Natural and biocompatible dressing unit based on tea carbon dots modified core-shell electrospun fiber for diabetic wound disinfection and healing.
Wound infection and healing in patients with diabetes is one of the complex problems in trauma treatment. Therefore, designing and preparing an advanced dressing membrane for treating the wounds of such patients is essential. In this study, a zein film with biological tea carbon dots (TCDs) and calcium peroxide (CaO2) as the main components for promoting diabetic wound healing was prepared by an electrospinning technique, which combines the advantages of natural degradability and biosafety. CaO2 is a biocompatible material with a microsphere structure that reacts with water to release hydrogen peroxide and calcium ions. TCDs with a small diameter were doped in the membrane to mitigate its properties while improving the antibacterial and healing effects of the membrane. TCDs/CaO2 was mixed with ethyl cellulose-modified zein (ZE) to prepare the dressing membrane. The antibacterial properties, biocompatibility and wound-healing properties of the composite membrane were investigated by antibacterial experiment, cell experiment and a full-thickness skin defect. TCDs/CaO2 @ZE exhibited significant anti-inflammatory and wound healing-promoting properties in diabetic rats, without any cytotoxicity. This study is meaningful in developing a natural and biocompatible dressing membrane for diabetic wound healing, which shows a promising application in wound disinfection and recovery in patients with chronic diseases.


Primary Intraosseous Lymphoplasmacyte-Rich Meningioma.
Lymphoplasmacyte-rich meningioma is an uncommon variant of meningioma, and that arising in the extradural site is extremely rare. We report a case of primary intraosseous lymphoplasmacyte-rich meningioma. A 51-year-old woman presented with left frontal scalp swelling lasting longer than 1 year. Magnetic resonance imaging revealed an intraosseous extradural mass in the left frontal region with bone destruction. Surgical resection of the mass with a cranioplasty was performed. The postoperative course was uneventful, and histopathologic findings were consistent with a lymphoplasmacyte-rich meningioma. After a follow-up period of 2 years, no residual tumor or in situ recurrence was noted. Lymphoplasmacyte-rich meningioma occurring in the intraosseous extradural region is extremely rare. It is crucial for clinicians to be aware of this entity as it can be easily mistaken for more common osteogenic neoplasms occurring at this site.


Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity.
Obesity is associated with the development of leptin resistance. However, the effects of leptin resistance on leptin-regulated metabolic processes and the biochemical defects that cause leptin resistance are poorly understood. We have addressed in rats the effect of dietinduced obesity (DIO), a situation of elevated tissue lipid levels, on the well described lipid-lowering effect of leptin in liver, an action that is proposed to be important for the prevention of tissue lipotoxicity and insulin resistance. In addition, we have addressed the role of phosphatidylinositol 3-kinase (PI 3-kinase) in mediating the acute effects of leptin on hepatic lipid levels in lean and DIO animals. A 90-min leptin ( approximately 10 ng/ml) perfusion of isolated livers from lean animals decreased triglyceride levels by 42 +/- 5% (p = 0.006). However, leptin concentrations ranging from approximately 10 to approximately 90 ng/ml had no effect on triglyceride levels in livers from DIO animals. The acute lipid-lowering effect of leptin on livers from lean animals was mediated by a PI 3-kinase-dependent mechanism, because wortmannin and LY294002, the PI 3-kinase inhibitors, blocked the effects of leptin on hepatic triglyceride levels and leptin increased liver PI 3-kinase activity by 183 +/- 6% (p = 0.003) and insulin receptor substrate 1 tyrosine phosphorylation by 185 +/- 30% (p = 0.02) in the absence of PI 3-kinase inhibitors. Contrary to the effects of leptin in lean livers, leptin did not activate PI 3-kinase in livers from DIO rats. These data present evidence for a role for 1). leptin resistance in contributing to the excessive accumulation of tissue lipid in obesity, 2). PI 3-kinase in mediating the acute lipid-lowering effects of leptin in liver, and 3). defective leptin activation of PI 3-kinase as a novel mechanism of leptin resistance.


Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the B cell receptor by regulating calcium and calmodulin.
B cells signal through both the B cell receptor (BCR) which binds antigens and Toll-like receptors (TLRs) including TLR9 which recognises CpG DNA. Activation of TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase (BTK) is required for synergistic IL6 production and up-regulation of surface expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells. We show that BTK is essential for co-localisation of the BCR and TLR9 within a potential auto-phagosome-like compartment in the Namalwa human B cell line. Downstream of BTK we find that calcium acting via calmodulin is required for this process. These data provide new insights into the role of BTK, an important target for autoimmune diseases, in B cell activation.


A comparison of three methods to determine the subject matter in textual data.
This study compares three different methods commonly employed for the determination and interpretation of the subject matter of large corpuses of textual data. The methods reviewed are: (1) topic modeling, (2) community or group detection, and (3) cluster analysis of semantic networks. Two different datasets related to health topics were gathered from Twitter posts to compare the methods. The first dataset includes 16,138 original tweets concerning HIV pre-exposure prophylaxis (PrEP) from April 3, 2019 to April 3, 2020. The second dataset is comprised of 12,613 tweets about childhood vaccination from July 1, 2018 to October 15, 2018. Our findings suggest that the separate "topics" suggested by semantic networks (community detection) and/or cluster analysis (Ward's method) are more clearly identified than the topic modeling results. Topic modeling produced more subjects, but these tended to overlap. This study offers a better understanding of how results may vary based on method to determine subject matter chosen.


Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate.
The colonial ascidian Botryllus schlosseri continuously regenerates entire bodies in an asexual budding process. The germ line of the newly developing bodies is derived from migrating germ cell precursors, but the signals governing this homing process are unknown. Here we show that germ cell precursors can be prospectively isolated based on expression of aldehyde dehydrogenase and integrin alpha-6, and that these cells express germ cell markers such as vasa, pumilio and piwi, as well as sphingosine-1-phosphate receptor. In vitro, sphingosine-1-phosphate (S1P) stimulates migration of germ cells, which depends on integrin alpha-6 activity. In vivo, S1P signalling is essential for homing of germ cells to newly developing bodies. S1P is generated by sphingosine kinase in the developing germ cell niche and degraded by lipid phosphate phosphatase in somatic tissues. These results demonstrate a previously unknown role of the S1P signalling pathway in germ cell migration in the ascidian Botryllus schlosseri.


Changes in the levels and phosphorylation status of Akt, AMPK, CREB and FoxO1 in hypothalamus of rainbow trout under conditions of enhanced glucosensing activity.
There is no available information about mechanisms linking glucosensing activation in fish and changes in the expression of brain neuropeptides controlling food intake. Therefore, we assessed in rainbow trout hypothalamus the effects of raised levels of glucose on the levels and phosphorylation status of two transcription factors, FoxO1 and CREB, possibly involved in linking these processes. We also aimed to assess the changes in the levels and phosphorylation status of two proteins possibly involved in the modulation of these transcription factors: Akt and AMPK. Therefore, in pooled preparations of hypothalamus incubated for 3 and 6 h in the presence of 2, 4 or 8 mmol l-1 d-glucose, we evaluated the response of parameters related to glucosensing mechanisms, neuropeptide expression and levels and phosphorylation status of the proteins of interest. The activation of hypothalamic glucosensing systems and the concomitant enhanced anorectic potential occurred in parallel with activation of Akt and inhibition of AMPK. The changes in these proteins relate to neuropeptide expression through changes in the level and phosphorylation status of transcription factors under their control, such as CREB and FoxO1, which displayed inhibitory (CREB) or activatory (FoxO1) responses to increased glucose.


Freestyle perforator flap in earlobe reconstruction.
In earlobe reconstruction, it is a challenging task to find a simple one-stage technique that is applicable to the variable configurations of defects and that results in a longstanding naturally appearing earlobe. In this article, we present a perforator-based flap design for earlobe reconstruction with preoperative perforator detection by pencil doppler to ensure the maximum vascularity of the used flap. Thirty cases of earlobe reconstruction were performed in the Department of Plastic and Reconstructive Surgery at Tanta University in the period from July 2015 to July 2019 using the technique described in this article. None of our cases developed necrosis of the flaps. The mean result for the aesthetic evaluation of our cases was 4.7 and the mean patient satisfaction was 4.8 where the maximum score was 5. freestyle perforator flap with preoperative doppler perforator detection is a safe and reliable method of earlobe reconstruction.


Link between characteristics of Fe(III) oxides and critical role in enhancing anaerobic methanogenic degradation of complex organic compounds.
Fe(III) oxides have been investigated to accelerate anaerobic methanogenic degradation of complex organic compounds. However, the critical role linked to the characteristics of different types of Fe(III) oxides is still unclear. Study presented here performed a side-by-side comparison of four types of Fe(III) oxides including Fe(III)-citrate, ferrihydrite, hematite and magnetite to evaluate their effectiveness in methanogenic degradation of phenol. Results showed that, amorphous Fe(III)-citrate group showed the fastest phenol degradation and Fe2+ release among all the groups, followed by poorly crystalline ferrihydrite. Although Fe(III)-citrate group also showed the fastest methane production rate, the efficiency of electron recovery in methane production was only 58-78%, which was evidently lower than that in both crystalline hematite (86-89%) and magnetite (93-97%) groups. Methane production rate with non-conductive ferrihydrite was nearly same as that with conductive magnetite, both of which were significantly higher than that with semi-conductive hematite. X-ray Diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis showed that sludge collected from hematite and magnetite group still respectively presented a relatively intact characteristic spectra involved in hematite and magnetite. Differently, the characteristic spectra involved in ferrihydrite was not evident in sludge collected from ferrihydrite group, whereas the characteristic spectra involved in magnetite was detected. Microbial community analysis showed that, both Fe(III)-citrate and ferrihydrite specially enriched Fe(III)-reducing bacteria capable of degrading phenol into fatty acids (Trichococcus and Caloramator) via dissimilatory Fe(III) reduction. Fe(III)-citrate also stimulated the growth of Syntrophus capable of degrading phenol/benzoate into acetate and proceeding direct interspecies electron transfer (DIET). In magnetite and hematite group, the abundance of Enterococcus species evidently increased, and they might proceed DIET with Methanothrix species in syntrophic conversion of fatty acids into methane.


