Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.
Myotonic dystrophy (DM) is caused by a CTG expansion in the 3' untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal cells expressing transcripts that contain CUG repeats. Altered expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis.


Activation of TGF-β1 promoter by hepatitis C virus-induced AP-1 and Sp1: role of TGF-β1 in hepatic stellate cell activation and invasion.
Our previous studies have shown the induction and maturation of transforming growth factor-beta 1 (TGF-β1) in HCV-infected human hepatoma cells. In this study, we have investigated the molecular mechanism of TGF-β1 gene expression in response to HCV infection. We demonstrate that HCV-induced transcription factors AP-1, Sp1, NF-κB and STAT-3 are involved in TGF-β1 gene expression. Using chromatin immunoprecipitation (ChIP) assay, we further show that AP-1 and Sp1 interact with TGF-b1 promoter in vivo in HCV-infected cells. In addition, we demonstrate that HCV-induced TGF-β1 gene expression is mediated by the activation of cellular kinases such as p38 MAPK, Src, JNK, and MEK1/2. Next, we determined the role of secreted bioactive TGF-β1 in human hepatic stellate cells (HSCs) activation and invasion. Using siRNA approach, we show that HCV-induced bioactive TGF-β1 is critical for the induction of alpha smooth muscle actin (α-SMA) and type 1 collagen, the markers of HSCs activation and proliferation. We further demonstrate the potential role of HCV-induced bioactive TGF-β1 in HSCs invasion/cell migration using a transwell Boyden chamber. Our results also suggest the role of HCV-induced TGF-β1 in HCV replication and release. Collectively, these observations provide insight into the mechanism of TGF-β1 promoter activation, as well as HSCs activation and invasion, which likely manifests in liver fibrosis associated with HCV infection.


Disrupting the cortical actin cytoskeleton points to two distinct mechanisms of yeast [PSI+] prion formation.
Mammalian and fungal prions arise de novo; however, the mechanism is poorly understood in molecular terms. One strong possibility is that oxidative damage to the non-prion form of a protein may be an important trigger influencing the formation of its heritable prion conformation. We have examined the oxidative stress-induced formation of the yeast [PSI+] prion, which is the altered conformation of the Sup35 translation termination factor. We used tandem affinity purification (TAP) and mass spectrometry to identify the proteins which associate with Sup35 in a tsa1 tsa2 antioxidant mutant to address the mechanism by which Sup35 forms the [PSI+] prion during oxidative stress conditions. This analysis identified several components of the cortical actin cytoskeleton including the Abp1 actin nucleation promoting factor, and we show that deletion of the ABP1 gene abrogates oxidant-induced [PSI+] prion formation. The frequency of spontaneous [PSI+] prion formation can be increased by overexpression of Sup35 since the excess Sup35 increases the probability of forming prion seeds. In contrast to oxidant-induced [PSI+] prion formation, overexpression-induced [PSI+] prion formation was only modestly affected in an abp1 mutant. Furthermore, treating yeast cells with latrunculin A to disrupt the formation of actin cables and patches abrogated oxidant-induced, but not overexpression-induced [PSI+] prion formation, suggesting a mechanistic difference in prion formation. [PIN+], the prion form of Rnq1, localizes to the IPOD (insoluble protein deposit) and is thought to influence the aggregation of other proteins. We show Sup35 becomes oxidized and aggregates during oxidative stress conditions, but does not co-localize with Rnq1 in an abp1 mutant which may account for the reduced frequency of [PSI+] prion formation.


Intracellular pH controls WNT downstream of glycolysis in amniote embryos.
Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic mesoderm, which control posterior elongation1, exhibit a high level of aerobic glycolysis that is reminiscent of the metabolic status of cancer cells experiencing the Warburg effect2,3. Glycolytic activity downstream of fibroblast growth factor controls WNT signalling in the tail bud3. In the neuromesodermal precursors of the tail bud4, WNT signalling promotes the mesodermal fate that is required for sustained axial elongation, at the expense of the neural fate3,5. How glycolysis regulates WNT signalling in the tail bud is currently unknown. Here we used chicken embryos and human tail bud-like cells differentiated in vitro from induced pluripotent stem cells to show that these cells exhibit an inverted pH gradient, with the extracellular pH lower than the intracellular pH, as observed in cancer cells6. Our data suggest that glycolysis increases extrusion of lactate coupled to protons via the monocarboxylate symporters. This contributes to elevating the intracellular pH in these cells, which creates a favourable chemical environment for non-enzymatic β-catenin acetylation downstream of WNT signalling. As acetylated β-catenin promotes mesodermal rather than neural fate7, this ultimately leads to activation of mesodermal transcriptional WNT targets and specification of the paraxial mesoderm in tail bud precursors. Our work supports the notion that some tumour cells reactivate a developmental metabolic programme.


[A case of SPT therapy( S-1+CDDP+trastuzumab) was successful for HER2-positive gastric cancer accompanied by distant lymph node metastasis].
A 63-year-old man visited our clinic with a chief complaint of a left axillary mass, and after a series of examinations, gastric cancer was diagnosed. Histopathological examination revealed a human epidermal growth factor receptor (HER)-2- positive( immunohistochemistry[ IHC], 2+; fluorescence in situ hybridization[ FISH], positive) poorly differentiated adenocarcinoma, and SPT therapy( S-1 at 120 mg/m2/day+cisplatin[ CDDP] at 60 mg/m2+trastuzumab at 8 mg/kg) was initiated. The primary lesion and swollen lymph nodes initially decreased markedly in size; however, the lymph node swelling worsened at 186 days( 6.2 months) after the initiation of treatment. Progressive disease( PD) was diagnosed, and SPT therapy was terminated. One cycle of S-1+docetaxel was administered as second-line therapy, but the regimen was changed to docetaxel monotherapy due to adverse effects. After 5 cycles of this treatment, the primary lesion had decreased in size and the lymphadenopathy disappeared. Positron emission tomography( PET)-computed tomography (CT) revealed fluorodeoxyglucose( F18)( FDG) accumulation only in the primary lesion, and therefore, with the patient's informed consent distal gastrectomy was performed approximately 14 months after the first treatment. The postoperative diagnosis was gastric cancer fStage IA (T1a, N0, and M0). Here, we discuss a case of HER2-positive gastric cancer with references. Among the advanced recurrent gastric cancers tested between April 2011 and February 2013, 16.4% (11/67) were HER2-positive.


Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies.
Skeletal muscle, which accounts for approximately 40% of total body weight, is one of the most dynamic and plastic tissues in the human body and plays a vital role in movement, posture and force production. More than just a component of the locomotor system, skeletal muscle functions as an endocrine organ capable of producing and secreting hundreds of bioactive molecules. Therefore, maintaining healthy skeletal muscles is crucial for supporting overall body health. Various pathological conditions, such as prolonged immobilization, cachexia, aging, drug-induced toxicity, and cardiovascular diseases (CVDs), can disrupt the balance between muscle protein synthesis and degradation, leading to skeletal muscle atrophy. Mitochondrial dysfunction is a major contributing mechanism to skeletal muscle atrophy, as it plays crucial roles in various biological processes, including energy production, metabolic flexibility, maintenance of redox homeostasis, and regulation of apoptosis. In this review, we critically examine recent knowledge regarding the causes of muscle atrophy (disuse, cachexia, aging, etc.) and its contribution to CVDs. Additionally, we highlight the mitochondrial signaling pathways involvement to skeletal muscle atrophy, such as the ubiquitin-proteasome system, autophagy and mitophagy, mitochondrial fission-fusion, and mitochondrial biogenesis. Furthermore, we discuss current strategies, including exercise, mitochondria-targeted antioxidants, in vivo transfection of PGC-1α, and the potential use of mitochondrial transplantation as a possible therapeutic approach.


C3b2-IgG complexes retain dimeric C3 fragments at all levels of inactivation.
C3b2-IgG complexes are formed during complement activation in serum by attachment of two C3b molecules (the proteolytically activated form of C3) to one IgG heavy chain (IgG HC) via ester bonds. Because of the presence of two C3b molecules, these complexes are very efficient activators of the alternative complement pathway. Likewise, dimeric C3b is known to enhance complement receptor 1-dependent phagocytosis, and dimeric C3d (the smallest thioester-containing fragment of C3) linked to a protein antigen facilitates CR2-dependent B-cell proliferation. Because the efficiency of all these interactions depends on the number of C3 fragments, we investigated whether C3b2-IgG complexes retained dimeric structure upon physiological inactivation. We used two-dimensional SDS-PAGE and Western blot to study the arrangement of the C3b molecules by analyzing the fragmentation pattern after cleavage of the ester bonds. Upon inactivation with factors H and I, a 185-kDa band was generated under reducing conditions. It released IgG HC and the 65-kDa fragment of C3b alpha' chain after hydrolysis of the ester bonds with hydroxylamine. The two C3b molecules were not 65-kDa-to-40-kDa linked, because neither ester-bonded 65 kDa HC nor 65 kDa-40 kDa fragments were observed, nor was a 40-kDa peptide released after hydroxylamine cleavage. Factor I and CR1 cleaved the C3b2-IgG molecule to its final physiological product, C3dg2-IgG, which migrated as a 133-kDa fragment in reduced form. This fragment released exclusively C3dg (the final physiological product of C3b inactivation by factor I) and IgG HC. C3dg2-HC appeared as a double band on SDS-PAGE only at low gel porosity, suggesting the presence of two conformers of the same composition. Our results suggest that, upon physiological inactivation, C3b2-IgG complexes retain dimeric inactivated C3b and C3dg, which allows bivalent binding to the corresponding complement receptors.


