365L-L461S, selectively catalyze the formation of enantiopure (S)-2-hydroxy-1-(2-methylphenyl)propan-1-one with excellent yields, a reaction which is only poorly catalyzed by the wild-type enzyme. Different ortho-substituted benzaldehyde derivatives, such as 2-chloro-, 2-methoxy-, or 2-bromobenzaldehyde are accepted as donor substrates by both BFD variants as well and conversion with acetaldehyde resulted in the corresponding (S)-2-hydroxy-1-phenylpropan-1-one derivatives. As deduced from modeling studies based on the 3D structure of wild-type BFD, reduction of the side chain size at position L461 probably results in an enlarged substrate binding site and facilitates the initial binding of ortho-substituted benzaldehyde derivatives to the cofactor ThDP.


Organization and interviral homologies of the coat protein gene of white clover mosaic virus.
The sequence of 1612 nucleotides of the 3'-terminal region of white clover mosaic virus (WCIMV) has been determined from cDNA clones. The viral sense RNA contains four open reading frames of Mr 20,684, Mr 7219, Mr 12,989, and at least Mr 17,000. The latter begins 5' to the sequence determined. The amino acid sequence of the open reading frame encoding the 20,684 polypeptide shows marked homology to the coat proteins of three other potexviruses. The putative coat protein gene was subcloned in a T7 transcription plasmid and RNAs produced by in vitro transcription were translated in the rabbit reticulocyte lysate system. The polypeptide products comigrated on SDS-polyacrylamide gels with one of those synthesized by the in vitro translation of viral RNA, and were immunoprecipitable with antiserum raised against WCIMV, confirming the location of the coat protein gene.


The effect of ethambutol on mycobacterial cell wall permeability to hydrophobic compounds.
Ethambutol (EMB), the first line drug in the treatment of tuberculosis, is an inhibitor of the biosynthesis of the cell wall compound - arabinogalactan. It was found that EMB at sub-inhibitory concentration increases the permeability of the M. vaccae cell wall, which was monitored by cell sensitization to erythromycin and rifampicin. The high permeability of the cell wall to hydrophobic compounds allows enhanced intracellular bioconversion of beta-sitosterol to 4-androsten-3,17-dione (AD) and 1,4-androstadien-3,17-dione (ADD).


Magnetic resonance image segmentation of the compressed spinal cord in patients with degenerative cervical myelopathy using convolutional neural networks.
Spinal cord segmentation is the first step in atlas-based spinal cord image analysis, but segmentation of compressed spinal cords from patients with degenerative cervical myelopathy is challenging. We applied convolutional neural network models to segment the spinal cord from T2-weighted axial magnetic resonance images of DCM patients. Furthermore, we assessed the correlation between the cross-sectional area segmented by this network and the neurological symptoms of the patients. The CNN architecture was built using U-Net and DeepLabv3 + and PyTorch. The CNN was trained on 2762 axial slices from 174 patients, and an additional 517 axial slices from 33 patients were held out for validation and 777 axial slices from 46 patients for testing. The performance of the CNN was evaluated on a test dataset with Dice coefficients as the outcome measure. The ratio of CSA at the maximum compression level to CSA at the C2 level, as segmented by the CNN, was calculated. The correlation between the spinal cord CSA ratio and the Japanese Orthopaedic Association score in DCM patients from the test dataset was investigated using Spearman's rank correlation coefficient. The best Dice coefficient was achieved when U-Net was used as the architecture and EfficientNet-b7 as the model for transfer learning. Spearman's rs between the spinal cord CSA ratio and the JOA score of DCM patients was 0.38 (p = 0.007), showing a weak correlation. Using deep learning with magnetic resonance images of deformed spinal cords as training data, we were able to segment compressed spinal cords of DCM patients with a high concordance with expert manual segmentation. In addition, the spinal cord CSA ratio was weakly, but significantly, correlated with neurological symptoms. Our study demonstrated the first steps needed to implement automated atlas-based analysis of DCM patients.


Activation energy of single-stranded DNA moving through cross-linked polyacrylamide gels at 300 V/cm. Effect of temperature on sequencing rate in high-electric-field capillary gel electrophoresis.
In DNA sequencing, single-stranded DNA fragments are separated by gel electrophoresis. This separation is based on a sieving mechanism where DNA fragments are retarded as they pass through pores in the gel. In this paper, we present the mobility of DNA sequencing fragments as a function of temperature; mobility is determined in 4% T LongRanger gels at an electric field of 300 V/cm. The temperature dependence is compared with the predictions of the biased reptation model. The model predicts that the fragment length for the onset of biased reptation with stretching increases with the square of temperature; the data show that the onset of biased reptation with stretching decreases with temperature. Biased reptation fails to model accurately the temperature dependence of mobility. We analyzed the data and extracted the activation energy for passage of sequencing fragments through the gel. For fragments containing less than ca. 200 bases, the activation energy increases linearly with the number of bases at a rate of 25 J/mol per base; for longer fragments, the activation energy increases at a rate of 6.5 J/mol per base. This transition in the activation energy presumably reflects a change in conformation of the DNA fragments; small fragments exist in a random coil configuration and larger fragments migrate in an elongated configuration.