Identification of novel neuronal isoforms of the Rho-GEF Trio.
The large family of GEFs (guanine nucleotide-exchange factors) for Rho GTPases activate the GTPases by accelerating their GDP/GTP exchange. The multidomain protein Trio is the founding member of an intriguing subfamily of Rho-GEFs exhibiting two Rho-GEF and numerous additional domains. The members of the Trio family play an important role in neuronal physiology, and their structural organization is very well conserved through evolution. It has previously been shown that all the members, except mammalian Trio, display several isoforms, the functions of which have been well established. In this study, we have identified, by a combination of different approaches, novel Trio isoforms that have been generated by alternative splicing, giving rise to proteins that exhibit one or two Rho-GEF domains (GEFDs). These isoforms are specifically expressed in the nervous system, at a higher level than the full-length Trio, which is ubiquitously expressed. In addition, we show that all the GEFD1-containing isoforms induce neurite outgrowth in neuroblastoma cells. We have identified neuronal specific isoforms of Trio which could be essential for Trio function in neuronal morphology.


Tyrosine 151 is part of the substrate activation binding site of bovine trypsin. Identification by covalent labeling with p-diazoniumbenzamidine and kinetic characterization of Tyr-151-(p-benzamidino)-azo-beta-trypsin.
Identification of the substrate activation site of beta-trypsin by a 1:1 reaction with p-diazoniumbenzamidine chloride was confirmed by spectral analysis. Proteolysis of Cm-p-benzamidino-azo-beta-trypsin provided peptides containing modified tyrosine residues. The major product, Ser-146 to Lys-156, which corresponded to labeling at Tyr-151, was recovered in 35% yield, and its structure was demonstrated by amino acid analysis, Edman degradation, and mass spectrometry. Yields of labeled Tyr-151, Tyr-39, and Tyr-172, identified by peptide analysis, were in the proportion of 100:7:3. Tyr-151-(p-benzamidino)-azo-beta-trypsin is permanently activated, but can be further activated by substrates. Values of kcat, Ks', and kcat' vary from two to three times the equivalent values for trypsin. Berenil (4,4'-diazoamino-bis-benzamidine), a parabolic competitive inhibitor of beta-trypsin, was a hyperbolic competitive inhibitor of azo-beta-trypsin. Thus, Tyr-151, part of subsite S'2, affects the catalytic process and, when modified covalently, permanently activates trypsin. Equilibrium binding with berenil supported the kinetic data obtained with substrates. This permits the integration of protein modification, kinetics, equilibrium binding, and crystallographic data to demonstrate a fine interaction between subsites S1-S3 and S'2 in trypsin and azo-beta-trypsin, resulting in subtle structural changes when the native enzyme is covalently modified at Tyr-151.


Comparison of fetal toxicity of various multi-wall carbon nanotubes in mice.
The fetal toxicities of multi-wall carbon nanotubes (MWCNTs) with various sizes were compared in CD1(ICR) mice. MWCNTs were suspended in 2% sodium carboxymethyl cellulose solution in phosphate-buffered saline. On day 9 of gestation, dams were administered a single intraperitoneal dose of MWCNTs (4 mg/kg body weight), while dams in the control group were administered vehicle (10 mL/kg body weight). The rectal temperatures of the dams were monitored 2 h after administaration to asses statuses of the dams. The dams and fetuses were examined on day 18 of gestation. The number of live fetus per dam decreased in some MWCNTs-administered groups. The mean percentages of live fetuses in total implantations in the MWCNTs-administered groups markedly varied from 0% to 95%, and the highest mean percentage of live fetuses in the MWCNTs-administered group was equivalent to that of the control group. The decrease in live fetuses depended on an increased number of early dead fetuses. In the groups with markedly lowered rectal temperature after administration, the fetal loss were evident. The blood levels of interleukin-6 and/or monocyte chemoattractant protein-1 in dam 2 h after administration of MWCNTs markedlyr increased, especially in the goups with significant decrease in live fetuses. These results indicated a relationship between inflammation in the dam, which probabely depended on the particular length of the MWCNTs, and the fetal toxicioty of MWCNTs in mice.


Tuning the plasmonic and catalytic signals of Au@Pt nanoparticles for dual-mode biosensing.
Dual-mode biosensors have gained great attention due to their excellent detection accuracy provided by the mutual verification of output signals. However, current strategies for dual-mode sensing mainly rely on a signal probe exhibiting dual properties that may encounter unreliability. Herein, we report a dual-mode biosensing strategy by modulating the plasmonic and catalytic activities of nanoparticles through a surface growing approach. Ascorbic acid enables the growing of Au shell on Au@Pt NPs to tune both their peroxidase-like activity and plasmonic signal. Enzyme-catalyzed reactions can generate ascorbic acid to modulate the plasmonic and catalytic activities of nanoparticles. Combined with enzyme-linked immunosorbent assay, it enables dual-mode immunoassays of carbofuran with both a colorimetric readout by a spectrometer down to 0.1 ppb and a naked-eye readout of 5 ppb. This dual-mode biosensing technique advantages in tunable sensitivity and robustness, holding promise as an analytical platform for biomedical diagnosis and food safety.


Case studies to illustrate good practice in the management of non-tuberculous mycobacterial pulmonary disease.
Pulmonary disease caused by non-tuberculous mycobacteria (NTM-PD) can be a complex condition for health care providers to manage, and delayed diagnosis and treatment failure are common. Here we present three case studies that illustrate key challenges in the diagnosis and treatment of NTM-PD, and provide guidance on these issues. In addition, we make recommendations on how the overall management of NTM-PD may be improved, through strategies such as physician education to recognise NTM-PD, and the development of multidisciplinary teams and patient-support groups.


Feasibility of a simple drainage system in Cameroonian children after thoracotomy and decortication for empyema thoracis.
To analyse the outcome of children with empyema thoracis treated by decortication followed by a simple drainage system. Retrospective chart review from July 2001 to June 2010 of all cases of children who had a thoracotomy for empyema. We used an endotracheal tube as chest drain and a urinary bag as a collector. Statistical analyses were done using EXCEL and SPSS 9.0. Forty one children underwent thoracotomy and decortication for empyema, there were 23 boys and 18 girls with a sex ratio of 1, 21. The mean age was 2½ years with a minimum of 1 month and a maximum of 15 years of age; 27 children were below two years of age. All the patients have received antibiotic for a long period before surgery. The culture was negative, except in two cases where we found Klebsiella pneumonia and Staphylococcus aureus. In five cases, the empyema was due to Mycobacterium tuberculosis. Three children presented a complication: One child had a persistent purulent drainage for 2 weeks; another one was re-operated upon because of necrotic lung abscess and one child died of sepsis. In most cases, the chest tube was removed between day 4 and day 6 post-operatively. The average length of hospital stay after the surgery was 10 days. Thoracotomy and decortication in children with empyema can be safely done in Cameroon using a simple drainage system with good results compared to those in the literature.


Understanding the patient and family experience of nutrition and dietetic support during childhood cancer treatment.
This study aimed to understand the experience of families caring for a child with cancer in New Zealand (NZ) who received nutrition and dietetic support during cancer treatment and their preferences for the delivery, format, and timing of nutrition information. Childhood cancer patients and their families (N = 21) participated in a mixed-methods study at a specialist paediatric oncology centre in Auckland, NZ. Before the semi-structured interview, participants completed a questionnaire capturing demographic, disease, and treatment characteristics of their child, their nutrition concerns, and their information needs. Quantitative data were described, and qualitative thematic analysis of the semi-structured interviews was performed using NVivo data analysis software. Eighty-six percent of participants indicated they had concerns about their child's nutrition during treatment. The most common concerns were anorexia, vomiting, and weight loss. While many were happy with the quality of the nutrition support received, one-third of the patients wanted more support. Four key themes emerged from the interviews: (1) patients experience significant and distressing nutrition challenges; (2) patients and families have mixed perceptions of EN; (3) there are gaps in the current nutrition support system for inpatients; and (4) a desire for more accessible nutrition support. Childhood cancer patients and families experience significant and distressing nutrition challenges during treatment. Standardising information given to patients and their families may optimise nutrition support for paediatric oncology patients and reduce the discordance between families and health professionals. Future implementation of a nutrition decision aid in this population is warranted.


B-type natriuretic peptide for assessment of haemodynamically significant patent ductus arteriosus in premature infants.
Haemodynamically significant patent ductus arteriosus (hsPDA) is frequently observed in premature infants. This study was conducted to explore whether the blood BNP can be a valuable biomarker to assess the necessity of treatment for hsPDA in premature infants. Serial measurements of the blood BNP were performed during the first 5 days of life in premature infants with hsPDA (Group I) and those without hsPDA (Group N). The definition of the hsPDA was the PDA requiring treatment, such as indomethacin administration and/or surgical ligation. Forty-six subjects were enrolled. Compared with Group N, Group I showed significantly higher level of blood BNP at postnatal 24-96 h and demonstrated the peak value at postnatal 24-48 h. With the ROC curve using the data at postnatal 24-48 h in Group I, we deduced the predictive value of 250 pg/mL of blood BNP for indomethacin treatment. Similarly, with the ROC curve using the maximal value of blood BNP within the first 5 days of life, the predictive value of 2000 pg/mL for surgical ligation was deduced. Blood BNP during early postnatal period can be a useful biomarker to assess the necessity of treatment for hsPDA in premature infants.