[Regulations of function and maturation of plasmacytoid dendritic cells from primary immune thrombocytopenia patients by triptolide].
To explore the mechanism of immunomodulatory activity of triptolide on primary immune thrombocytopenia (ITP)patients-derived plasmacytoid dendritic cells (pDCs). pDCs in peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response (ITP-CR, group 2) and healthy donors (group 3) were sorted by flow cytometry, then incubated with triptolide at 0, 5, 10 or 30 µg/L. After 24 hours, we collected the supernatants and then detected the concentrations of IFN-α, IL-6 and TNF-α using ELISA. After 5 days, the cultured cells were collected and CD11c, CD80 and CD86 expressions of myeloid dendritic cells (mDCs) were analyzed by flow cytometry, the morphology of mDC was observed by light microscope and electron microscope. After incubation with triptolide at 10 µg/L, the levels of IFN-α, IL-6 and TNF-α in group 1 \[(451.32 ± 85.77) ng/L, (105.68 ± 23.85) ng/L and (135.78 ± 30.62) ng/L\] and group 2 \[(391.71 ± 72.49) ng/L, (84.73 ± 17.77) ng/L and (108.16 ± 23.21) ng/L\] were significantly higher than those in group 3 \[(335.51 ± 67.54) ng/L, (73.62 ± 21.82) ng/L and (95.58 ± 32.85) ng/L\] (all P < 0.05); the levels of IFN-α, IL-6 and TNF-α in group 1 were significantly higher than those in group 2 (all P < 0.05) in a dose-dependent manner (P < 0.05). CD11c, CD80 and CD86 expressions of mDC in group1 and group 2 were significantly higher than those in group 3 (all P < 0.05); CD11c, CD80 and CD86 expressions of mDC in group 1 were significantly higher than those in group 2 (all P < 0.05) also in a dose-dependent manner (all P < 0.05). Triptolide could inhibit pDCs from differentiation into mDCs, the latter displayed more immature morphology than untreated-pDCs. Triptolide could decrease the immune function of pDCs from ITP, inhibit pDCs from differentiation and maturation.


Screening for diabetic retinopathy in a clinical setting: a comparison of direct ophthalmoscopy by primary care physicians with fundus photography.
Type II diabetes mellitus is a major health problem among Native Americans, and diabetic retinopathy is a frequent complication of this disease. Screening for retinopathy can identify early disease and prevent major vision loss, but the most cost-effective screening method has not yet been determined. In a rural clinic that served more than 400 Native Americans with diabetes, we compared the accuracy of referrals made based on two screening methods: ophthalmoscopy by trained primary care physicians and seven-view nonstereoscopic, mydriatic fundal photography read by two general ophthalmologists and a retinal specialist. Patients in whom abnormal findings were detected by either screening method were then referred to a general ophthalmologist for further evaluation. Two hundred forty-three examinations were performed and 83 referrals made. Both screening methods had high sensitivity for referring patients with retinopathy that required treatment or follow-up sooner than 1 year (100% for direct ophthalmoscopy by primary care physicians, 94% for the general ophthalmologist photography readers, and 100% for the retinal specialist reader). The calculated costs of screening by direct ophthalmoscopy and by retinal photography were 64% less and 44% to 35% less, respectively, than the cost of yearly ophthalmological examinations by ophthalmologists. Careful screening for treatable diabetic eye disease by trained primary care physicians proved to be a clinically acceptable, cost-effective strategy. Screening methods for diabetic retinopathy should be evaluated based on the absolute sensitivity, specificity, and predictive values of their ability to correctly refer patients rather than their diagnostic accuracy.


Micromanipulation of sonoluminescing bubbles.
Micromanipulation of sonoluminescing bubbles is achieved by generating a complex sound field consisting of spatially distributed modes of higher harmonics of a basic driving frequency. Bubbles can be manipulated in space and shifted to any desired spot. The interaction with the complex sound field also allows for specification of the violence of a bubble collapse.


[Surgical indication in myelomeningoceles (author's transl)].
Myelomeningoceles underlie critical indication for surgical closure. Clearcut contra indications such as total congenital hydrocephalus, intracranial haemorrhage and cerebral bith-traumatic lesions, severe forms of gibbus and the combination with other severe malformations eliminate the right of active surgery. The conservative treatment neither corresponds to therapeutic nihilism nor is it the inevitability of a lethal outcome. The author does not agree with conceptions such as selection of criteria of selection according to Lorber.


Visualization and model building in medical imaging.
We present technologies and ideas, developed from the JFIT 'Active Stereo Probe Project', which are applicable to problems within medical measurement and monitoring. Two related areas are considered. The first concerns patient body surface modelling. During the project two state-of-the-art non-contact surface measurement techniques have been developed which are applicable to medical situations requiring dense and accurate body surface modelling. Such applications include, for example, prosthetic appliance fabrication, presurgical planning and non-invasive deformity analysis. The second is concerned with overlay projection. Using this enabling technology the information content of a scene can be enhanced as an aid to medical personnel. Results and illustrative applications of the newly developed technology are presented.


Lung delayed-type hypersensitivity in stressed mice.
The influence of an immobilization stressor on lung cellular immune responses was studied. Delayed-type hypersensitivity to sheep erythrocytes was used to evaluate in vivo lung cellular immunity. Mice were sensitized intravenously and challenged intratracheally with sheep erythrocytes. Three hours prior to challenge all mice were injected intravenously with chromium-51 labeled mononuclear cells from syngeneic mice. The delayed-type hypersensitivity response was measured by counting the radioactivity within the lung 48 hours after challenge. Immobilization for 2.5 hours immediately before challenge suppressed lung delayed-type hypersensitivity. Adrenalectomy abolished the immobilization-induced decrease in delayed-type hypersensitivity. These data indicate an adrenal gland involvement in stress-induced decreases in lung cellular immune reactions.


Psychiatric adjustment in the year after meningococcal disease in childhood.
To assess psychiatric status after meningococcal disease. Cohort study of 66 children (34 boys, 32 girls) ages 4 to 17 years admitted to pediatric hospitals with meningococcal disease. The main outcome measure was psychiatric disorder (1-year period and point prevalence on the Schedule for Affective Disorders and Schizophrenia for School-Age Children interview for children 6 years or older; point prevalence in younger children on the Behavior Screening Questionnaire). During the course of the year after discharge from hospital, psychiatric disorders were identified in 23 of 40 (57%) children ages 6 years or older. The most common primary disorders were depressive, oppositional defiant, and anxiety disorders. At the time of 12-month follow-up, psychiatric disorders were present in 13 of 40 (32%) of those ages 6 or older and in 7 of 26 (26%) under 6 years old. Two children had a diagnosis of posttraumatic stress disorder. Logistic regression analysis showed that global meningococcal illness severity score, clinical shock on admission, and impairing premorbid emotional and behavioral problems in the child were independent predictors of psychiatric disorder at 12-month follow-up. Psychiatric disorders are common in the year after meningococcal disease. Especially at risk are children who are severely medically ill and those with more impairing premorbid emotional and behavioral problems.


Extracorporeal Membrane Oxygenation in Pregnant Women With COVID-19.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and lung involvement is common. Patients with COVID-19 may progress to acute respiratory distress syndrome (ARDS) for which they may require mechanical ventilation. When conventional ventilation strategies are unable to achieve the desired oxygenation and gas exchange, extracorporeal membrane oxygenation (ECMO) might be an option in selected patients. The literature on the use of ECMO in peripartum women with COVID-19 is limited. We present a series of ten cases involving pregnant and recently pregnant women who rapidly developed ARDS after the onset of COVID-19 for which they received ECMO. Nine of the 10 patients survived intensive care unit discharge after a gradual recovery of their pulmonary function and weaning from mechanical ventilation and ECMO. In addition, 9 out of the 10 delivered neonates survived neonatal intensive care unit discharge.


In vivo and in vitro acylation of polypeptides in Vibrio harveyi: identification of proteins involved in aldehyde production for bioluminescence.
Incubation of soluble extracts from Vibrio harveyi with [3H]tetradecanoic acid (+ ATP) resulted in the acylation of several polypeptides, including proteins with molecular masses near 20 kilodaltons (kDa), and at least five polypeptides in the 30- to 60-kDa range. However, in growing cells pulse-labeled in vivo with [3H]tetradecanoic acid, only three of these polypeptides, with apparent molecular masses of 54, 42, and 32 kDa, were specifically labeled. When extracts were acylated with [3H] tetradecanoyl coenzyme A, on the other hand, only the 32-kDa polypeptide was labeled. When luciferase-containing dark mutants of V. harveyi were investigated, acylated 32-kDa polypeptide was not detected in a fatty acid-stimulated mutant, whereas the 42-kDa polypeptide appeared to be lacking in a mutant defective in aldehyde synthesis. Acylation of both of these polypeptides also increased specifically during induction of bioluminescence in V. harveyi. These results suggest that the role of the 32-kDa polypeptide is to supply free fatty acids, whereas the 42-kDa protein may be responsible for activation of fatty acids for their subsequent reduction to form the aldehyde substrates of the bioluminescent reaction.


Incidence and predictors of mortality among patients with head injury admitted to Hawassa University Comprehensive Specialized Hospital, Southern Ethiopia: A retrospective follow-up study.
Head injury is the leading cause of morbidity and mortality throughout the world, especially in resource-limited countries including Ethiopia. However, little is known about the mortality rate and its predictors among these patients in Ethiopia. Thus, the study aims to assess the incidence rate of mortality and its predictors among patients with head injury admitted at Hawassa University Comprehensive Specialized Hospital. Institutional based retrospective follow-up study was conducted among 1220 randomly selected head injury patients admitted from July 2017 to July 2019. Bivariable and multivariable Cox regression models were fitted to identify the predictors of mortality. Proportionality assumption was tested by a global test based on the Schoenfeld residuals test. The incidence of the mortality rate was 2.26 (95%CI: 1.9-2.6) per 100-person day observation. The independent predictors of time to death were age above 65 years (AHR:3.49, 95%CI:1.63, 7.48), severe TBI (AHR: 8.8, 95%CI:5.13, 15.0), moderate TBI (AHR:3, 95%CI:1.73,5.31), hypotension (AHR:1.72, 95%CI: 1.11,2.66), hypoxia (AHR:1.92, 95%CI: 1.33,2.76), hyperthermia (AHR:1.8, 95%CI: 1.23,2.63) and hypoglycemic (AHR:1.94, 95%CI: 1.34, 2.81) positively associated with mortality, while underwent neurosurgery was negatively associated with mortality (AHR: 0.25, 95% CI: 0.11,0.53). The incidence of mortality rate among head injury patients was high. Older age, moderate and severe TBI, hypotension and hypoxia at admission, neurosurgical procedure, and the episode of hyperthermia and hypoglycemia during hospitalization were the independent predictors of mortality among head injury patients. Therefore, intervention to reduce earlier deaths should focus on the prevention of secondary brain insults.