MRI, CT, US and ERCP in the evaluation of bile duct hamartomas (von Meyenburg complex): a case report.
A case of multiple bile duct hamartomas (von Meyenburg complex) of the liver accompanied by exudative and in part necrotizing pancreatitis is presented. Magnetic resonance imaging (fat suppressed, T2-weighted images with prolonged echo time) could exclude diffuse tumor infiltration of the liver, which had not been possible with CT, sonography, or ERCP. To our knowledge, no comparable case has been reported.


Covariation of soil bacterial composition with plant rarity.
Rare and common plants are predicted to host different rhizospheric microbes. To evaluate this prediction, we used terminal restriction fragment length polymorphism (T-RFLP) analysis to compare rhizospheric bacteria from eight native grass species whose local abundances in their natural ecosystem spanned a 15-fold range. We observed that locally rare versus common plants are associated with divergent bacterial communities.


Disorders of platelet function.
Platelets provide for primary hemostasis by forming a hemostatic plug at sites of vascular damage. They also provide a surface for the assembly of the coagulation protein complexes that generate thrombin, serve as a nidus for fibrin clots, and secrete factors involved in wound repair. Normal platelet function can be divided into four phases: adhesion, aggregation, secretion, and expression of procoagulant activity. Platelet adhesion initiates plug formation as platelets adhere to the connective tissue at the edges of a wound within seconds after vascular damage. When damage occurs in regions of slow blood flow, platelets adhere to subendothelial collagen, fibronectin, and laminin. However, when damage occurs in regions of rapid flow, platelet adhesion requires the presence of subendothelial von Willebrand factor (vWf) and a specific platelet receptor, the glycoprotein Ib/IX (GPIb/IX) complex. Following initial adhesion, platelets aggregate to complete the formation of a hemostatic plug. Platelet aggregation requires active platelet metabolism, platelet stimulation by agonists such as ADP, thrombin, collagen, or epinephrine; the presence of calcium or magnesium ions and specific plasma proteins such as fibrinogen or vWf; and a platelet receptor, the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. Thus, platelet stimulation results in the generation of intracellular second messengers that transmit the stimulus back to the platelet surface, exposing protein binding sites on GPIIb/IIIa. Fibrinogen (or vWf) then binds to GPIIb/IIIa and crosslinks adjacent platelets to produce platelet aggregates. Platelet stimulation also results in platelet secretion and the elaboration of platelet procoagulant activity. During secretion, substances are released to propagate the aggregation response and to promote wound healing; the expression of procoagulant activity localizes thrombin generation to the site of vascular damage. Disorders of platelet function can be divided into those of congenital and those of acquired origin. Although congenital disorders are uncommon, acquired disorders are encountered frequently in clinical practice. Congenital absence of GPIb/IX and GPIIb/IIIa results in the Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT), respectively. Each is an autosomal recessive bleeding disorder in which absence of a protein complex renders the affected platelets incapable of undergoing either vWf-mediated adhesion (BSS) or fibrinogen-mediated aggregation (GT).(ABSTRACT TRUNCATED AT 400 WORDS)


In vitro benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations in primary lymphocytes, smoking, and risk of squamous cell carcinoma of the head and neck.
Cigarette smoking is a major risk factor for squamous cell carcinoma of the head and neck (SCCHN), but only a fraction of those exposed to cigarette smoke develops SCCHN, suggesting variation in individual susceptibility. Tobacco smoke contains a number of carcinogens that cause various kinds of damage to DNA. In this study, we simultaneously measured benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations by the comet assay and the mutagen sensitivity assay, respectively, in cultured primary lymphocytes from newly recruited 123 patients with SCCHN and 136 age- and sex-matched controls. Using the control median as the cut-off, the elevated risk of SCCHN was 2.35 (95% CI, 1.37-4.03), 2.28 (95% CI, 1.34-3.98) and 3.25 (95% CI, 1.85-5.07) for high levels of tail extension, tail length and oliver tail moment of the comet assay, respectively, and 1.75 (95% CI, 1.04-2.94) for high levels of chromosomal aberrations of the mutagen sensitivity assay. The effects of these 2 types of measurements were additive; subjects with high levels of both DNA damage and chromosomal aberrations had a 4.77-fold increased risk (95% CI, 2.73-8.36) of SCCHN. Cigarette smoking further elevated this risk to more than 20-fold (OR 23.6; 95% CI, 8.92-62.3). These data support our previous finding that suboptimal repair contributed to susceptibility to SCCHN and the new data further suggests a possible gene-environment interaction that may play an important role in the etiology of SCCHN. Further validation studies are warranted.