Characterization and Expression Analysis of Extradiol and Intradiol Dioxygenase of Phenol-Degrading Haloalkaliphilic Bacterial Isolates.
Haloalkophilic bacteria have a potential advantage as a bioremediation organism of high oil-polluted and industrial wastewater. In the current study, Haloalkaliphilic isolates were obtained from Hamralake, Wadi EL-Natrun, Egypt. The phenotype script, biochemical characters, and sequence analysis of bacterial-16S rRNA were used to identify the bacterial isolates; Halomonas HA1 and Marinobacter HA2. These strains required high concentrations of NaCl to ensure bacterial growth, especially Halomonas HA1 strain. Notably, both isolates can degrade phenol at optimal pH values, between 8 and 9, with the ability to grow in pH levels up to 11, like what was seen in the Halomonas HA1 strain. Moreover, both isolates represent two different mechanistic pathways for phenol degradation. Halomonas HA1 exploits the 1,2 phenol meta-cleavage pathway, while Marinobacter HA2 uses the 2,3 ortho-cleavage pathway as indicated by universal primers for 1,2 and 2,3 CTD genes. Interestingly, Marinobacter HA2 isolate eliminated the added phenol within an incubation period of 72 h, while the Halomonas HA1 isolate invested 96 h in degrading 84% of the same amount of phenol. Phylogenetic analysis of these 1,2 CTD (catechol dioxygenase) sequences clearly showed an evolutionary relationship between 1,2 dioxygenases of both Halomonadaceae and Pseudomonadaceae. In comparison, 2,3 CTD of Marinobacter HA2 shared the main domains of the closely related species. Furthermore, semi-quantitative RT-PCR analysis proved the constitutive expression pattern of both dioxygenase genes. These findings provide new isolates of Halomonas sp. and Marinobacter sp. that can degrade phenol at high salt and pH conditions via two independent mechanisms.


The effects of calcium channel blocking drugs on the thermotropic behavior of dimyristoylphosphatidylcholine.
The effects of four calcium channel blocking drugs, diltiazem, verapamil, nimodipine and nisoldipine, on the main phase transition of dimyristoylphosphatidylcholine have been studied by high resolution differential scanning calorimetry. In all cases, the phase transition temperature is lowered, though much more effectively by nimodipine and nisoldipine than by the other two drugs. Nimodipine and nisoldipine markedly reduce the enthalpy of transition while diltiazem and verapamil have no significant effect on the enthalpy within the drug concentration range studied. Analysis of the data in terms of ideal solution theory is presented. X-ray and neutron scattering studies indicate that nimodipine and verapamil differ significantly with respect to their location within a lipid bilayer, and this difference suggests a partial rationalization of the experimental results presented here.


Dual regulation of the LDL receptor--some clarity and new questions.
Upregulation of the expression of the LDL receptor (LDLR) gene does not always lead to an increase in the LDLR protein. While the mRNA expression of the LDLR and the newly studied proprotein convertase PCSK9 are coordinately upregulated in absence of sterols, the latter proteinase apparently enhances the degradation of the LDLR protein.


Associations of pre-pandemic levels of physical function and physical activity with COVID-19-like symptoms during the outbreak.
One's physical function and physical activity levels can predispose or protect from the development of respiratory infections. We aimed to explore the associations between pre-pandemic levels of physical function and physical activity and the development of COVID-19-like symptoms in Swedish older adults. We analyzed data from 904 individuals aged ≥ 68 years from the population-based Swedish National study on Aging and Care in Kungsholmen. COVID-19-like symptoms were assessed by phone interview (March-June 2020) and included fever, cough, sore throat and/or a cold, headache, pain in muscles, legs and joints, loss of taste and/or odor, breathing difficulties, chest pain, gastrointestinal symptoms, and eye inflammation. Muscle strength, mobility, and physical activity were examined in 2016-2018 by objective testing. Data were analyzed using logistic regression models in the total sample and stratifying by age. During the first outbreak of the pandemic, 325 (36%) individuals from our sample developed COVID-19-like symptoms. Those with slower performance in the chair stand test had an odds ratio (OR) of 1.5 (95% confidence interval [CI] 1.1-2.1) for presenting with COVID-19-like symptoms compared to better performers, after adjusting for potential confounders. The association was even higher among people aged ≥ 80 years (OR 2.6; 95% CI 1.5-4.7). No significant associations were found between walking speed or engagement in moderate-to-vigorous physical activity and the likelihood to develop COVID-19-like symptoms. Poor muscle strength, a possible indicator of frailty, may predispose older adults to higher odds of developing COVID-19-like symptoms, especially among the oldest-old.


Characterization of radiation sensitivity of human squamous carcinoma A431 cells.
Studies have been performed to investigate the radiosensitivity of human squamous carcinoma cells. A431 cells were grown in vitro as exponential and fed-plateau monolayer cultures or as multicellular spheroids. Radiobiological studies of various cultures showed that fed-plateau phase cells were more sensitive (D0 = 1.3 Gy) than exponentially growing cells (D0 = 1.5 Gy). After a single dose of 12 Gy or two doses of 6 Gy irradiation, A431 cultures exhibited a large capacity for potentially lethal damage (PLD) repair (PLD repair factor = 17), but a relatively small sublethal damage (SLD) repair. In order to measure the radiation sensitivity of proliferating (P) and quiescent (Q) cells, enriched populations of P- and Q-cells were isolated from A431 spheroids. Flow cytometric analysis with acridine orange (AO) staining demonstrated that there was a shift of the RNA histograms in fed-plateau and spheroid cultures towards lower values, suggesting the presence of a subpopulation of Q-cells. Centrifugal elutriation was used to isolate the Q-cells from dissociated spheroid cells. Coulter cell volume distributions and flow cytometric analysis showed that Q-cells had a small cell volume (approximately 1380 microns3), low RNA content and a G1-like DNA content. Continuous labelling experiments with tritiated thymidine confirmed the non-proliferating nature of the Q-cells. Irradiation of the Q-cells after isolation from spheroids with between 0 to 10 Gy showed that they were more radiosensitive (decreased D0) than the P-cells isolated from these spheroids. The latter were, however, similar in radiosensitivity to exponential G1 cells.


Minimal criteria for the diagnosis of prostate cancer on needle biopsy.
Increased clinical screening of men at risk for prostate cancer, and the realization of the benefits of performing multiple biopsies per prostate, have facilitated early detection of malignancy, while presenting the pathologist with a growing array of diagnostic findings. Interpretation of these findings requires discussion of the minimal criteria required for the diagnosis of cancer on needle biopsy within a wide spectrum of related histologic findings. This spectrum includes small acinar proliferations suspicious for but not diagnostic of cancer, benign mimics of cancer, the preinvasive entity of high-grade prostatic intraepithelial neoplasia, and various treatment effects. Clinical implications of these findings and other prognostic factors are detailed.


Effectiveness of a multi-component intervention to reduce delirium incidence in elderly care wards.
to examine the effect of a multi-component, delirium prevention intervention on rates of incident delirium for patients admitted to specialist elderly care wards. 'before' and 'after' study. three specialist elderly care wards in a general hospital. older people admitted as emergencies. a multi-component delirium prevention intervention that targeted delirium risk factors was implemented by clinical staff. Demographic information and assessments for delirium risk factors were recorded by research staff within 24 h of admission to the ward. New onset (incident) delirium was diagnosed by daily research staff assessments using the Confusion Assessment Method and Delirium Rating Scale-Revised-98. a total of 436 patients were recruited (249 in the 'before' and 187 in the 'after' group). Incident delirium was significantly reduced ('before' = 13.3%; 'after' = 4.6%; P = 0.006). Delirium severity and duration were significantly reduced in the 'after' group. Mortality, length of stay, activities of daily living score at discharge and new discharge to residential or nursing home rates were similar for both groups. a multi-component, delirium prevention intervention directed at delirium risk factors and implemented by local clinical staff can reduce incident delirium on specialist elderly care wards.


Renal cell carcinoma with heterotopic bone formation. Case report and review of the Japanese literature.
A case of renal cell carcinoma with heterotopic bone formation is presented. We will review the reports and radiographic findings of Japanese cases and comment on their hypovascularity.


Deployment-related PTSD symptomatology and social functioning: Probing the mediating roles of emotion regulation and mentalization in an outpatient veteran sample.
Deployment-related posttraumatic stress disorder (PTSD) impacts social functioning in families. Therefore, it is important to examine the factors that contribute to social functioning in families that are confronted with deployment-related PTSD. The goal of this study was to assess the association between PTSD symptom severity and social functioning using self-report questionnaires in an outpatient veteran sample and to test the mediating roles of emotion regulation (Study 1, N = 100) and mentalization (Study 2, N = 38). Study 1 demonstrated that emotion regulation problems fully mediated PTSD associated family dysfunctioning. Study 2 did not demonstrate a mediation role of mentalization, but also did not demonstrate an association between PTSD and social dysfunctioning. Maladaptive mentalization was associated with poor child adjustment. Critically, a between-study comparison revealed that PTSD symptom severity was significantly higher in Study 1 than in Study 2. Overall, our findings suggest that social dysfunctioning may only appear when a given severity threshold of PTSD is reached, in which emotion regulation might be a key clinical factor. Maladaptive mentalization may be critical for post-deployment child adjustment. Future research should further examine social functioning in samples with different PTSD severity profiles and include the role of mentalization. Longitudinal data are needed to gain further insight into the causal relationships among the factors considered and the etiological pathways that lead to developing social dysfunction over time.


Left ventricular rupture after mitral surgery: repair by patch and sealing.
Ventricular wall rupture after mitral valve replacement is an infrequent but dreaded complication. We have experienced this problem in two separate instances of type III left ventricular rupture and report the successful repair by a novel technique with the use of a new sealant, the AdvaSeal (FocalSeal), in a sandwitch repair procedure.


Fatal legionellosis in patients with malignant hematologic diseases.
Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period.


Glucagon-producing α-cell transcriptional identity and reprogramming towards insulin production.
β-Cell replacement by in situ reprogramming of non-β-cells is a promising diabetes therapy. Following the observation that near-total β-cell ablation in adult mice triggers the reprogramming of pancreatic α-, δ-, and γ-cells into insulin (INS)-producing cells, recent studies are delving deep into the mechanisms controlling adult α-cell identity. Systematic analyses of the α-cell transcriptome and epigenome have started to pinpoint features that could be crucial for maintaining α-cell identity. Using different transgenic and chemical approaches, significant advances have been made in reprogramming α-cells in vivo into INS-secreting cells in mice. The recent reprogramming of human α-cells in vitro is an important step forward that must now be complemented with a comprehensive molecular dissection of the mechanisms controlling α-cell identity.