[A case report of reversible biliary pseudolithiasis caused by ceftriaxone in childhood: does the problem deserve greater attention?].
The authors report the case of a nine-year-old girl admitted to hospital with signs of meningeal irritation during the course of hyperpyretic phlogosis of the upper airways who presented, after 6 days' treatment with CFTX, at a dose of 50 mg/kg/day (1.5 g/day), therefore at the maximum recommended dose for the antibiotic in question, symptomatic cholecystic "pseudolithiasis" which resolved two weeks after the suspension of the drug. This case appears to concord with recent reports of "pseudolithiasis" in childhood that appeared with doses not regarded as being at risk, and it draws attention to the etiopathogenetic importance of other factors, including familial recurrence. The authors recommend a reasonable use of CFTX and the need to be "vigilant" both in relation to the onset and evolution of the clinical condition described above.


Fabrication of Sealed Nanostraw Microdevices for Oral Drug Delivery.
The oral route is preferred for systemic drug administration and provides direct access to diseased tissue of the gastrointestinal (GI) tract. However, many drugs have poor absorption upon oral administration due to damaging enzymatic and pH conditions, mucus and cellular permeation barriers, and limited time for drug dissolution. To overcome these limitations and enhance oral drug absorption, micron-scale devices with planar, asymmetric geometries, termed microdevices, have been designed to adhere to the lining of the GI tract and release drug at high concentrations directly toward GI epithelium. Here we seal microdevices with nanostraw membranes-porous nanostructured biomolecule delivery substrates-to enhance the properties of these devices. We demonstrate that the nanostraws facilitate facile drug loading and tunable drug release, limit the influx of external molecules into the sealed drug reservoir, and increase the adhesion of devices to epithelial tissue. These findings highlight the potential of nanostraw microdevices to enhance the oral absorption of a wide range of therapeutics by binding to the lining of the GI tract, providing prolonged and proximal drug release, and reducing the exposure of their payload to drug-degrading biomolecules.


A comparative study on postoperative mortality prediction of SFLI scoring system and Child-Pugh classification in patients with hepatocellular carcinoma.
In our previous study, we have established the clinical significance of the SFLI (scoring formula of liver injury), the purpose of this study was to compare the SFLI system and the Child-Pugh grading system in the prediction of postoperative mortality in patients with hepatocellular carcinoma (HCC). 114 patients with HCC who underwent surgical treatment were enrolled. According to the requirement of the indicators for the Child-Pugh classification, various indices (including albumin [ALB], total bilirubin [TBIL], prothrombin time [PT], ascites, and hepatic encephalopathy) were considered in these patients before surgery, and then Child-Pugh grading was performed. Similarly, the serum biochemical markers including ALB, pre-albumin (PA), TBIL, serum creatining (SCR), international normalized ratio (INR), alanine transminase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (ggr;-GT), alkaline phosphatase (ALP), PT, activated partial thromboplastin time (APTT), and thrombine time (TT) were collected before surgery for SFLI analysis. The predicted postoperative mortality rates of these two scoring models and their diagnostic efficacy were analyzed and compared. According to the Child-Pugh grading system, in level A, B and C were 75, 35, and 4 cases respectively, and the corresponding mortality rates were 1.3% (1/75), 17.1% (6/35) and 75% (3/4). Meanwhile, according to the SLFI classification, the number of patients in the grade I, I+, II, and III were 36, 29, 28, and 21, respectively, and the corresponding mortality rates were 0, 0, 14.3% (4/28), and 28.6% (6/21), respectively. The patient mortality rate increased significantly with increasing grading (p<0.01). These two classification methods were further compared using ROC analysis, in which the area under the curve (AUC) for the Child-Pugh method was 10.2% with a 95% confidence interval (95% CI) 17-18, and the AUC of SFLI was 88.2% with a 95% CI 80-96. The SFLI scoring system is very useful in the assessment of liver function and postoperative mortality, and its grading standard is much better than the traditional Child-Pugh classification in many aspects.


Safety culture in high-risk industries.
This paper addresses the question of whether adopting safety culture improves hazard prevention in enterprises characterized by high primary risk. To answer this question, sample underground coal mines were examined to investigate the basic elements of the safety culture of employees. This paper presents the results of a diagnosis of the basic elements of the safety culture of supervisors (midlevel managers) and blue-collar workers in 3 underground coal mines. The study used 2 techniques: a Likert-type scale and a questionnaire. The results indicate the need to introduce changes in the safety culture of underground coal mine employees. This study also presents the conditions for improvement. Special attention was paid to (a) the conditions for improving safety culture and (b) a programme for modifying risky behaviours.


Simple and rapid electrochemical monitoring for depolymerization of polyamic acid.
Excellent thermal and mechanical properties of aromatic polyimides (PIs) make them attractive materials in various fields. PIs is performed using polyamic acid (PAA) precursors due to their limited solubility. However, PAAs can be easily depolymerized by moisture and heat, which can degrade the properties of PIs. Therefore, quality control of PAAs is an important task in researches and industrial applications. Here, we propose a simple, rapid, and novel method to observe the depolymerization of PAAs. The method is based on the principle that, as the molecular weight of the polymer decreases, the solution viscosity decreases, and the viscosity of the solution can be easily and rapidly measured using electrochemistry. We accelerated depolymerization by applying heat to a PAA solution and measured the change in viscosity of the solution through cyclic voltammetry. The proposed method, which also makes it possible to determine the dynamic viscosity of a polymer solution, is presented as a model system to observe state changes in various polymers.


[Screening of people with fever returning to Denmark from "the tropics"].
A number of febrile diseases imported from the tropics, above all malaria, may, if left untreated, endanger the life of the patient. Microscopy of malaria slides without delay is by far the most important diagnostic tool in all patients who may have been exposed to infection. An accurate, detailed travel history, a knowledge of infections prevalent in areas where the patient has been and a thorough physical examination are essential. However, the majority of persons with fever after travel have a cosmopolitan etiology to their disease. If investigations suggest a possibly exotic yet not clear-cut cause of the febrile condition, it may be desirable to consult a physician with expertise in tropical medicine.


Acute Intravenous Calcium Antagonist for Suspected Hemiplegic Migraine - A Case Story.
Stroke mimics, like attacks of hemiplegic migraine, are challenging in acute stroke evaluation. We present a 28-year-old woman with a suspected hemiplegic migraine attack with left-sided hemiparalysis. Brain CT with perfusion imaging 1 h 54 min after symptom onset revealed hypoperfusion in the right hemisphere. The patient was treated with intravenous recombinant tissue plasminogen activator (rtPA) with no effect. After a subsequent intravenous verapamil infusion, the patient gained full motor function within 10 min. Brain magnetic resonance imaging (MRI) performed 5 h 46 min after symptom onset revealed diffusion restriction in the same area as the hypoperfusion on CT. There were no notable changes on T2 images. The patient stayed clinically in remission, except for reduced sensation for all modalities on the extremities on the left side. Although brain CT 24 h after symptom onset revealed an edema in the same area, an MRI performed 17 days later showed no new infarctions. Young patients with a history of migraine with aura admitted with symptoms of acute ischemic stroke are at risk of insufficient treatment. Calcium antagonists might be considered if there is no effect of first-line treatment with rtPA.


Endovascular Treatment and Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability or Dementia: A Scientific Statement From the American Heart Association/American Stroke Association.
Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.


Type 1 and type 2 responses to Leishmania major.
Leishmania major is a protozoan parasite that is transmitted to the mammalian host by its sand fly vector when the fly probes in the host's skin for a blood meal and injects the parasite within its saliva. In mice experimentally infected with L. major, outgrowth of CD4 type 1 (Th1) cells leads to resolution of the infection, but outgrowth of type 2 (Th2) cells exacerbates disease. To design an effective vaccine against the parasite (and other pathogens that induce polarized Th1 and Th2 responses), we must determine the mechanism underlying this phenomenon so that we can design the vaccine to elicit the appropriate (i.e., protective) Th cell. Recent work indicates that Th bias is influenced by a number of signals delivered by antigen-presenting cells, including cytokines and co-stimulatory molecules. Moreover, recent work also suggests that sand fly saliva influences the immune response to L. major and Th polarization. Determining the mechanisms that lead to polarized Th responses should expand our knowledge regarding immunity to L. major, and should add to our understanding of immunoregulation in general.


MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin.
We attempt to demonstrate the regulatory role of miR-200c in glioma progression and its mechanisms behind. Here, we show that miR-200c expression was significantly reduced in the glioma tissues compared to paratumor tissues, especially in malignant glioma. Exogenous overexpression of miR-200c inhibited the proliferation and invasion of glioma cells. In addition, the in vivo mouse xenograft model showed that miR-200c inhibited glioma growth and liver metastasis, which is mainly regulated by targeting moesin (MSN). We demonstrated that the expression of MSN in glioma specimens were negatively correlated with miR-200c expression, and MSN overexpression rescued the phenotype about cell proliferation and invasion induced by miR-200c. Moreover, knockdown of MSN was able to mimic the effects induced by miR-200c in glioma cells. These results indicate that miR-200c plays an important role in the regulation of glioma through targeting MSN.


Livestock wastewater treatment using aerobic granular sludge.
The present study demonstrated that aerobic granular sludge is capable of treating livestock wastewater from a cattle farm in a sequencing batch reactor (SBR) without the presence of support material. A lab scale SBR was operated for 80 d using 4 h cycle time with an organic loading rate (OLR) of 9 kg COD m(-3) d(-1). Results showed that the aerobic granules were growing from 0.1 to 4.1 mm towards the end of the experimental period. The sludge volume index (SVI) was 42 ml g(-1) while the biomass concentration in the reactor grew up to 10.3 g L(-1) represent excellent biomass separation and good settling ability of the granules. During this period, maximum COD, TN and TP removal efficiencies (74%, 73% and 70%, respectively) were observed in the SBR system, confirming high microbial activity in the SBR system.


Crush Injury-induced Finger Compartment Syndrome: A Case Report and Literature Review.
Isolated finger compartment syndrome is an uncommon condition and is not well-documented. It is usually associated with pain, decreased sensation, and intra-compartmental swelling. We present the case of a finger fracture after a crush injury that developed compartment syndrome, which responded well after surgical fixation and midline skin incision for digital decompression. A 20-year-old male with a history of a 200 lb crush-injury to the left index finger 24 hours prior presented to the emergency department with decreased sensation and range of motion, deformity, increasing pallor, and severe pain. Radiographs demonstrated a middle phalanx fracture of the index finger. Digital decompression of the index finger through a radial approach, along the middle line, and open reduction internal fixation of the middle phalanx improved perfusion almost immediately. The patient continued to improve at his one-week, 12-week, and six-month follow-up appointments, with a normal neurovascular exam, a capillary refill of less than two seconds, and, ultimately, he was able to make a full composite fist. Though finger compartment syndrome is uncommon, it should be suspected in cases where the patient demonstrates hallmark clinical signs and symptoms. Compartment syndrome is a clinical diagnosis that requires urgent diagnosis and intervention and must be suspected regardless of the anatomic location of the injury.


FR4-based electromagnetic scanning micro-grating integrated with an angle sensor for a low-cost NIR micro-spectrometer.
Aiming to implement a low-cost single-photodetector-based NIR micro-spectrometer, we present a novel flame retardant 4 (FR4)-driven micro-grating for spectral dispersion and spatial scanning. It consists of a silicon blazed grating directly bonded onto the FR4 actuator platform and an integrated differential electromagnetic angle sensor. Owing to the better shock and vibration reliability, larger aperture, shorter fabrication cycle, and much lower cost, it may be a potential alternative to conventional silicon microelectromechanical systems scanning micro-gratings. The micro-spectrometer prototype based on this device shows a spectral range of 800-1800 nm, a spectral accuracy of ±1.3 nm, and a 10 nm spectral resolution.


Encapsulation of 2-3-nm-sized ZnO quantum dots in a SiO2 matrix and observation of negative photoconductivity.
Quantum dots (QDs) of ZnO of 2-4 nm size have been encapsulated within a SiO(2) matrix using aqueous chemically grown ZnO nanoparticles in a precursor of tetraethyl orthosilicate. The microstructure shows almost a uniform embedment of the QDs in the SiO(2) matrix, resulting in a ZnO QDs-SiO(2) composite structure. The photocurrent transients of the composite show an instant fall in the current followed by an exponential decay under ultraviolet (UV) illumination, causing negative photoconductivity (NPC), in contrast to the positive photoconductivity in only ZnO nanoparticles. The interface defect states due to the presence of the SiO(2) network around ZnO act as charge trap centers for the photoexcited electrons and are responsible for the NPC. The presence of interface-trapped charges under UV illumination has been further confirmed from capacitance-voltage measurements.


Word length and lexical activation: longer is better.
Many models of spoken word recognition posit the existence of lexical and sublexical representations, with excitatory and inhibitory mechanisms used to affect the activation levels of such representations. Bottom-up evidence provides excitatory input, and inhibition from phonetically similar representations leads to lexical competition. In such a system, long words should produce stronger lexical activation than short words, for 2 reasons: Long words provide more bottom-up evidence than short words, and short words are subject to greater inhibition due to the existence of more similar words. Four experiments provide evidence for this view. In addition, reaction-time-based partitioning of the data shows that long words generate greater activation that is available both earlier and for a longer time than is the case for short words. As a result, lexical influences on phoneme identification are extremely robust for long words but are quite fragile and condition-dependent for short words. Models of word recognition must consider words of all lengths to capture the true dynamics of lexical activation.


Enantiomeric Excess-Tuned 2D Structural Transition: From Heterochiral to Homochiral Supramolecular Assemblies.
Spontaneous resolution of enantiomers is an intriguing and important phenomenon in surface chirality studies. Herein, we report on a two-dimensional (2D) structural transition from the heterochiral to homochiral assembly tuned by changing the enantiomeric excess (ee) of enantiomers in the solution phase. Enantiomers cocrystallize as racemates on the surface when the ee of the R-enantiomer (or S-enantiomer) remains below a critical value, whereas chiral segregation is achieved, and globally homochiral surfaces composed of exclusively one enantiomer are obtained as the critical ee is exceeded. The heterochiral-homochiral transition is ascribed to the formation of energetically unfavored homochiral molecular dimers under the control of the majority-rules principle at high ee values. Such results present an intriguing phenomenon in chiral ordering at surfaces, promising a new enlightenment toward understanding chiral resolution and the evolution of chirality.


Rising PSA during Testosterone Replacement Therapy.
Although testosterone replacement therapy (TRT) is indicated for the management of symptomatic hypogonadism, there is still controversy over whether TRT should be administered to middle-aged men for the clinical manifestations of andropause, regardless of whether the serum testosterone levels are depressed or not. Side effects of TRT may include fluid retention, gynecomastia, polycythemia, and exacerbation of existing prostate cancer. As a result, patients on TRT require meticulous surveillance including regular digital rectal examination and serum prostate-specific antigen (PSA) testing. Herein, we present the case of a middle-aged man with andropause and a rising PSA on TRT.


Mating competitiveness of sterile male Anopheles coluzzii in large cages.
Understanding the factors that account for male mating competitiveness is critical to the development of the sterile insect technique (SIT). Here, the effects of partial sterilization with 90 Gy of radiation on sexual competitiveness of Anopheles coluzzii allowed to mate in different ratios of sterile to untreated males have been assessed. Moreover, competitiveness was compared between males allowed one versus two days of contact with females. Sterile and untreated males four to six days of age were released in large cages (~1.75 sq m) with females of similar age at the following ratios of sterile males: untreated males: untreated virgin females: 100:100:100, 300:100:100, 500:100:100 (three replicates of each) and left for two days. Competitiveness was determined by assessing the egg hatch rate and the insemination rate, determined by dissecting recaptured females. An additional experiment was conducted with a ratio of 500:100:100 and a mating period of either one or two days. Two controls of 0:100:100 (untreated control) and 100:0:100 (sterile control) were used in each experiment. When males and females consort for two days with different ratios, a significant difference in insemination rate was observed between ratio treatments. The competitiveness index (C) of sterile males compared to controls was 0.53. The number of days of exposure to mates significantly increased the insemination rate, as did the increased number of males present in the untreated: sterile male ratio treatments, but the number of days of exposure did not have any effect on the hatch rate. The comparability of the hatch rates between experiments suggest that An. coluzzii mating competitiveness experiments in large cages could be run for one instead of two days, shortening the required length of the experiment. Sterilized males were half as competitive as untreated males, but an effective release ratio of at least five sterile for one untreated male has the potential to impact the fertility of a wild female population. However, further trials in field conditions with wild males and females should be undertaken to estimate the ratio of sterile males to wild males required to produce an effect on wild populations.


Molecular stability and function of hemoglobins Hasharon (alpha(2)47 (CD5)Asp----His beta 2) and Hasharon (alpha(2)47 (CD5)Asp----His delta 2).
The molecular stability and function of hemoglobin (Hb) Hasharon (alpha 2 H beta 2) and Hb Hasharon2 (alpha 2 H delta 2) were studied and compared to Hbs A, A2 and S. Hb Hasharon and Hb Hasharon2 had slightly lower P50 values than Hb A and Hb A2 but had normal responses to organic phosphates. The molecular stability of Hb Hasharon and Hb Hasharon2 (as measured by mechanical shaking and heat denaturation at 60 degrees C) were less than Hb A and Hb A2 but greater than Hb S in the oxy- and carbonmonoxy-forms. In the met-form, however, Hb Hasharon and Hb Hasharon2 were less stable than hemoglobins S, A and A2. The oxy-form of Hb Hasharon forms methemoglobin at a faster rate than Hb A and Hb S. The mechanical and heat stabilities and the rate of methemoglobin formation of oxy-Hb Hasharon were studied in the presence of sulfisoxazole. This drug increased the rate of methemoglobin formation, thus causing a further decrease in the stability of Hb Hasharon. The relationship between these laboratory findings and previously observed clinical findings associated with Hb Hasharon are discussed.


[The applied research on neural network filtrated by rough-set in insect taxonomy].
This article provides demonstrations and calculations, using rough-set theory and method, of the math-morphological features (MMFs), such as form parameter, lobation and sphericity, etc. drawn from 28 species of insects of the Hemiptera, Lepidoptera and Coleoptera based on their images. The results are compared with statistical analysis made by Zhao Hanqing, and also with the traditional classifications through the pattern recognition of neural network on the basis of the rough-set disposal. The result of the experiments showed that when used in categorical taxonomy, the importance of MMF was ranked from high to low: (roundness-likelihood. eccentricity) > (hot-hole number, sphericity, circularity) > (lobation, form parameter). The results of pattern recognition by neural network were completely identical with those of traditional classifications. Accordingly, the conclusion was that this theory applied in insect taxonomy was more idealistic compared with statistical analysis method, and it had great significance when used with rough-set neural network.