Synthesis and characterization of thiosemicarbazone-functionalized organoruthenium (II)-arene complexes: Investigation of antitumor characteristics in colorectal cancer cell lines.
In the current study, organoruthenium(II)-arene complexes (I-IV) have been prepared by the reaction of [{(η6-p-cym)RuCl}2(μ-Cl)2] with new thiosemicarbazones (TSC1-4).The isolate was analyzed using elemental analysis, FT-IR, 1H and 13C NMR spectroscopy and single-crystal XRD. Subsequently, the complexes and TSC ligands were assessed for anticancer properties in vitro against three different colorectal cancer stage's cell lines (Caco-2, DLD-1, and SW620) and a noncancerous cell line (CCD18Co). The complexes (I-IV) showed higher cytotoxicity with low IC50 values as 0.1-0.33 μM in colorectal cell lines except for SW620 (47.4-84.20 μM) than in a noncancerous cell. Complex I was 2.8 and 24.5-fold more active against Caco-2 and DLD-1 than CCD18Co, respectively. The complexes (I-IV) accumulated at a high concentration in the cell nuclei and caused cell cycle arrest by affecting the G0/G1 and/or G2/M phase and showed high binding affinity with CT-DNA (Kb = 104 M-1). The expression of Caspase-3 and Caspase-9 apoptosis-related protein levels was slightly upregulated and Atg5 autophagy-related protein level was clearly downregulated according to control and 5-FU-treated cells after complex I and II treatment. Furthermore, it was observed that cytotoxicity of the complexes is decreased while cancer progresses. Altogether, this study indicates that all organoruthenium (II)-arene complexes (particularly complex I) can be a promising alternative to platinum counterparts in cancer treatment.


Hemispheric alpha asymmetries in fluent and dysfluent aphasics during linguistic and resting conditions.
The hemispheric alpha asymmetries of a group of normal males, normal females, fluent aphasic males and dysfluent aphasic males were investigated during the auditory presentation of sentences, a short story and a resting condition in the absence of linguistic stimuli. No differences were found for the groups' mean alpha ratio scores during the resting condition. Fluent aphasics were found to demonstrate greater right hemispheric alpha suppression than the other groups for the sentence and story conditions. The dysfluent aphasics showed greater right hemispheric alpha suppression for the sentence condition than either of the normal groups. Results are discussed in terms of the right hemisphere's contribution to language recovery following unilateral left hemispheric damage resulting in aphasia.


Dichoptic training enables the adult amblyopic brain to learn.
Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see.


The impact of temperature on the acute toxicity of arsenate and arsenite to rainbow trout (Salmo gairdneri).
This research investigated the influence of temperature (5 or 15 degrees C) on the acute toxicity of waterborne arsenite and arsenate to rainbow trout. Trout exposed to arsenate at 5 degrees C had a 144-hr LC50 (95% fiducial limits) of 114.1 (106.7 to 121.9) mg liter-1, twice the value of 58 (50.6 to 66.4) mg liter-1 evident in fish exposed at 15 degrees C. Temperature had no effect on the toxicity of arsenite; 144-hr LC50's at 5 and 15 degrees C were 17.7 (16.5 to 18.9) and 20.7 (19.9 to 21.5) mg liter-1, respectively. When fish were exposed to 70 mg liter-1 arsenate for 72 hr, those held at 15 degrees C had mean whole-body arsenic levels that were five times higher than the levels in fish held at 5 degrees C. There were, however, essentially no differences in the patterns of arsenic uptake between 5 and 15 degrees C when the fish were exposed to arsenate at 0.7 or 1.2 of the 144-hr LC50 at each temperature, a strategy which compensates for (eliminates) temperature as a modifier of toxicity. Fish which were held in arsenate-free water after the 72-hr arsenate exposure depurated significantly more arsenic at 15 degrees C than at 5 degrees C. Despite this, it is apparent that enhanced uptake at 15 degrees C was the overriding factor controlling the differences in the expression of arsenate toxicity at the two temperatures.


Health Shocks and Economic Well-being of the Aging Population: Evidence from Mexico.
We exploit the longitudinal Mexican Health and Aging Study to estimate the effects of health shocks in the short-run on the subsequent economic well-being of the aging population in Mexico. While there is substantial evidence indicating negative economic effects of such changes in industrialized countries, little is known about health impacts on the future economic position of older adults in low- and middle-income countries. This paper takes an important step towards filling this gap in knowledge. Our results are widely relevant, with a large percentage of the world's population residing in developing countries such as Mexico that are experiencing rapid aging. We find evidence of negative impacts of health shocks on subsequent economic well-being of older adults in Mexico, but the effect varies according to several dimensions. First, the impact is clearly on income, not wealth. Second, responses are heterogenous across sources of income, with evidence of an impact mainly on labor income. Third, we find clear differences by gender in the impact of a health shock, with a larger negative impact on men. Fourth, we conclude that the population groups most negatively affected are those with the greatest degree of vulnerability prior to the shock, as measured by education and access to health insurance. Even though Mexico has made important gains with anti-poverty programs such as the Programa 70+ pension and a move towards universal health insurance, additional interventions targeted at the most vulnerable subsets of the aging population might be warranted.


Network characteristic analysis of ADR-related proteins and identification of ADR-ADR associations.
Adverse drug reactions (ADRs) are caused by interactions between drugs or their metabolites and specific proteins. Knowledge of these proteins is important for facilitating mechanistic research of ADRs and new drug discovery. Here, we identified 41 network modules from an ADR-protein network; analysed the function of each module; revealed the potential accompanying actions of the ADRs and the new ADR-related proteins (ADRPs) to a unique ADR and studied the characteristics of composition, subcellular location and tissue distribution of these ADRPs by comparing them with drug-related proteins (DRPs). The results indicated that ADRs are mainly caused by risk drug-related proteins (RDRPs) and that drug off-target effects are a secondary cause. Biological processes that enzymes involve are the main reason for the occurrence of ADRs. However, drug-related transporters have a higher risk of inducing ADRs than drug-related enzymes do, and ADRPs locating in the cell membrane tend to induce multiple ADRs.


Is there evidence for efficacy of human papillomavirus vaccination in solid organ transplant recipients?
Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide and is associated with precancerous lesions and cancers of the cervix, vulva, vagina, penis, anus, tonsils and base of the tongue. Several studies show an increased risk of HPV-associated cancers in solid organ transplant recipients (SOTR). The aims of this review are to investigate the evidence of efficacy for the HPV vaccination in transplant recipients and to discuss the known national guidelines. A systematic literature search has been conducted to identify studies where SOTR received the HPV vaccination to evaluate the efficacy of the HPV vaccine on this population. The primary outcome was antibody response against the HPV genotypes included in the vaccines and the secondary outcome was national guidelines recommending HPV vaccination of SOTR. Three cohort studies evaluated immunogenicity. Two studies found suboptimal effect of the HPV vaccine, while an early terminated study detected 100% seropositivity. We have identified four national guidelines in the following countries; United States of America, Canada, Australia and Ireland, along with a recommendation from the World Health Organization (WHO). The results from the three studies were inconclusive due to the small sample sizes and the diverging results. Recommendations of HPV vaccination of SOTR is based on the knowledge about safety and efficiency in the general population and the safety of other inactivated (not live) vaccines in SOTR. Theoretically, the nonavalent vaccine should be recommended as the first choice in SOTR without age- or sex restrictions.


IL6-174 G/C gene polymorphism and its relation to serum IL6 in Egyptian children with community-acquired pneumonia.
Cytokines are involved in the pathogenesis of community acquired pneumonia (CAP). The aim of this study is to investigate the association of IL6-174 G/C gene polymorphism with CAP in Egyptian children, to assess its effect on CAP outcome and to determine its effect on the serum IL6 levels in these children. IL6-174 G/C gene polymorphism was genotyped in 210 Egyptian children (100 patients with CAP and 110 healthy controls) using PCR-RFLP, while the serum IL6 levels were measured by ELISA method. We found a significant association between the GG genotype, G allele of IL6-174 G/C SNP and susceptibility to CAP (P=0.02, 0.01 respectively). However, GG genotype and G allele were protective against severe sepsis (p=0.004), acute respiratory failure (p<0.001) and hospital mortality (p<0.001). Serum IL6 levels were significantly increased in these children while there was no relation between GG genotype and serum IL6. In conclusion, IL6-174 G/C gene polymorphism may contribute to susceptibility to CAP in Egyptian children.


Postnatal thyroid function in low birth weight infants: a cross-sectional assessment of free thyroxine and thyroid hormone binding globulin.
To investigate the significance of low serum thyroxine in premature infants, serum FT4, T4, TSH and TBG were measured in 7 infants with BW less than 1000 g, 8 infants with BW 1001 to 1350 g, 9 infants with BW 1351 to 2499 g, and 11 full-term infants. FT4 concentrations were lower in the LBW infants than in the FT infants. Percent FT4 values in the infants with BW less than 1000 g were the highest in the groups studied, so that FT4 concentrations in those infants did not fall proportionally with the marked T4 decrease. TBG concentrations were lower in the VLBW infants (less than BW 1350 g) than in the FT infants, and were positively correlated with BW and GA. This study suggests that in infants with lower birth weight there is a mechanism to prevent a decrease in FT4 concentrations associated with total T4 decrease. This fact may be a reason for euthroidism in small premature infants with low T4. Measurements of FT4 may be a useful adjunct to assessment of thyroid function in the VLBW infants with low T4.