Mechanisms of ECG signs in chronic obstructive pulmonary disease.
Patients with chronic obstructive pulmonary disease (COPD) often have abnormal ECGs. Our aim was to separate the effects on ECG by airway obstruction, emphysema and right ventricular (RV) afterload in patients with COPD. A cross-sectional study was performed on 101 patients with COPD without left heart disease and 32 healthy age-matched controls. Body mass index (BMI) was measured, and pulmonary function tests, ECG, echocardiography and right heart catheterisation (only patients) were performed. Variables were grouped into (1) airway obstruction by FEV% (percentage of forced expiratory volume)_predicted, (2) emphysema by residual volume/total lung capacity and residual volume (percent of predicted) and (3) RV afterload by mean pulmonary pressure, artery compliance, vascular resistance and RV wall thickness. In multivariate regression analysis, emphysema correlated negatively to R+S amplitudes in horizontal and frontal leads, RV/left ventricle (LV) end-diastolic volume ratio to horizontal amplitudes and BMI negatively to frontal amplitudes. Increased airway obstruction, RV afterload and BMI correlated with horizontal QRS-axis clockwise rotation. Airway obstruction, RV afterload, RV/LV end-diastolic volume ratio and BMI correlated to the Sokolow-Lyon Index for RV, and RV afterload negatively to Sokolow-LyonIndex for LV. Several classical ECG changes could, however, not be ascribed to specific mechanisms. In COPD, the various pathophysiological mechanisms modify the ECG differently. Increased airway obstruction and RV afterload mainly increase the Sokolow-Lyon Index for RV mass and associate with clockwise rotation of the horizontal QRS-axis, whereas emphysema reduces the QRS amplitudes. BMI is an equally important determinant for the majority of the ECG changes.


Laparoscopic pyeloplasty for ureteropelvic junction obstruction: outcome of initial 12 procedures.
Open pyeloplasty has been the gold standard for surgical treatment of ureteropelvic junction (UPJ) obstruction, enjoying a long-term success rate exceeding 90%. Unfortunately, this procedure requires a muscle incision that entails some degree of morbidity. We have, therefore, investigated the feasibility of laparoscopic pyeloplasty for UPJ obstruction and report here the outcomes of our early cases. The median follow up is 25 months (range, 12-42 months). Between March 1999 and September 2001 we performed laparoscopic pyeloplasty on 12 ureters in 11 patients presenting with symptomatic hydronephrosis, secondary to a short stenosis of the UPJ or to ventrally crossing vessels; bilateral pyeloplasty was performed as a single procedure in one patient. We performed dismembered Anderson-Hynes pyeloplasty, Fenger plasty and Y-V plasty in eight, two and two ureters, respectively. All procedures were carried out transperitoneally. The procedure was completed successfully in all cases. Crossing vessels were noted in six of 12 ureters (50.0%). Mean operative time and blood loss in 11 patients (including one bilateral case) were 272.8 min (range, 175-480 min) and 96.4 mL (range, 20-340 mL), respectively. Postoperative complications were noted in two patients (18.2%): one instance of prolonged urine leakage and one anastomotic re-stricture. Eleven of 12 ureters (91.6%) demonstrated a patent UPJ on excretory urography and/or improvement of renal function on diuretic renography at a minimum follow up of 12 months. Although the procedure requires advanced laparoscopic skills, it can be safely and successfully completed as frequently as the conventional open procedure. Laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for UPJ obstruction.


Negative lateral shift of a light beam transmitted through a dielectric slab and interaction of boundary effects.
It is found that when a light beam travels through a slab of optically denser dielectric medium in air, the lateral shift of the transmitted beam can be negative. This is a novel phenomenon that is reversed in comparison with the geometrical optic prediction according to Snell's law of refraction. A Gaussian-shaped beam is analyzed in the paraxial approximation, and a comparison with numerical simulations is made. Finally, an explanation for the negativity of the lateral shift is suggested, in terms of the interaction of boundary effects of the slab's two interfaces with air.


IN VIVO AND IN VITRO ANTILEISHMANIAL EFFECTS OF METHANOLIC EXTRACT FROM BARK OF BURSERA APTERA.
Cutaneous leishmaniasis lacks effective and well-tolerated treatments. The current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy. Traditional medicine offers a complementary alternative for the treatment of various diseases. Additionally, several plants have shown success as anti-leishmanial agents. Therefore, we sought to evaluate the in vitro and in vivo activity of MEBA against Leishmania mexicana. Methanolic extract of B. aptera was obtained by macetration, after we determined in vitro anti-leishmanial activity of MEBA by MTT assay and the induced apoptosis in promastigotes by flow cytometry. To analyze the in vivo anti-leishmanial activity, we used infected mice that were treated and not treated with MEBA and we determined the levels of cytokines using ELISA. The phytochemical properties were determined by CG-MS and DPPH assay. We determined of LC50 of 0.408 mg/mL of MEBA for in vitro anti-leishmanial activity. MEBA induced apoptosis in promastigotes (15.3% ± 0.86). Treated mice exhibited smaller lesions and contained significantly fewer parasites than did untreated mice; in addition, we found that IFN-γ and TNF-α increased in the sera of MEBA-treated mice. GC-MS analysis showed that podophyllotoxin was the most abundant compound. Evaluation of the activity by DPPH assay demonstrated an SC50 of 11.72 μg/mL. Based on the above data, it was concluded that MEBA is a good candidate in the search for new anti-leishmanial agents.


A study of serum brain-derived neurotrophic factor level in individuals with obsessive compulsive disorder and their first-degree relatives as compared to the healthy population.
The nosological tradition in psychiatry defines diagnostic criteria for disorders based on expert consensus than objective biological markers reflecting underlying neurobiological correlates. Endophenotypes have been researched as heritable biological markers that can be quantified and defined to represent intermediate measures of a psychiatric illness. In obsessive-compulsive disorder (OCD), various putative biomarkers such as neuropsychological, neurophysiological, neuroradiological, brain-derived neurotrophic factor (BDNF), etc., have been explored. The study aimed to compare levels of serum BDNF in individuals with OCD and their unaffected first-degree relatives (FDR) with healthy controls (HC). This cross-sectional study compared serum BDNF levels in medication-free/naive individuals with OCD (n = 30) to their FDR (n = 30) and age-sex matched HC (n = 30). Intergroup comparison was done using analysis of variance (ANOVA) and post-hoc Tukey's test. Correlation analysis was conducted to find the relationship of sociodemographic and clinical correlates to serum BDNF as well as dimensional subtypes of OCD. No significant difference in BDNF levels was observed between OCD and HC (P = 0.13) but a significantly higher level was found in the FDR group compared to age-sex matched HC (P = 0.02). BDNF levels may have a complex interplay influencing the genetic inheritance and clinical manifestations of OCD. Further research is required before considering it a viable biomarker.


Medicaid Adult Dental Benefit Impact on Dental Utilization: A University Clinic Setting.
In 2014, the state of Colorado initiated new dental coverage benefits for adults in the Colorado Medicaid program. The goal of this study was to investigate the utilization and impact of this new dental coverage at the University of Colorado School of Dental Medicine. The utilization of dental services delivered and the numbers of patients in this program were compared before and after the implementation of the benefit. This retrospective study compared the utilization of services provided 2 years prior and 2 years after the Medicaid adult benefit was made available. Through the University of Colorado School of Dental Medicine (CU-SODM) electronic dental record, all adult Medicaid dental patients' (ages 21+) charts were extracted for zip code, CDT dental procedure codes, with a focus on tooth extraction compared to tooth saving procedures. Graphical analysis and Pearson's chi-squared tests were applied to assess the statistical significance of procedure utilization changes over time. After implementation of the Medicaid adult benefit, the number of patients seen at the school under this program increased by a factor of 4.5. The geographic range (zip code) increased with some patients coming from further distances to receive dental care. The number of patients from local zip codes increased by as much as 235%. There was a 51% increase in tooth saving procedures, which was statistically significant (P = 0.0013). Additionally, there was a 22% decrease in extractions, while not statistically significant (P = 0.0992), a downward trend was clear. The focus was on the utilization of Medicaid adult benefits at the dental school, which was only a small proportion of the state-wide Medicaid population. Therefore, these data are not generalizable for statewide assessments of the program. However, based on the findings at the school clinics, more adult patients utilized the benefits; and chose to receive more tooth saving procedures and less extractions after implementation of the Medicaid adult benefit. This Medicaid study conducted at the CU-SODM 2 years after the adult dental coverage can be used as a baseline for future studies.


Paricalcitol effects on activities and metabolism of platelet activating factor and on inflammatory cytokines in hemodialysis patients.
Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD). We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1β, IL-6, IL-8 and TNF-α were measured. Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1β, and TNF-α. These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1β and TNF-α circulating levels.


Association of breakfast styles such as Japanese, Western, and cereals with sleeping habits, eating habits, and lifestyle in preschool and elementary school children.
In Japan, breakfast styles are categorized into five groups; Japanese breakfast (JB; rice and miso soup), Western breakfast (WB; bread and milk), Japanese-Western breakfast (J-WB; alternative daily serving), cereal breakfast (CB), and breakfast skipping. In our recent studies, breakfast style was highly associated with the daily sleep-wake phase (chronotype), and healthy eating habits. In contrast with other breakfast style consumers, JB-consumers were positively associated with the morning chronotype and healthy eating habits such as a high consumption of a variety of protein sources, vegetables, and dietary fibers, and low consumption of sweetened juices. These previous studies included only adult participants; hence, in the current study, we investigated whether similar observations can be made in children. Preschool (aged 3-5 years) and elementary school children (6-8 years) (N = 6,104, 49.87% boys, 50.13% girls, mean body mass index 15.39 ± 0.03 kg/m2 for preschoolers and percentage of overweight -2.73 ± 0.22 for elementary school children) participated in this cross-sectional online survey on lifestyle, including eating and sleep habits, through their mother's responses. The results showed that the morning-evening type index values (chronotype indicator, smaller indicates morning type) were negatively correlated with JB intake (-0.05, p < 0.01) and positively correlated with WB (0.03, p < 0.05) and CB intake (0.06, p < 0.01), suggesting that the JB group exhibited the morning chronotype and the WB and CB groups exhibited the evening chronotype. The JB group consumed a variety of protein sources (mean ± SE; days/week) with more frequency (fish 2.95 ± 0.038 p < 0.001, soy 3.55 ± 0.043 p < 0.001, egg 3.82 ± 0.044 p < 0.001) compared with the WB group (fish 2.58 ± 0.033, soy 3.00 ± 0.038, egg 3.49 ± 0.039). On the other hand, the JB group consumed snacks (5.48 ± 0.042 p < 0.001) and sweetened juice (2.50 ± 0.050 p < 0.001) less frequently than the WB group (snacks; 5.80 ± 0.037 and sweetened juice; 2.74 ± 0.049). JB-eating children with a morning chronotype exhibited better sleep and eating habits than WB-eating children with an evening type pattern. The results suggest that JB eating habits may be associated with good eating and sleeping lifestyles, even among preschool and elementary school children.


Renchangianins F and G: two new sesquiterpenoids from Kadsura renchangiana.
Phytochemical investigation on the stems of Kadsura renchangiana led to the isolation of two new sesquiterpenoids, renchangianins F and G (1 and 2). Their structures were elucidated by spectroscopic methods, including 2D NMR techniques. The in vitro cytotoxic activities of the isolates were studied against HepG2, A549, and LN229 cancer cell lines.


Butandioldehydrogenase in Vibrio parahaemolyticus.
396 strains of V. parahaemolyticus, 345 originating from Togo and 51 from Japan, were submitted to the study of butandiol dehydrogenase (BDH). It was found that 52.3% of the strains were BDH-positive and 44.2% BDH-negative. An intermediate group characterized by weak reactions amounted to 3.5% of the strains. The distribution of this enzyme parallels to a certain degree the results of serotyping. Positive reactions have been found in all or most strains belonging to serotypes 03K29, O4K8, 04K12, 04K55, 05K15, and 012K19, whereas strains of serotypes 03K5 and 04K10 gave negative reactions. In serotype 05K17 both properties were found in nearly equal proportions. The test of BDH, which can supplement serotyping in characterizing strains of V. parahaemolyticus, can be applied as an aid to epidemiological studies.


Self-assembly of heterogeneous supramolecular structures with uniaxial anisotropy.
Uniaxial anisotropy in two-dimensional self-assembled supramolecular structures is achieved by the coadsorption of two different linear molecules with complementary amine and imide functionalization. The two-dimensional monolayer is defined by a one-dimensional stack of binary chains, which can be forced to line up along steps in vicinal surfaces. The competing driving forces in the self-organization process are discussed in light of the structures observed during single molecule adsorption and coadsorption on flat and vicinal surfaces and the corresponding theoretical calculations.


Behavior Change Following Pain Neuroscience Education in Middle Schools: A Public Health Trial.
Chronic pain and the opioid epidemic need early, upstream interventions to aim at meaningful downstream behavioral changes. A recent pain neuroscience education (PNE) program was developed and tested for middle-school students to increase pain knowledge and promote healthier beliefs regarding pain. In this study, 668 seventh-grade middle-school students either received a PNE lecture (n = 220); usual curriculum school pain education (UC) (n = 198) or PNE followed by two booster (PNEBoost) sessions (n = 250). Prior to, immediately after and at six-month follow-up, pain knowledge and fear of physical activity was measured. Six months after the initial intervention school, physical education, recess and sports attendance/participation as well as healthcare choices for pain (doctor visits, rehabilitation visits and pain medication use) were measured. Students receiving PNEBoost used 30.6% less pain medication in the last 6 months compared to UC (p = 0.024). PNEBoost was superior to PNE for rehabilitation visits in students experiencing pain (p = 0.01) and UC for attending school in students who have experienced pain > 3 months (p = 0.004). In conclusion, PNEBoost yielded more positive behavioral results in middle school children at six-month follow-up than PNE and UC, including significant reduction in pain medication use.


The Erector Spinae Plane Block Provides Visceral Abdominal Analgesia in Bariatric Surgery: A Report of 3 Cases.
Postoperative pain after bariatric surgery can be significant and yet difficult to manage. These patients frequently have associated obstructive sleep apnea and are at risk of respiratory depression with opioid analgesia. Abdominal wall blocks such as the subcostal transversus abdominis plane block are not of significant benefit, probably in part because they provide only somatic analgesia. The ultrasound-guided erector spinae plane (ESP) block is a recently described regional anesthetic technique for providing thoracic analgesia when performed at the level of the T5 transverse process. Local anesthetic injected into the fascial plane deep to the erector spinae muscle spreads in a craniocaudal fashion over several levels. Local anesthetic also penetrates anteriorly through the intertransverse connective tissue and enters the thoracic paravertebral space where it can potentially block not only the ventral and dorsal rami of spinal nerves but also the rami communicantes that transmit sympathetic fibers. Coupled with the fact that the erector spinae muscle and ESP extend down to the lumbar spine, this suggests that the ESP block could result in both visceral and somatic abdominal analgesia if the injection were performed at a lower thoracic level. We describe a series of 3 cases that illustrate the efficacy of bilateral ESP blocks performed at the level of the T7 transverse process for relieving visceral abdominal pain following bariatric surgery. Further investigation is recommended to establish the potential of the ESP block as an analgesic modality in abdominal surgery.


From Linear to Nets: Multiconfiguration Polymer Structure Generation with PolyFlin.
Molecular modeling and simulations are essential tools in polymer science and engineering, enabling researchers to predict and understand the properties of macromolecules, including their structure, dynamics, thermodynamics, and overall material characteristics. However, one of the key challenges in polymer simulation and modeling lies in the initial topology design, as existing programs often lack the capability to generate all types of polymer forms. In this study, we present PolyFlin, a powerful Python module that addresses this limitation by allowing the generation of a wide range of polymer structures, from simple homopolymers to complex copolymers, including grafts, cyclic, star, dendrimers, and nets. PolyFlin offers a versatile and efficient tool for exploring and creating diverse polymer architectures, facilitating advancements in various fields that require precise polymer modeling and simulation.


Association of cord blood chemokines and other biomarkers with neonatal complications following intrauterine inflammation.
Intrauterine inflammation has been associated with preterm birth and neonatal complications. Few reports have comprehensively investigated multiple cytokine profiles in cord blood and precisely identified surrogate markers for intrauterine inflammation. To identify the cytokines and surrogate markers associated with intrauterine inflammation and subsequent neonatal complications. We analyzed cord blood samples from 135 patients admitted to the neonatal intensive care unit at Sasebo City General Hospital. We retrospectively determined the associations between the presence of neonatal complications and cord blood cytokines, prenatal factors, and laboratory data at birth. A total of 27 cytokines in the cord blood were measured using a bead-based array sandwich immunoassay. Both Th1 and Th2 cytokine levels were low, whereas the levels of growth factors and chemokines were high. In particular, chemokines IL-8, MCP-1, and MIP-1α were significantly higher in very premature neonates when compared with more mature neonates. In addition, some have been shown to be associated with multiple neonatal complications, including patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Similarly, the levels of N-terminal pro-brain natriuretic peptide, nucleated RBC, and urinary β2-microglobulin were associated with these complications and chemokine levels. Our results suggest the association of inflammatory chemokines IL-8, MCP-1, and MIP-1α with intrauterine inflammation, premature birth, and neonatal complications in these perinatal subjects. Furthermore, the association of the aforementioned biomarkers with PDA, RDS, and CLD may help establish early diagnostic measures to predict such neonatal complications following intrauterine inflammation.


Further validation of the interpersonal exchange model of sexual satisfaction.
We conducted two studies to further test the validity of the Interpersonal Exchange Model of Sexual Satisfaction for long-term opposite-sex relationships (IEMSS; Lawrance & Byers, 1995). Study 1 examined, in a sample of 79 individuals, the extent to which the history of sexual exchanges is associated with sexual satisfaction as well as whether changes in sexual rewards and costs are associated with change in sexual satisfaction. Using a sample of 104 couples, Study 2 examined whether partner rewards and costs add to individuals' own sexual satisfaction over and above own sexual rewards and costs for men or women. The results provided further evidence for the validity of the IEMSS, including support for the propositions that in long-term relationships: (a) sexual satisfaction is influenced by the history of sexual rewards and costs rather than by rewards and costs at a particular point in time; (b) decreases in sexual satisfaction are associated with sexual exchanges becoming less favorable; and (c) satisfaction is influenced by dyadic factors for both men and women.


Dynamical scaling and the finite-capacity anomaly in three-wave turbulence.
We present a systematic study of the dynamical scaling process leading to the establishment of the Kolmogorov-Zakharov (KZ) spectrum in weak three-wave turbulence. In the finite-capacity case, in which the transient spectrum reaches infinite frequency in finite time, the dynamical scaling exponent is anomalous in the sense that it cannot be determined from dimensional considerations. As a consequence, the transient spectrum preceding the establishment of the steady state is steeper than the KZ spectrum. Constant energy flux is actually established from right to left in frequency space after the singularity of the transient solution. From arguments based on entropy production, a steeper transient spectrum is heuristically plausible.