The development and test of a device for the reconstruction of 3-D position and orientation by means of a kinematic sensor assembly with rate gyroscopes and accelerometers.
In this paper, we propose a device for the Position and Orientation (P&O) reconstruction of human segmental locomotion tasks. It is based on three mono-axial accelerometers and three angular velocity sensors, geometrically arranged to form two orthogonal terns. The device was bench tested using step-by-step motor-based equipment. The characteristics of the six channels under bench test conditions were: crosstalk absent, non linearity < +/- 0.1% fs, hysteresis < 0.1% fs, accuracy 0.3% fs, overall resolution better than 0.04 deg/s, 2 x g x 10(-4). The device was validated with the stereophotogrammetric body motion analyzer during the execution of three different locomotion tasks: stand-to-sit, sit-to-stand, gait-initiation. Results obtained comparing the trajectories of the two methods showed that the errors were lower than 3 x 10(-2) m and 2 deg during a 4s of acquisition and lower than 6 x 10(-3) m and 0.2 deg during the effective duration of a locomotory task; showing that the wearable device hereby presented permits the 3-D reconstruction of the movement of the body segment to which it is affixed for time-limited clinical applications.


Integrating the systematic assessment of psychological states in the epilepsy monitoring unit: Concept and compliance.
Admission to the epilepsy monitoring unit (EMU) for long-term video-electroencephalography (EEG) monitoring (VEEG) constitutes the gold standard for seizure diagnosis and presurgical evaluation. This study applied the concept of a high-frequency systematic monitoring of psychological states and tested patients' compliance in order to evaluate if its integration in the EMU is feasible and if patients benefit from the graphically underpinned discussion of their EMU stay-related cognitions and emotions. The process-monitoring is technically realized by an internet-based device for data collection and data analysis, the Synergetic Navigation System (SNS). A convenient sample was enrolled: All eligible patients who were admitted to the EMU of the Department of Neurology, Christian Doppler Medical Center, Salzburg, Austria, between November 6th 2017 and January 26th 2018 were approached and recruited upon consent. After a short resource-oriented interview, each enrolled patient was provided with a tablet. The daily questionnaire included eight standardized and up to three personalized items. Self-assessments were collected every 5 h prior to meal times (6:30 am, 11:30 am, and 4:30 pm) and at 9:30 pm. The detailed visualizations of the patients' replies were discussed with the participants during a feedback session at the end of the EMU stay. Twenty-one patients (12 women/9 men, median age 29 years [range 18-74 years]) were consecutively recruited (72% of all eligible patients). Compliance rates were high (median: 82%, range 60%-100%) among the respondents. Mood correlated strongly with hopefulness (r = 0.71) and moderately with energy (r = 0.63) in all patients. When correlating the intraindividual medians of the process questionnaire time series with the pretest total scores, energy correlated moderately and negatively with the Perceived Stress Scale (PSS) (r = -0.45), while self-efficacy correlated moderately and negatively with the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) total scores in all patients (r = -0.5). Nine patients (43%) reported that they learned something meaningful about themselves after the feedback discussion of their individual time series. The results support the feasibility of high-frequency monitoring of psychological states and processes in routine EMU settings. Repeated daily collections four times per day of psychological surveys allow for the assessment of highly resolved, equidistant time series data, which gives insight into psychological states and processes during EMU admission.


The 3' CCACCA sequence of tRNAAla(UGC) is the motif that is important in inducing Th1-like immune response, and this motif can be recognized by Toll-like receptor 3.
In this article, the immunogenicity of tRNA and the recognition of tRNA by Toll-like receptors (TLRs) are analyzed. Analyses of the effects of different tRNA(Ala)(UGC) fragments (tRNA(Ala)1-76 [corresponding to positions 1 through 76], tRNA(Ala)26-76, tRNA(Ala)40-76, tRNA(Ala)62-76, tRNA(Ala)1-70, tRNA(Ala)26-70, tRNA(Ala)40-70, and tRNA(Ala)62-70) on the immune responses of hepatitis B surface antigen (HBsAg) were performed with BALB/c mice. Results show that tRNA(Ala)1-76, tRNA(Ala)26-76, tRNA(Ala)40-76, and tRNA(Ala)62-76 adjuvants not only induced stronger T helper (Th) 1 immune responses but also cytotoxic-T-lymphocyte (CTL) responses relative to tRNA(Ala)1-70, tRNA(Ala)26-70, tRNA(Ala)40-70, and tRNA(Ala)62-70 adjuvants in HBsAg immunization. A deletion of the D loop (tRNA(Ala)26-76), anticodon loop (tRNA(Ala)40-76), or TpsiC (tRNA(Ala)62-76) loop of tRNA(Ala)(UGC) does not significantly decrease the adjuvant characteristic of tRNA(Ala)(UGC). However a deletion of the 3'-end CCACCA sequence (tRNA(Ala)1-70, tRNA(Ala)26-70, tRNA(Ala)40-70, and tRNA(Ala)62-70) of tRNA(Ala)(UGC) significantly decreased the adjuvant characteristic in Th1 and CTL immune responses. Moreover, the recognitions of different tRNA(Ala)(UGC) fragments by TLR3, TLR7, TLR8, and TLR9 were analyzed. Results show that a deletion of the 3' CCACCA sequence of tRNA(Ala)(UGC) significantly decreased the recognition by TLR3. We concluded that the 3' CCACCA sequence of tRNA(Ala)(UGC) is the important motif to induce Th1 and CTL responses and this motif can be effectively recognized by TLR3.


Outpatient pelvic lymph node dissection.
Staging pelvic lymph node dissection is an important part of the evaluation of most patients with prostatic carcinoma. While laparoscopic pelvic lymph node dissection provides an alternative to standard pelvic lymph node dissection, it has been associated with a significant learning curve, high major complication rate, frequent hospitalization and greater expense. We sought to modify the technique of pelvic lymph node dissection to allow its performance as an outpatient procedure. Pelvic lymph node dissection was performed through bilateral 3 cm. incisions overlying the obturator fossa in 11 patients. Nodes sampled ranged from 5 to 26 per patient that differed insignificantly from those undergoing standard pelvic lymph node dissection. Four patients had lymph node metastases. Nine procedures were performed entirely on an outpatient basis. One complication (external vein injury) was repaired with a single suture after extending the incision to 6 cm. Outpatient pelvic lymph node dissection through small incisions provides an attractive alternative to standard or laparoscopic lymph node dissection. With further experience it may become the procedure of choice for staging prostatic carcinoma in patients with a high risk of pelvic lymph node metastases.


Androgen-induced yawning in rhesus monkey females is reversed with a nonsteroidal anti-androgen.
In the adult rhesus monkey, yawning is an androgen-dependent sexually dimorphic behavior with males yawning more frequently than do females reflecting sex differences in circulating androgens. Studies in a variety of species indicate that yawning is mediated by various neurochemicals including dopamine, serotonin, and oxytocin. In rhesus monkeys, exogenous androgen reliably induces yawning in females to male-like levels. This study investigated whether flutamide, a nonsteroidal anti-androgen, reverses yawning induced by exogenous androgen administration in adult female rhesus monkeys. Six adult female rhesus monkeys were given chronic DHT alone and in combination with daily injections of flutamide and observed for yawning behavior. Treatment with DHT alone significantly increased yawning from 0.3 yawns per 30 min at the pretreatment baseline to 4.7 yawns per 30 min. Concurrent administration of flutamide significantly reduced the rate of yawning to 1.9 yawns per 30 min. These data indicate that flutamide is an effective tool for blocking the central effects of androgens in rhesus monkey females and that androgens regulate yawning similarly in both males and females.


First description of gastrointestinal nematodes of Barbary sheep (Ammotragus lervia): the case of Camelostrongylus mentulatus as a paradigm of phylogenic and specific relationship between the parasite and its ancient host.
The gastrointestinal helminth fauna of 24 Barbary sheep or Aoudad (Ammotragus lervia sahariensis) maintained in the Parque de Rescate de la Fauna Sahariana (PRFS, CSIC, Almeria, Spain) was analyzed. Most animals (87.5 %) were parasitized, and multiple infections were highly present. The following species were identified: Camelostrongylus mentulatus, Teladorsagia circumcincta, Marshallagia marshalli, Ostertagia ostertagi, O. leptospicularis, O. lyrata, Haemonchus contortus, Teladorsagia trifurcata, Trichostrongylus vitrinus, T. colubriformis, T. probolorus, T. capricola, Nematodirus spathiger, N. abnormalis, N. filicollis, N. helvetianus, Trichuris spp. and Skrjabinema ovis. Teladorsagia circumcincta was the most prevalent nematode in abomasum (52.6 %) followed by C. mentulatus (50 %). However, this latter nematode had the greater mean intensity and abundance. In the small intestine, T. colubriformis and T. vitrinus had the highest prevalence (36.4 %); the last one showed also the greater mean intensity and abundance. It should be emphasized the presence of Skrjabinema ovis (prevalence 39.1 %) in the large intestine, showing the greater mean abundance and intensity, although with a low values. Camelostrongylus mentulatus could be the most primitive nematode of the family trichostrongylidae recovered in this study; attending to its high prevalence, mean abundance and mean intensity, the possible specificity between this parasite and the Aoudad is discussed.


Artificial Intelligence in Drug Safety and Metabolism.
The use of artificial intelligence methods in drug safety began in the early 2000s with applications such as predicting bacterial mutagenicity and hERG inhibition. The field has been endlessly expanding ever since and the models have become more complex. These approaches are now integrated into molecule risk assessment processes along with in vitro and in vivo methods. Today, artificial intelligence can be used in every phase of drug discovery and development, from profiling chemical libraries in early discovery, to predicting off-target effects in the mid-discovery phase, to assessing potential mutagenic impurities in development and degradants as part of life cycle management. This chapter provides an overview of artificial intelligence in drug safety and describes its application throughout the entire discovery and development process.


[The assessment of glucose tolerance in hypertensive subjects treated with amlodipine].
The authors studied the side effects of amlodipine on glucose metabolism, carrying out an oral glucose tolerance test before and after 8-10 days of treatment, in a group of subjects with normal glucose tolerance. No significant variation in the average plasma glucose and insulin levels was observed. Nevertheless, in some cases, during amlodipine therapy, a decrease in glucose plasma level was found.