[Peroneal tendoscopy: our experience].
The peroneal tendon pathology is a common cause of posterolateral ankle pain. Recently, the incidence and awareness of this disease and its treatment are booming thanks to the development of tendoscopic procedures. To describe and assess the current role and indications of tendoscopy for peroneal tendon pathology. From June 2010 to July 2011, twenty three patients with retrofibular pain were treated with peroneal tendoscopy. We founded twelve peroneal brevis tendon tears, six peroneal longus tendon tears, three cases of tenosynovitis and two cases of luxation, one patient with an intrasheath subluxation and another one of extrasheath. Of the 23 patients, 12 had another injury associated: 4 talar osteochondral lesions, 3 instabilities and 7 cases of soft tissue impingement. The three main indications include tendon tears, tenosynovitis and subluxation or luxation. It is a technically demanding procedure that requires extensive experience in arthroscopic management of small joints and can be particularly complex in cases of wide tenosynovitis, broad tendon tears or anatomical defects but very useful for the evaluation of the lesions and for the treatment of peroneal tendon disorders. Tendoscopy is a useful procedure with low morbidity and excellent functional results to treat the pathology of the peroneal tendons.


Long-term outcome of iontophoresis treatment for torticollis.
In 1969, a patient with torticollis was successfully treated by a procedure called iontophoresis. Between 1958 and 1972 223 patients with torticollis were treated with this procedure. 88 of these patients (39%) were located and 56 (25% of the total, 64% of those located) returned a survey regarding their condition. 28 (13% of the total, 32% of those located, 50% of those responding) enjoyed an initial period of improvement. Of these, 16 patients (7% of the total, 18% of those located, 29% of those responding, 51% of those with initial improvement) reported sustained improvement through the time of the survey. However, 5 of these patients had additional treatment with botulinum toxin or selective denervation. We conclude that the long term effectiveness of iontophoresis treatment in the course of torticollis is minimal.


Commentary on "Multi-Component Care Bundle in Geriatric Fracture Hip for Reducing Postoperative Delirium".
The letter to the editor suggested several questions regarding the methodology of the recent article by Lam et al who determined effect of multicomponent care bundle on the development of postoperative delirium. This article is published in Geriatric Orthopaedic Surgery & Rehabilitation . 2021; 12:21514593211004530. Our concerns included the incomplete preoperative assessment, possible influences of anaesthetic and intraoperative managements on the development of postoperative delirium, bias effect of postoperative analgesia on the primary and secondary findings, and real clinical value of multicomponent care bundle to decrease the risk of postoperative delirium. We believe that clarifying these issues would improve the transparency of this study and interpretation of findings.


[A case of neuroendocrine carcinoma of the anal canal with multiple bone metastases successfully treated with combined modality therapy].
Neuroendocrine carcinoma (NEC) of the anal canal is a comparatively rare tumor with a poor prognosis. We report herein a case of NEC of the anal canal with multiple bone metastases that was successfully treated with combined therapy. A 63-year-old man was referred to our hospital with the chief complaint of anal and back pain. A tumor was found in the anal canal, and pathologic examination revealed it to be NEC( Ki-67 expression>50%); fluorodeoxyglucose( FDG) positron emission tomography (PET)-computed tomography (CT) showed multiple bone metastases. Initially, a l-leucovorin/5- fluorouraci(l 5-FU)/oxaliplatin( L-OHP)(: mFOLFOX6)/bevacizumab( Bmab) regimen and octreotide were administered to treat the unresectable and advanced NEC. Strontium-89 and zoledronate were used to treat pain related to the bone metastases. After 3 months, the tumor and bone metastases became difficult to identify. The patient experienced grade 2 neurotoxicity after 5 months, and thus, we stopped L-OHP administration. After 10 months, we reintroduced L-OHP because of additional progression of the bone metastases.


Effect of taxifolin on methanol-induced oxidative and inflammatory optic nerve damage in rats.
Purpose: Oxidative stress and inflammation have been demonstrated in the pathogenesis of methanol toxicity. Taxifolin has antioxidant and anti-inflammatory properties. In this study, we examined the protective effect of taxifolin against methanol-induced optic nerve toxicity. Materials and methods: Animals were divided into four groups (n = 6): healthy control group (HG), methotrexate (MTX) treated group, methotrexate + methanol treated group (MTX + M), and methotrexate + methanol + taxifolin treated group (MTX + M+T). MTX was administered to all groups except HG group 3 mg/kg via oral gavage for 7 d. After that 20% methanol was orally administered to the MTX + M and MTX + M+T group at a dose of 3 g/kg. After 4 h, taxifolin was orally administered to MTX + M+T group 50 mg/kg. Animals were sacrificed by high-dose thiopental anaesthesia, 8 h after taxifolin administration and biochemical studies were performed. Results: Malondialdehyde (MDA), total oxidant system, nuclear factor kappa B (NF-κB), and tumour necrosis factor-alpha levels were significantly higher in the optic nerve of MTX and MTX + M groups compared to HG group. Otherwise, total glutathione (tGSH) and total antioxidant system levels decreased in MTX and MTX + M groups according to the HG group. MDA, total oxidant system, NF-κB, and tumour necrosis factor-alpha levels were decreased in the MTX + M+T group and tGSH, and total antioxidant system levels increased in the MTX + M+T group according to the MTX + M group. Conclusions: These results indicate that taxifolin prevents oxidative and inflammatory optic nerve damage due to methanol exposure.


Phage on the stage.
The resurgence of interest in bacteriophages for use in combating antibiotic resistant bacteria is coincident with an urgent call for more effective science education practices, including hands-on learning opportunities. To address this issue, a number of solutions have been proposed, including a large educational experiment, begun in 2007 by the Howard Hughes Medical Institute and currently involving over 85 colleges and universities, which has students discovering unique phages, obtaining images, and purifying phage DNA. A subset of these phage genomes is sequenced and analyzed using bioinformatics tools. Papers describing individual phage discoveries and comparative genomic studies are being published regularly. The vast majority of students in the program are in their first year of college, a critical time in capturing their interest and retaining them as science majors. This viral discovery model is being adopted and modified by a wide variety of educational institutions using a number of different bacterial hosts. In the opinion of the authors, this program and others like it represent a model accessible to virtually any undergraduate setting. And because of these programs, bacteriophage enthusiasts (academics, health professionals, biotechnology companies) can look forward to more well prepared students entering their ranks and should anticipate many more potentially useful phages discovered and characterized.


Epithelial-mesenchymal transition in morphogenesis, cancer progression and angiogenesis.
All organs consist of an epithelium and an associated mesenchyme, so these epithelial-mesenchymal intercations are among the most important phenomena in nature. The aim of this article is the summarize the common mechanisms involved in the establishment of epithelial mesenchymal transition in three biological processes, namely organogenesis, tumor progression and metastasis, and angiogenesis, apparently independent each from other. A common feature of these processes is the fact that specialized epithelial cells lose their features, including cell adhesion and polarity, reorganize their cytoskeleton, and acquire a mesenchymal morphology and the ability to migrate.


Turbulent magnetic diffusivity tensor for time-dependent mean fields.
We reexamine the nature of the turbulent magnetic diffusivity tensor of mean field electrodynamics and show that the predicted growth rate of the mean field is, in general, incorrect if the tensor is calculated via consideration of time-independent mean magnetic fields. We describe how the traditional expansion procedure for the mean electromotive force should be extended to include time derivatives of the mean magnetic field, and illustrate the consistency of this approach by means of a perturbation analysis for a mean field varying on long spatial scales. Finally, we examine the magnitude of this new contribution to the magnetic diffusion for a particular flow.


Endograft collapse after thoracic endovascular aortic repair.
To provide insight into the causes, timing, and optimal management of endograft collapse after thoracic endovascular aortic repair (TEVAR). A comprehensive review was conducted of all published cases of endograft collapse after TEVAR identified using Medline, Cochrane Library Central, and EMBASE. In total, 32 articles describing 60 patients (45 men; mean age 40.6 ± 17.2 years, range 17-78) with endograft collapse were included. All data were extracted from the articles and systematically entered into a database for meta-analysis. In the 60 cases of endograft collapse, TEVAR had most commonly been applied to repair traumatic thoracic aortic injuries (39, 65%), followed by acute and chronic type B aortic dissections (9, 15%). The median time interval between TEVAR and diagnosis of endograft collapse was 15 days (range 1 day to 79 months). On average, the collapsed endografts were oversized by 26.7% ± 12.0% (range 8.3%-60.0%). Excessive oversizing was reported as the primary cause of endograft collapse in 20%, and a small radius of curvature of the aortic arch was responsible for 48% of the cases. The 30-day mortality was 8.3%, and the freedom from procedure-related death at 3 years after diagnosis of stent-graft collapse was 83.1% for asymptomatic patients compared with 72.7% for patients who had symptoms at diagnosis (p=0.029). Endograft collapse typically occurs shortly after TEVAR, most frequently after endovascular repair of traumatic aortic injury. A high level of suspicion for endograft collapse in the first month after TEVAR, as well as further improvement of current endovascular devices, may be required to improve the long-term outcomes of patients after TEVAR.


Lactate and adenosine triphosphate in the extender enhance the cryosurvival of rat epididymal sperm.
We evaluated the cryosurvival of rat epididymal sperm preserved in raffinose-modified Krebs-Ringer bicarbonate-egg yolk extender supplemented with various energy-yielding substrates (glucose, pyruvate, lactate, and ATP) and assessed the effect on sperm oxygen consumption. The incubation of sperm at 37 degrees C for 10 min in lactate-free extender decreased sperm motility and oxygen consumption before and after thawing compared with those of sperm in glucose- and pyruvate-free mediums. We then focused on the effect of supplementing the extender with lactate (0, 10.79, 21.58, 32.37, and 43.16 mM) and found that sperm frozen and thawed in extender supplemented with 32.37 mM lactate exhibited the highest motility. When we supplemented extender containing 32.37 mM lactate with ATP (0, 0.92, 1.85, 3.70, and 5.55 mM), sperm frozen and thawed in the extender supplemented with 1.85 mM ATP exhibited considerably higher motility and viability than those of sperm frozen and thawed in ATP-free extender. These results provide the first evidence that supplementation of the raffinose-modified Krebs-Ringer bicarbonate-egg yolk extender with 32.37 mM lactate and 1.85 mM ATP increases of number of motile sperm before freezing and enhances the cryosurvival of rat sperm. These supplements to the extender may enhance sperm cryosurvival by improving the metabolic capacity of sperm before freezing.


Teamworking post-polio.
People with post-polio syndrome are used to getting on with their lives, but healthcare staff can identify their needs by careful assessment.


Opioid-induced respiratory depression: a mathematical model for fentanyl.
In this paper, respiratory depressant effects of fentanyl are described quantitatively by a mathematical model. The model is an extension of a previous one, which reproduces the human ventilatory control system on a physiological basis. It includes the following: three compartments for gas storage and exchange (lungs, body tissue, and brain tissue); the main mechanisms involved in ventilation control (peripheral chemoreceptors, central chemoreceptors, and the central hypoxic depression); and local blood flow regulation. The effects of fentanyl on the respiratory system include a decrease in peripheral and central chemoreceptor gains on ventilation and a direct inhibition of respiratory neural activity. All parameters in the model were chosen according to the literature. The model is able to reproduce the ventilatory effects of fentanyl in several conditions: 1) constant levels of fentanyl; 2) after a bolus injection; 3) at fixed levels of P(ETCO2); and 4) after artificial ventilation. According to the model, in spontaneously breathing subjects, minute ventilation depends on two opposing actions: fentanyl inhibitory influences, which depress ventilation, reducing oxygen tension and increasing CO2 tension, and the consequent activation of chemoreceptors, which stimulates ventilation. Simulations of anesthetized patients resuming spontaneous breathing after artificial ventilation demonstrate the risk of prolonged apnea and tissue hypoxemia. A safe transition can be achieved by increasing patient PCO2 toward the end of artificial ventilation, because an advanced chemoreceptor stimulation is produced, which promptly counteracts fentanyl-induced inhibition at cessation of artificial ventilation.


Direct Effects of Physcion, Chrysophanol, Emodin, and Pachybasin on Germination and Appressorium Formation of the Barley ( Hordeum vulgare L.) Powdery Mildew Fungus Blumeria graminis f. sp. hordei (DC.) Speer.
Several anthraquinone derivatives are active components of fungicidal formulations particularly effective against powdery mildew fungi. The antimildew effect of compounds such as physcion and chrysophanol is largely attributed to host plant defense induction. However, so far a direct fungistatic/fungicidal effect of anthraquinone derivatives on powdery mildew fungi has not been unequivocally demonstrated. By applying a Formvar-based in vitro system we demonstrate a direct, dose-dependent effect of physcion, chrysophanol, emodin, and pachybasin on conidial germination and appressorium formation of Blumeria graminis f. sp. hordei (DC.) Speer, the causative agent of barley ( Hordeum vulgare L.) powdery mildew. Physcion was the most effective among the tested compounds. At higher doses, physcion mainly inhibited conidial germination. At lower rates, however, a distinct interference with appressorium formation became discernible. Physcion and others may act by modulating both the infection capacity of the powdery mildew pathogen and host plant defense. Our results suggest a specific arrangement of substituents at the anthraquinone backbone structure being crucial for the direct antimildew effect.


Raman spectroscopy of boron-doped single-layer graphene.
The introduction of foreign atoms, such as nitrogen, into the hexagonal network of an sp(2)-hybridized carbon atom monolayer has been demonstrated and constitutes an effective tool for tailoring the intrinsic properties of graphene. Here, we report that boron atoms can be efficiently substituted for carbon in graphene. Single-layer graphene substitutionally doped with boron was prepared by the mechanical exfoliation of boron-doped graphite. X-ray photoelectron spectroscopy demonstrated that the amount of substitutional boron in graphite was ~0.22 atom %. Raman spectroscopy demonstrated that the boron atoms were spaced 4.76 nm apart in single-layer graphene. The 7-fold higher intensity of the D-band when compared to the G-band was explained by the elastically scattered photoexcited electrons by boron atoms before emitting a phonon. The frequency of the G-band in single-layer substitutionally boron-doped graphene was unchanged, which could be explained by the p-type boron doping (stiffening) counteracting the tensile strain effect of the larger carbon-boron bond length (softening). Boron-doped graphene appears to be a useful tool for engineering the physical and chemical properties of graphene.


[The structure and incidence of the basic causes of maternal mortality].
The author treats by the presented scientific publication the structure and frequency of causes for maternal mortality in particular countries and mainly in Bulgaria. Several structure types of maternal mortality are examined--"extragenital", "hemorrhagic", "septic". It has been proven through a close examination of the work of women's consultation cabinets with regard to maternal mortality that a considerable dependence and regularity is determined due to the insufficient coverage of women from housing complexes (only 24.9% have 6-14 visits). For 1995 dead pregnant women, women in delivery and young mothers in particular regions are 0.1 for 1000 from 73,032 checked-up women. Only in Sofia and Montana region the mortality rate is 0.2 for 1000. For 1996 the mortality rate in the presented regions (see Table N1) for pregnant women, women in delivery and young mothers has increases to 7 (0.2 for 1000).


Action spectra for inactivation of dry phage T1 after monochromatic (150-254 nm) synchrotron irradiation in the presence and absence of photoreactivation and dark repair.
Dry phage T1 was irradiated with monochromatic uv radiation (150-254 nm) in vacuo. The inactivation sensitivity was highest at 150 nm. On Escherichia coli Bs-1, the phage inactivation sensitivity was two and four times higher at 150 nm than at 254 and 230 nm, respectively. Action spectra for phage inactivation on both E. coli B and Bs-1 fit the absorption spectrum of phage DNA, except around 190 nm. The host-cell- reactivable fraction for vacuum-uv radiation (below 190 nm) was smaller than that with far-uv radiation. There was almost no photoreactivation at 150 nm, in contrast to a photoreactivation sector of about 0.3 at 254 nm.


A high-throughput screening strategy for detecting CRISPR-Cas9 induced mutations using next-generation sequencing.
CRISPR-Cas9 is a revolutionary genome editing technique that allows for efficient and directed alterations of the eukaryotic genome. This relatively new technology has already been used in a large number of 'loss of function' experiments in cultured cells. Despite its simplicity and efficiency, screening for mutated clones remains time-consuming, laborious and/or expensive. Here we report a high-throughput screening strategy that allows parallel screening of up to 96 clones, using next-generation sequencing. As a proof of principle, we used CRISPR-Cas9 to disrupt the coding sequence of the homeobox gene, Evx1 in mouse embryonic stem cells. We screened 67 CRISPR-Cas9 transfected clones simultaneously by next-generation sequencing on the Ion Torrent PGM. We were able to identify both homozygous and heterozygous Evx1 mutants, as well as mixed clones, which must be identified to maintain the integrity of subsequent experiments. Our CRISPR-Cas9 screening strategy could be widely applied to screen for CRISPR-Cas9 mutants in a variety of contexts including the generation of mutant cell lines for in vitro research, the generation of transgenic organisms and for assessing the veracity of CRISPR-Cas9 homology directed repair. This technique is cost and time-effective, provides information on clonal heterogeneity and is adaptable for use on various sequencing platforms.


Very early combination antiretroviral therapy in infants: prospects for cure.
A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infected child (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs. The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia. This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.


Carbonic anhydrase XIV: luminal expression suggests key role in renal acidification.
Carbonic anhydrase (CA) plays a fundamental role in regulation of systemic acid-base homeostasis by facilitating urinary acidification. Four CA isozymes (CA II, IV, XII, XIV) have been identified in kidney. Until now, luminal CA IV, a GPI-anchored isozyme, was thought to mediate most bicarbonate absorption. Although CA XIV mRNA has been demonstrated in mouse and human kidney, the localization of this newly discovered CA has not been established. RT-PCR and Western blot analyses were used to demonstrate CA XIV mRNA and protein in extracts of cortex and medulla of mouse kidney. Polyclonal antibodies against mouse CA XIV were utilized for immunofluorescence to examine the pattern of expression of CA XIV in the nephron of both rat and mouse kidney. Immunofluorescence staining showed abundant expression of CA XIV in apical plasma membranes of the S1 and S2 segments of proximal tubules, and weaker staining in the basolateral membranes. Also, strong staining was seen in the initial portion of the thin descending limb of Henle. These results show that luminal CA XIV is strongly expressed in regions of the rodent nephron that have been thought to be important in urinary acidification. Staining for CA XIV and CA IV in the same sections showed some areas of co-expression, but also some areas where each was expressed without the other. Luminal CA XIV may account for a substantial fraction of the bicarbonate reabsorption previously attributed to CA IV. If so, CA XIV and CA IV may be functionally redundant.


Free-Standing Holey Ni(OH)2 Nanosheets with Enhanced Activity for Water Oxidation.
Electrochemical water oxidation is the key technology in water-splitting reactions and rechargeable metal-air batteries, which is very attractive for renewable energy conversion and storage. Replacement of precious catalysts with cost-effective and highly active alternatives is still a great challenge. Herein, based on theoretical predictions, holey structures are designed and fabricated on the free-standing conventional 2D OER catalyst. By well-controlled defects engineering, uniform tiny holes are created on the free-standing Ni(OH)2 nanosheets via a sol-gel method, with the embedded Zn components as the template for holes production. The whole preparation process is feasible and effective to make full use of the basal plane of 2D nanomaterials, which can provide higher surface area, richer defects, more grain boundaries, and edge sites, as well as greater distorted surfaces. Meanwhile, these holes developed inside the sheet structure can supply tremendous permeable channels for ions adsorption and transportation, enable a fast interfacial charge transfer and accelerate the reaction process. The as-prepared 2D holey Ni(OH)2 nanostructures exhibit excellent catalytic performance toward electrochemical water oxidation, with lower onset overpotentials and higher current densities compared with the pristine Ni(OH)2 catalyst, suggesting the holey defects engineering is a promising strategy for efficient water-splitting devices and rechargeable metal-air batteries.