Clinical, Microbiological, and Molecular Characterization of Candia (Starmera) stellimalicola, a Rare Fungal Pathogen Causing Human Infections.
Candia (Starmera) stellimalicola is a yeast species spread worldwide and recovered from varieties of ecological reservoirs, but human infections are rarely reported. In this study, we reported an intra-abdominal infection case caused by C. stellimalicola and described its microbiological and molecular characteristics. C. stellimalicola strains were isolated from ascites fluid of an 82-year-old male patient having diffuse peritonitis with fever and elevated WBC counts. Routine biochemical and MALDI-TOF MS methods failed to identify the pathogenic strains. Phylogenetic analysis of 18S, 26S and internal transcribed space (ITS) rDNA regions, as well as whole-genome sequence identified the strains as C. stellimalicola. Compared with other Starmera species, C. stellimalicola had unique physiological characteristics including thermal tolerance (able to grow at 42 °C), which may prompt its environmental adaptability and potential for opportunistic human infection. Fluconazole minimum inhibitory concentration (MIC) values of the strains identified in this case was 2 mg/L, and the patient had a favorable outcome after receiving fluconazole treatment. In comparison, the majority of C. stellimalicola strains previously documented had high MIC values (≥ 16 mg/L) to fluconazole. In conclusion, with the raise in human infections caused by rare fungal pathogens, molecular diagnostic remains the most efficient way for accurate species identification; and antifungal susceptibility testing is essential to guide proper patient management.


Awareness, expectation and satisfaction towards ward pharmacy services among patients in medical wards: a multi-centre study in Perak, Malaysia.
Patient's awareness and satisfaction towards ward pharmacy services may influence perception towards effectiveness and safety of drugs, affecting medication adherence and clinical outcome. Nevertheless, studies on local ward pharmacy services were lacking. This study evaluated awareness, expectation and satisfaction of ward pharmacy services among patients in medical wards and determined their association with demographic characteristics. This was a cross-sectional study using self-administered questionnaire conducted in medical wards of fourteen Perak state public hospitals from September to October 2020. In-patients aged ≥18 years old were included. The validated questionnaire had four domains. The student's t-test, one-way analysis of variance (ANOVA) and multiple linear regression were was employed to evaluate the association between patients' demographic characteristics with their awareness, expectation and satisfaction towards ward pharmacy services. 467 patients agreed to participate (response rate = 83.8%) but only 441 were analysed. The mean age of the patients was 54.9 years. Majority was male (56.2%), Malay (77.3%), with secondary education (62.9%), rural resident (57.1%) and reported good medication adherence (61.6%). The mean awareness score was 49.6 out of 60. Patients were least aware about drug-drug interaction (3.85 ± 1.15) and proper storage of medications (3.98 ± 1.06). Elderly patients (β = - 2.82, P < 0.001) obtained lower awareness score. Patients with tertiary education (β = 3.87, P = 0.001), rural residents (β = 3.65, P < 0.001) and with good medication adherence (β = 2.55, P = 0.002) had higher awareness score. The mean expectation score was 44.0 out of 50. The patients had higher expectation to encounter a polite ward pharmacist (4.51 ± 0.56). Patients with tertiary education (β = 1.86, P = 0.024), rural residents (β = 1.79, P = 0.001) and with good medication adherence (β = 1.48, P = 0.006) demonstrated higher expectation. The mean satisfaction score was 43.6 out of 50. The patients had high satisfaction in language used (4.45 ± 0.57) and level of knowledge demonstrated (4.41 ± 0.62) by the ward pharmacists. Patients with tertiary education (β = 2.16, P = 0.009), rural residents (β = 1.82, P = 0.001) and with good medication adherence (β = 1.44, P = 0.009) demonstrated higher satisfaction, while elderly patients (β = - 1.17, P = 0.031) had lower satisfaction towards ward pharmacy services. There was a high level of awareness, expectation and satisfaction towards ward pharmacy services in public hospitals of Perak, Malaysia.


The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model.
Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF. Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery-external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations. Postoperative DVP increased significantly in venous hypertension group compared to control group (35 +/- 5 vs 13 +/- 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 +/- 8 vs 86 +/- 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 +/- 8 vs 64 +/- 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 +/- 16 vs 72 +/- 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells (r = -0.702, P = .0089). These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF.


The effect of transposition to jejunum on epithelial cell kinetics in an ileal segment.
Epithelial cell kinetics were studied in an ileal segment after transposition to proximal jejunum. The number of cells per villus column in the transposed ileum increased after 4--7 days to reach values normal for jejunum after 14--30 days. This increase was accompanied by a simultaneous increase in the number of cells per crypt column up to 130% of values in jejunum and ileum in situ. The percentage of labelled crypt cells, after labelling with 3H-thymidine, and the relative size of the proliferative cell compartment in the crypt in the transposed ileum did not differ from values in the ileum in situ at any time interval after surgery. The total proliferative activity per crypt, which was determined by scintillation counting of isolated crypts after 3H-thymidine labelling, increased two-fold from 7 days after surgery. Cell migration studies showed that the increase in the number of villus cells was probably not caused by a change in the life span of the epithelial cells. It seems that the increase in the number of villus cells in ileal epithelium after transposition to proximal jejunum is brought about by an enlargement of the crypt, while the relative size of the proliferative cell compartment in the crypt remains unchanged.


The current state of genetic counseling before and after amniocentesis for fetal karyotyping in Japan: a survey of obstetric hospital clients of a prenatal testing laboratory.
Pregnant women undergoing prenatal genetic testing should receive genetic counseling so they can make informed decisions. We examined the current state of providing genetic counseling in Japan to pregnant women before they elected amniocentesis for prenatal diagnosis of chromosome abnormalities and after test results were completed, and explored the opportunity for expanding access to certified genetic counselors (CGC) at clinical practices offering amniocentesis. An anonymous survey was mailed to the 298 hospitals that referred amniotic fluid specimens to LabCorp Japan in 2009. Most genetic counseling was provided by the obstetrician alone; 73.8 % (76/103) of pre-amniocentesis, 82.5 % (85/103) if normal results, and 49.4 % (44/89) if abnormal results. Respondents spent limited time in genetic counseling; 57.3 % spent <10 min for pre-amniocentesis, 88.3 % spent <10 min for normal results, and 54.0 % spent <20 min for abnormal results. While 45.8 % indicated that CGC do not have an essential role in clinical practice, responses that supported employment of CGC were more likely to come from hospitals that submitted more than ten specimens annually (p < 0.0001), university hospitals (p < 0.0001), and MD geneticists (p = 0.020). Currently, there is limited genetic counseling available in Japan. This indicates there are opportunities for the employment of CGC to improve the quality of genetic counseling.


Hepatitis E virus in blood donors from Argentina: A possible source of viral infection?
The hepatitis E virus (HEV) causes acute hepatitis, which can progress to chronicity in immunosuppressed patients. It is transmitted mainly by the fecal-oral or zoonotic routes, but there is current evidence that it can be transmitted by blood transfusions. The objective of the study was to investigate HEV infections in blood donors in Argentina, within the framework of a hemovigilance program. A total of 547 samples from Argentinean blood donors, collected in 2016, 2019 and 2020 was studied for IgG and IgM anti-HEV by ELISA (Diapro) and RNA HEV by RT-real time PCR and RT-Nested-PCR. The prevalence of IgG anti-HEV was 3.47% (19/547). No significant differences were registered according to the year studied, sex or age. The presence of RNA HEV was observed in 0.18% (1/547) of the donors studied without serological evidence of infection. This is the first molecular detection in blood donors from Argentina, showing a molecular prevalence within the range described for RNA-HEV in blood donors from other non-endemic countries, in which immunocompetent RNA-HEV positive donors without serological evidence of infection were identified. The presence of viraemic donors could imply transfusion transmission, which deserves further attention and study.


Switching between filter settings reduces the efficient utilization of visual working memory.
The capacity limitation of working memory requires that only relevant information gains access to the workspace, while irrelevant information is kept out. Thus, the ability to use attention to filter out irrelevant information is an important factor in how efficiently the limited storage space is used. Here, we examined to what degree the requirement to flexibly change filter settings affects filtering efficiency. Participants were presented with visual objects in different colors, and a cue presented in advance indicated which objects had to be stored. The contralateral delay activity, an event-related brain potential that reflects working-memory load was used to assess filtering efficiency during the retention interval. The data of two experiments showed that when filter settings had to be adjusted on a trial-by-trial basis, more irrelevant information passed the gate to working memory. Moreover, this switching-induced filtering deficit was restricted to those items that matched the previous, but currently irrelevant, filter settings. Thus, lingering effects of the selection history seem to counteract goal-directed encoding, and thus constitute an important attentional limitation for the efficient utilization of our limited workspace.


Solitary Neurofibroma of the Soft Palate: A Rare Entity.
The solitary neurofibroma is a benign tumor of neuronal origin uncommonly reported in the oral cavity. The possible association of this neoplasia with systemic pathologies, such as von Recklinghausen's disease and multiple endocrine neoplasia, makes its diagnosis fundamental. Solitary isolated neurofibroma of the soft palate not associated with von Recklinghausen's disease is an unusual tumor and probably only four cases have been reported in English literature previously. To the best of our knowledge, our case of soft palate neurofibroma in 17-year-old male represents the fifth reported in English literature, for which complete surgical excision was achieved with uneventful healing.


Effect of duration and age at exposure to the Stroke Belt on incident stroke in adulthood.
To assess whether there are differences in the strength of association with incident stroke for specific periods of life in the Stroke Belt (SB). The risk of stroke was studied in 24,544 black and white stroke-free participants, aged 45+, in the Reasons for Geographic and Racial Differences in Stroke study, a national population-based cohort enrolled 2003-2007. Incident stroke was defined as first occurrence of stroke over an average 5.8 years of follow-up. Residential histories (city/state) were obtained by questionnaire. SB exposure was quantified by combinations of SB birthplace and current residence and proportion of years in SB during discrete age categories (0-12, 13-18, 19-30, 31-45, last 20 years) and entire life. Proportional hazards models were used to establish association of incident stroke with indices of exposure to SB, adjusted for demographic, socioeconomic (SES), and stroke risk factors. In the demographic and SES models, risk of stroke was significantly associated with proportion of life in the SB and with all other exposure periods except birth, ages 31-45, and current residence. The strongest association was for the proportion of the entire life in SB. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in SB in adolescence (hazard ratio 1.17, 95% confidence interval 1.00-1.37). Childhood emerged as the most important period of vulnerability to SB residence as a predictor of future stroke. Improvement in childhood health circumstances should be considered as part of long-term health improvement strategies in the SB.


[Gastric cancer treated by hematoporphyrin derivative(HPD)-laser--histopathological study of 10 gastrectomy specimens].
10 patients with gastric carcinoma treated by HPD-laser preoperatively are reported. The gastric lesions were irradiated with laser beam delivered by a quartz fibre through the fiberoptic gastroscope 48-72 hours after intravenous injection of HPD (5.0 mg/kg) about 2 weeks before operation. In the resected specimens, the histological changes following HPD-laser therapy were studied. The cancer cells in the irradiated areas showed degeneration and necrosis in varying degrees. Because of the fact that the light spots were small and the penetration not deep enough, the cancer cells beyond the irradiated area and those infiltrating more deeply or beyond the gastric wall did not show any evident changes while metastatic cancers in the lymph nodes showed no changes at all. These facts may suggest that the HPD-laser therapy should not be used as the main therapeutic method to replace operation, radiotherapy or chemotherapy for gastric cancers in either advanced or early stage.


Developing clinical quality indicators for a Bi-National Burn Registry.
Clinical quality indicators are routinely used to benchmark and drive improvements in healthcare. There is a dearth of standardised clinical quality indicators established for management of burns that allow quality of care to be monitored and benchmarked across Australia and New Zealand. Using published quality indicator development processes and clinician experience, the Bi-National Burn Registry (Bi-NBR) working party developed quality indicators for burn care to be included as routine data items in the Bi-NBR. Twenty indicators covering structure, process and outcome measures were identified. Preliminary testing resulted in further revision to the quality indicators to increase validity, reliability and improve data quality. The quality indicators are routinely collected in the Bi-NBR and reported quarterly. This is the first published account of the development and testing of standardised Bi-National clinical quality indicators for burns. The Bi-NBR quality indicators project remains a work in progress and it is hoped that further refinement of the indicators, in conjunction with international collaborators will assist in driving improvements in burn care.


Neurological complications and myelographic features of achondroplasia.
The neurological complications of achondroplasia are discussed based on the literature and two of our cases. Thoracolumbar kyphosis, hypertrophic osteoarthritis, and intervertebral disc herniations may cause early neurological disturbances to adult achondroplasts owing to the spinal stenosis. The symptoms range from nerve root compression syndromes to complete transverse myelopathy. The radiographic features are characteristic, but the value of myelography for etiological clarification and location of the pathological process is limited. The significance of early symptoms and signs must be stressed and early decompression performed, as results are very disappointing once extensive neurological damage has occurred. An extensive laminectomy is usually indicated.


Targeted RNA interference of PI3K pathway components sensitizes colon cancer cells to TNF-related apoptosis-inducing ligand (TRAIL).
The phosphoinositide 3-kinase (PI3K/Akt) pathway transduces signals initiated from growth factors. Previously, we identified an important role for PI3K/Akt in colon cancer progression. The purpose of this study was to determine (1) whether short interfering RNA (siRNA) directed to PI3K/Akt components can render colon cancer cells sensitive to treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and (2) the cellular mechanisms contributing to the enhanced sensitivity. Human colon cancer cells KM20 and KM12C (both TRAIL resistant) were transfected with siRNA directed against the PI3K p85alpha regulatory subunit Akt1 or nontargeting control sequence and then treated with TRAIL (100 ng/mL) or vehicle. A ribonuclease protection assay was performed to assess changes in TRAIL receptor expression. Protein was extracted and analyzed by Western blot for expression of cleavage of TRAIL receptors (death receptor (DR) 4 and 5), caspase-3, caspase-8, and BID. Apoptosis was measured by enzyme-linked immunosorbent assay of DNA fragmentation. Combination treatment with p85alpha or Akt1 siRNA and TRAIL increased apoptosis in KM20 and KM12C cells, compared with TRAIL alone; these results were corroborated further by complete inhibition of apoptosis by Z-acetyl-Asp-Glu-Val-Asp-(DEVD)-fmk, a caspase-3 inhibitor. Furthermore, siRNA-mediated PI3K pathway inhibition resulted in increased expression of the TRAIL death receptors 4 and 5. Inhibition of PI3K/Akt by RNA interference sensitizes resistant colon cancer cells to TRAIL-induced cell death through the induction of TRAIL receptors and activation of caspase-3 and caspase-8. Agents that selectively target the PI3K/Akt pathway may enhance the effects of chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.


Long-term data from field erosion plot studies in eastern Austria.
Soil erosion and runoff data are collected at three sites in eastern Austria using field erosion plots. Observed treatments include 1) conventional tillage with plough (CT), 2) mulch tillage with winter cover crop (MT), and 3) no-till with winter cover crop (NT). Data cover a time span from 1994 to 2018. They include data about surface runoff, soil loss, nitrogen, phosphorus and soil organic carbon losses as well as cop yields associated with the erosion processes. Interpretation of the data will be found in "Long-term experience with conservation tillage practices in Austria: impacts on soil erosion processes" [1].


Sodium-dependent D-glucose transport in brush-border membrane vesicles after massive distal small bowel resection in the rat.
Massive small intestinal resection in the rat results in both structural and functional changes in the residual small bowel. Sodium-dependent D-glucose transport was examined in brush-border membrane vesicles derived from the proximal small bowel mucosa of male Sprague-Dawley rats 2 and 6 wk after a 66% distal jejunoileal resection or jejunoileal transection. Kinetic characteristics for the low-affinity, high-capacity system and high-affinity, low-capacity system were defined with rapid filtration under conditions of a zero-trans, 100 mM cis-NaSCN gradient. Mucosal weight, protein, and deoxyribonucleic acid content were increased in the residual intestinal segment compared to transected controls and morphometric studies revealed increased villus and crypt heights as well as an increased mitotic index. Postresection mean kinetic parameters for D-glucose transport at 2 wk (low-affinity system: Km, 177.5 +/- 45.1 microM; Vmax, 3.73 +/- 0.99 nmol X mg protein-1 X min-1; and high-affinity system: Km, 6.2 +/- 1.9 microM; Vmax, 0.12 +/- 0.06 nmol X mg protein-1 X min-1) and 6 wk (low-affinity system: Km, 267.8 +/- 83.1 microM; Vmax, 0.06 +/- 0.01 nmol X mg protein-1 X min-1; and high-affinity system: Km, 6.5 +/- 1.1 microM; Vmax, 0.06 +/- 0.01 nmol X mg protein-1 X min-1) were similar to values post-transection at 2 wk (low-affinity system: Km, 280.4 +/- 53.7 microM; Vmax, 3.05 +/- 0.32 nmol X mg protein-1 X min-1; and high-affinity system: Km, 9.1 +/- 1.3 microM; Vmax, 0.17 +/- 0.01 nmol X mg protein-1 X min-1) and 6 wk (low-affinity system: Km, 271.7 +/- 17.5 microM; Vmax, 4.69 +/- 0.23 nmol X protein-1 X min-1; and high-affinity system: Km, 10.6 +/- 4.2 microM; Vmax, 0.16 +/- 0.09 nmol X mg protein-1 X min-1). These kinetic data suggest that the hyperplastic response in adapting proximal small bowel after distal resection is accompanied by a persistence of the membrane functional characteristics for both sodium-dependent D-glucose transport systems despite an altered pattern of enterocyte proliferation and differentiation.


Role of the neocortex in consolidation of fear conditioning memories in rats.
The aim of the present work was to investigate, by means of the reversible inactivation technique, the distinct roles of three neocortical sites, the Prefrontal (PFC), Frontal (FC) and Parietal (PAC) cortices, during memory consolidation of conditioned freezing to a tone, a defined conditioned stimulus (CS), and to the training context. Reversible tetrodotoxin inactivations were performed at increasing post-acquisition delays (0.25, 24 or 96 h). Retention testing was always performed 72 h after the inactivation procedure in order to avoid any possible influence on the retrieval phase. It was found that none of the three sites are involved in context freezing consolidation, but that FC and PAC are differentially involved in the consolidation of memory to the CS. FC inactivation was followed by retention impairment only when performed immediately after acquisition while PAC inactivation was followed by amnesia when performed both immediately after acquisition and 24 h later, but not when performed 96 h later. PFC inactivation was not followed by retention impairment at any of the employed delays. These findings show that some neocortical structures are involved in auditory-cued fear conditioning during the initial phases of the consolidation process.


Congenital and infantile myotonic dystrophy.
Myotonic dystrophy (DM) encompasses two gene defects, DM1 (myotonic dystrophy type 1) being currently the sole disorder leading to a childhood form of the disease. As consequence of the non coding unstable CTG repeat expansion mutation, DM1 presents as an extremely wide and diverse clinical continuum ranging from antenatal to late adult forms, the complexity of the disease being reinforced by multisystemic involvement. The congenital form appears as the most severe end of the phenotypic spectrum and may include marked neonatal hypotonia, respiratory failure, facial diplegia, contractures, and mental retardation. Brain involvement is the hallmark of childhood-onset DM1, distinguished by a normal neonatal period, with learning difficulties as the main presenting symptom, resulting from various degrees of mental delay, psychopathological manifestations, speech defects, hypersomnolence, and fatigue. In contrast, muscle weakness remains usually moderate in childhood, limited to facial weakness, ptosis, and dysarthria, until a decline from the second decade. Orthopedic manifestations including kyphoscoliosis and equinovarus may require surgery. Other organs involvement includes frequent abdominal symptoms, whereas endocrine disturbance is rare. Symptomatic cardiac arrhythmia, mainly exercise-induced, can be observed. While current treatment is mainly symptomatic, future clinical trials are expected following significant progress in pathophysiology and the recent development of molecular therapy approaches.


Predicting miRNA-disease associations using improved random walk with restart and integrating multiple similarities.
Predicting beneficial and valuable miRNA-disease associations (MDAs) by doing biological laboratory experiments is costly and time-consuming. Proposing a forceful and meaningful computational method for predicting MDAs is essential and captivated many computer scientists in recent years. In this paper, we proposed a new computational method to predict miRNA-disease associations using improved random walk with restart and integrating multiple similarities (RWRMMDA). We used a WKNKN algorithm as a pre-processing step to solve the problem of sparsity and incompletion of data to reduce the negative impact of a large number of missing associations. Two heterogeneous networks in disease and miRNA spaces were built by integrating multiple similarity networks, respectively, and different walk probabilities could be designated to each linked neighbor node of the disease or miRNA node in line with its degree in respective networks. Finally, an improve extended random walk with restart algorithm based on miRNA similarity-based and disease similarity-based heterogeneous networks was used to calculate miRNA-disease association prediction probabilities. The experiments showed that our proposed method achieved a momentous performance with Global LOOCV AUC (Area Under Roc Curve) and AUPR (Area Under Precision-Recall Curve) values of 0.9882 and 0.9066, respectively. And the best AUC and AUPR values under fivefold cross-validation of 0.9855 and 0.8642 which are proven by statistical tests, respectively. In comparison with other previous related methods, it outperformed than NTSHMDA, PMFMDA, IMCMDA and MCLPMDA methods in both AUC and AUPR values. In case studies of Breast Neoplasms, Carcinoma Hepatocellular and Stomach Neoplasms diseases, it inferred 1, 12 and 7 new associations out of top 40 predicted associated miRNAs for each disease, respectively. All of these new inferred associations have been confirmed in different databases or literatures.


Accuracy of computational pressure-fluid dynamics applied to coronary angiography to derive fractional flow reserve: FLASH FFR.
Conventional fractional flow reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary injury, minimize technical limitations, and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR. The FLASH FFR study was a prospective, multicentre, single-arm study conducted at six centres in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30-90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with thrombolysis in myocardial infarction (TIMI) frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018, matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54 ± 1.48 min. caFFR was highly correlated to FFR (R = 0.89, P = 0.76) with a mean bias of -0.002 ± 0.049 (95% limits of agreement -0.098 to 0.093). The diagnostic performance of caFFR vs. FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0%, and area under the receiver operating characteristic curve of 0.979. Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity, and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity. URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.


Assessing the rates of error and adverse events in the ED.
The incidence of errors and adverse events in emergency medicine is poorly characterized. The objective was to systematically determine the rates and types of errors and adverse events in an academic, tertiary care emergency department (ED). Prospective data were collected on all patients presenting to a tertiary-care academic medical center ED with an annual census of 55,000 patients between January 2009 and November 2012. Cases of patients meeting predetermined criteria were systematically identified by an electronic medical record system. Criteria for review included patients who (1) returned to the ED within 72 hours and were admitted on their second visit, (2) were admitted from the ED to the floor and then transferred to the intensive care unit (ICU) within 24 hours, (3) expired within 24 hours of ED arrival, (4) required airway management, or (5) were referred to the QA committee as the result of complaints. Cases were randomly assigned to individual physicians not involved with the care. All cases were reviewed using a structured electronic tool that assessed the occurrence of error and adverse events. Institutional review board jurisdiction was waived by the Beth Israel Deaconess Medical Center IRB. During the study period, 152,214 cases were screened and 2131 cases (1.4%) met prespecified criteria for review. The incidence of error in these cases was 9.5% (95% confidence interval [CI], 8.3%-10.8%), representing an overall incidence of 0.13% among all ED patients. In cases that involved error, 50.5% occurred among patients who returned to the ED within 72 hours; 17.3% occurred among floor-to-ICU transfers; 5.4% occurred among mortality cases; 2.0% occurred among airway cases; and 24.8% occurred among cases referred as the result of complaints. The incidence of adverse events in the reviewed cohort was 8.3% (CI, 7.2%-9.6%), representing an overall incidence of 0.11% among all ED patients. In cases that involved adverse events, 48.6% occurred among patients who returned to the ED within 72 hours; 16.4% occurred among floor-to-ICU transfers; 9.0% occurred among mortality cases; 1.1% occurred among airway cases; and 24.9% occurred among cases referred as the result of complaints. Although the overall incidence of error and adverse events in EDs is low, the likelihood of such events is markedly increased among patients who return to the ED within 72 hours, among patients who require floor-to-ICU transfer within 24 hours, and among those whose cases come to attention as the result of complaints.


Spatial-temporal trends in global childhood overweight and obesity from 1975 to 2030: a weight mean center and projection analysis of 191 countries.
The geographic information science-based interactive map provided good prospects for the public health to study disease prevalence. The purpose of this study is to understand global spatial-temporal trends of childhood overweight and obesity and underlying causes help formulating intervention strategies. This multiple cross-sectional study included data on childhood overweight and obesity prevalence, gross national income per capita, and urbanization rate for 191 countries from 1975-2016. Autoregressive integrated moving average model, standard deviational ellipse model and mixed-effects models were used to explore spatial-temporal trends of childhood overweight and obesity and associations with gross national income per capita and urbanization rate. Globally, childhood overweight and obesity rate would reach 30.0% in 2030 (boys: 34.2%, girls: 27.4%). By 2030, it would reach 58.3% in middle- and high-income countries and 68.1% in Western Pacific region. Spatial-temporal trendline for childhood overweight and obesity in 1975-2030 exhibited a "C" shape, migrating from 1975 (15.6。E, 24.6。N) to 2005 (10.6。E, 21.7。N), then to 2030 (14.8。E, 17.4。N). The trendline for urbanization rate was also an irregular "C", and the turning point appeared five years earlier than childhood overweight and obesity. Globally, childhood overweight and obesity prevalence will continue to increase. Its weight mean center migrated from western countries to Asia and Africa following economic development.


Feasibility of using calibrated cone-beam computed tomography scans to validate the heart dose in left breast post-mastectomy radiotherapy.
In post-mastectomy radiotherapy, high-conformal techniques are a valid method for determining the dose distribution around a target. However, the proximity of critical structures is a reason for concern. This study aims to evaluate the feasibility of using calibrated cone-beam computed tomography (CBCT) scans as a valid tool for a timely heart dose evaluation. A retrospective analysis was conducted on 170 retrospective CBCT scans of 17 patients who underwent high-conformal post-mastectomy irradiation. The delivered doses that were calculated using personalized calibrated CBCT were compared with the doses planned, using the dose-volume histogram dosimetric parameters. The heart volume that was evaluated using CBCT presented a mean increase of 6%; this discrepancy impacted the heart dose in 4 of 17 patients, with an absolute increase of V25 Gy (range, 2.5%-7.6%) and an increase in the mean dose (range, 1.1-3.4 Gy). The dose for the target, ipsilateral lung, and contralateral breast remained unchanged. Using CBCT to monitor the dose that is delivered to the heart is feasible, allowing for a timely shift to an adaptive plan if clinically necessary.


Evaluation of the depth score of type V pit patterns in crypt orifices of colorectal neoplastic lesions.
We developed and evaluated the clinical usefulness of a scoring system that subclassified type VI: pit patterns. We studied 119 colon cancer lesions (pTis, n = 26; pT1, n = 93) and 22 tubular adenoma lesions with severe atypia in which a type VI: pit pattern was visible under a stereomicroscope. Four type VI: pit pattern formation appearances (existing pits, marginal irregularities of the gland duct, narrowing of the gland duct lumen, and unclear outline of the gland duct) were defined, and the relationship between each appearance and the invasive depth of the cancer was evaluated. When the four type VI: pit pattern appearances were considered in a logistic regression analysis, the odds of a more invasive submucosal cancer were significantly increased by the appearance of marginal irregularities, a narrowed lumen, and an unclear outline. In the logistic regression analysis results, when 0.63 was used as the cutoff score for prediction of a more invasive submucosal cancer, 80 cases in the less invasive group were classified correctly (specificity, 1.0), whereas 53 (86.9%) of the 61 cases in the more invasive group were classified correctly (sensitivity, 0.869). It is important first to understand the usability and limitations of objective scoring of type V pit pattern findings and then to apply this score to the determination of cancer depth in order to accurately identify lesions suitable for endoscopic treatment.


Survey of Aspergillus and Fusarium species and their mycotoxins in raw materials and poultry feeds from Córdoba, Argentina.
The aims of the present work were: (1) to determine both mycobiota in raw materials and finisher poultry feed, as well as the ability to produce aflatoxin B1 by A. flavus strains, and (2) to evaluate the natural co-occurrence of aflatoxins (AFs), fumonisins (FBs), gliotoxin, diacetoxyscirpenol (DAS), HT-2 toxin, and T-2 toxin in poultry feed by LC-MS/MS. Nineteen percent of raw materials and 79% of finisher poultry feed samples exceeded the maximum allowed total fungal count (1 × 10(4) CFU g(-1)) to ensure hygienic quality. Aspergillus flavus was the only species belonging to section Flavi which was isolated while Fusarium verticilliodes was the prevalent species. Forty-seven percent of A. flavus strains were aflatoxin B1 producers and the highest frequency of aflatoxigenic strains was isolated from finisher poultry feeds. Principal component analysis showed that corn grains are closely related with total fungal and Fusarium counts. This positive relationship suggests that total fungal and Fusarium spp. counts in poultry feed might come mainly from corn grains. Regarding poultry feeds, in ground finisher type, Aspergillus spp. counts increased as water activity (aw) diminished. A positive relationship among aw, total fungal and Fusarium spp. counts was observed in both ground finisher and ground starter feed. Several mycotoxins were monitored in feeds by applying the LC MS/MS technique. One hundred percent of poultry samples were contaminated with FB1, and the highest levels were detected in pelleted finisher poultry. AFB1, gliotoxin, DAS, HT-2 toxin, and T-2 toxin were not detected in any poultry feed. The scarcity of available mycotoxicological studies from Argentinean poultry feed using a multitoxin analysis technique enhances the contribution of the findings of this report.