[Management of uveal melanomas, guidelines for oncologists].
Uveal melanomas are the most frequent primary malignant eye tumor. Enucleation was historically the gold standard. Since then, several studies showed that conservative treatments did not increase the risk of metastasis or survival. Choroidal melanomas are both radioresistant and located close to visual structures (the optic nerve and macula) of the eye, which may be preserved in some settings without compromising tumor control, as this is the first priority. Different types of radiation therapy may be used for such tumors: brachytherapy and charged particles, including proton beam therapy. If visual prognosis is dependent to the local treatment, the vital prognosis is dependent on the metastatic risk, with a risk of liver involvement in 20 to 50% of patients, depending on tumor size and genomics. Median survival after the discovery of liver metastases is about 15 months. The management of these patients is often complex. Systemic therapies (chemotherapy, targeted therapies, immunotherapy, etc.) yield limited response rates and although local treatments of liver metastases are promising, they are only feasible in selected patients. The mission of the MELACHONAT national network is to improve the management of patients regardless of the stage of the disease. The patient association ANPACO is dedicated to help uveal melanoma patients in their health care path and to promote knowledge dissemination within the patient community. The aim of this review is to focus on the local treatments of uveal melanomas as well as the management of their metastatic evolution.


Derivation of a Performance Checklist for Ultrasound-Guided Arthrocentesis Using the Modified Delphi Method.
Arthrocentesis is an important skill for physicians in multiple specialties. Recent studies indicate a superior safety and performance profile for this procedure using ultrasound guidance for needle placement, and improving quality of care requires a valid measurement of competency using this modality. We endeavored to create a validated tool to assess the performance of this procedure using the modified Delphi technique and experts in multiple disciplines across the United States. We derived a 22-item checklist designed to assess competency for the completion of ultrasound-guided arthrocentesis, which demonstrated a Cronbach's alpha of 0.89, indicating an excellent degree of internal consistency. Although we were able to demonstrate content validity for this tool, further validity evidence should be acquired after the tool is used and studied in clinical and simulated contexts.


Genetic basis of ultraviolet-B effects on contact hypersensitivity.
The genetic basis of the effects of ultraviolet B (UVB) radiation on the induction of contact hypersensitivity (CH) to dinitrofluorobenzene (DNFB) has been explored in genetically defined mice. It was found that acute, low-dose UVB radiation produced profound depletion of epidermal Langerhans cells (LC) at UVB-treated sites in all strains of mice tested. However, when DNFB was applied to UVB radiation sites, unresponsiveness developed in some strains of mice, but vigorous contact hypersensitivity was induced in others. The UVB-susceptible phenotype proved dominant or codominant in F1 hybrids derived from parental strains of the susceptible and UVB-resistant phenotypes. Experiments conducted in one set of F1 hybrids derived from two UVB-susceptible parental strains displayed UVB resistance, suggesting gene complementation, and showed that more than one genetic locus was involved. Segregant backcross populations, analyzed for the capacity to develop CH after UVB treatment and skin painting with DNFB, revealed that at least two, and probably three, independent genetic loci participate in determining UVB resistance. Results of experiments with H-2 congenic and recombinant mice derived from the B10 background implicated class I genes of the major histocompatibility complex as relevant genetic factors. These results indicate that there is a dissociation between the effects of UVB radiation on epidermal Langerhans cells and the capacity of a cutaneous surface to support the induction of contact hypersensitivity. The data indicate that the induction of CH to haptens is dependent on normal numbers of functional LC at the skin painting site only in some strains of mice. The data imply that in the so-called UVB-resistant strains of mice, alternative (non-Langerhans cell-dependent) mechanisms allow for the induction of CH. Several independent genetic loci, one of which appears to be H-2, govern this UVB-related effect.


AAV-Mediated Gene Transfer to Dorsal Root Ganglion.
Transferring genetic molecules into the peripheral sensory nervous system to manipulate nociceptive pathophysiology is a powerful approach for experimental modulation of sensory signaling and potentially for translation into therapy for chronic pain. This can be efficiently achieved by the use of recombinant adeno-associated virus (rAAV) in conjunction with nociceptor-specific regulatory transgene cassettes. Among different routes of delivery, direct injection into the dorsal root ganglia (DRGs) offers the most efficient AAV-mediated gene transfer selectively into the peripheral sensory nervous system. Here, we briefly discuss the advantages and applications of intraganglionic microinjection, and then provide a detailed approach for DRG injection, including a list of the necessary materials and description of a method for performing DRG microinjection experiments. We also discuss our experience with several adeno-associated virus (AAV) options for in vivo transgene expression in DRG neurons.


Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ induced diabetic rats.
Diabetes mellitus (DM) is a cluster of metabolic diseases that exhibits high blood glucose levels accompanied by hyperlipidemia and inflammation. DM is the primary risk factor contributes majorly to cardiovascular disease (CVD) mediated morbidity and mortality. The incidence of dyslipidemia seems to attribute considerably to the initiation of CVDs. The beneficial action of isoquercetin on hyperlipidemia and related signaling pathways are not documented yet, hence we decide to carry out this study. The experimental rats were divided into five groups: Group 1, control rats; group 2, isoquercetin control (40 mg/kg b.w); group 3, diabetic rats (STZ-40 mg/kg b.w); group 4, diabetic + isoquercetin (40 mg/kg b.w); and group 5, diabetic + glibenclamide (600 µg/kg b.w). The animals were sacrificed at the end of the experimental duration of 45 days. Results of our analysis reveal that isoquercetin have a major impact on the tissue lipid profile, isoquercetin strongly regulates the expression of various lipid-metabolizing enzymes, C-reactive protein, expression of various inflammatory genes, SREBP-1C genes and proteins and AMP-activated protein kinase-α (AMPK) signaling pathway genes and proteins. Results recommend that isoquercetin can be effective in mitigating the consequences of hyperlipidemia and DM.


Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms.
Tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are significantly elevated in patients with congestive heart failure (CHF). Pentoxifylline, a xanthin-derived agent, is known to inhibit the production of TNF-alpha and IL-6. Recent studies have shown that pentoxifylline produces an increase in ejection fraction, a decrease in left-ventricular chamber size and an improvement in clinical status in patients with idiopathic-dilated cardiomyopathy. Therefore, we studied the effects of pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy. Primary endpoint was left-ventricular ejection fraction (LVEF) assessed by contrast 2D echocardiography. Secondary endpoints were concentrations of TNF-alpha, IL-6, brain natriuretic peptide, maximal oxygen uptake (VO(2 max)) assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire score or New York Heart Association scale. Forty-seven patients (31.9% ischemic, 21.3% hypertensive, 10.6% ischemic and hypertensive, 36.2% idiopathic-dilated cardiomyopathy) were randomly assigned to pentoxifylline 600 mg BID (n=23) or placebo (n=24) if they had a compensated CHF with a LVEF less than or equal to 40% and had taken their standard treatment consisting of angiotensin-converting enzyme inhibitors, diuretics and beta-blockers for at least 3 months. Baseline demographic and clinical characteristics of each group were similar. Forty-one patients completed the study protocol and were analysed for primary and secondary endpoints. After 6 months of treatment, LVEF was unchanged in the pentoxifylline group compared with placebo (29+/-7 to 33+/-10% vs. 27+/-9 to 34+/-9%, respectively, P=NS). Also the secondary endpoints did not significantly change during follow-up. Additional treatment with pentoxifylline is neutral with regard to left-ventricular function, inflammatory cytokines and symptoms in patients with ischemic, hypertensive and idiopathic-dilated cardiomyopathy.


Feasibility and initial results of percutaneous aortic valve implantation including selection of the transfemoral or transapical approach in patients with severe aortic stenosis.
The purpose of this study was to evaluate the feasibility and initial results of a multidisciplinary percutaneous aortic valve implantation (PAVI) program including the transfemoral approach (TFA) and the transapical approach (TAA). This was a prospective registry including all patients with symptomatic severe aortic stenosis who were evaluated for PAVI and those who finally underwent the procedure. All patients were considered very high risk or nonsurgical candidates, and an algorithm based on prespecified criteria was used to determine the most appropriate approach (TFA vs TAA) for each patient. The Edwards-Sapien valve was used in all cases, and all procedures were performed without cardiopulmonary bypass. A total of 29 consecutive patients were evaluated for PAVI, and 22 of them underwent the procedure (mean age 84 +/- 7 years, predicted surgical mortality 26 +/- 16%), with 11 patients selected for each approach. Reasons for selecting TAA rather than TFA were the following: small diameter and/or severe calcification of the iliofemoral arteries (4 patients), peripheral vascular disease (4 patients), porcelain aorta (2 patients), and horizontal ascending aorta (1 patient). Successful aortic valve implantation was obtained in 91% of the procedures, and procedural and 30-day mortality were 4.3% and 8.7%, respectively. There were no cases of myocardial infarction, vascular complications, or cerebrovascular accident. PAVI was associated with a significant reduction in mean aortic gradient (baseline 34 +/- 10 mm Hg, postprocedure 9 +/- 3 mm Hg, p <0.001), with no cases of severe aortic regurgitation. After a median follow-up period of 6 months, there were no additional major adverse cardiac events, and no significant changes in hemodynamic aortic valve parameters were observed. In conclusion, this study demonstrates the feasibility and low complication rate of a PAVI program using a prospective strategy for the selection of the TFA or TAA, with half of the patients selected for each approach.


The regional variation of denitrification phenotypes under anoxic incubation with soils from eight forested catchments in different climate zones of China.
Denitrification characteristics of forest soils from eight headwater catchments in China were investigated in this study, along a climatic gradient from the tropics in the South to the temperate zones. Within each catchment, different landscape positions along hydrological flow paths were also considered, including well-drained soils on hill slopes and poorly drained soils in groundwater discharge zones. The results showed that instantaneous denitrification rates were much greater in soils from the northern sites than those from the southern sites (with the average of 110.0 and 25.4nmolNg-1drysoilh.-1, respectively). Large potentials for nitrous oxide (N2O) loss (evaluated as maximum N2O accumulation before it was reduced to dinitrogen (N2)) were observed in the six tropical and subtropical catchments, particularly in soils with high carbon (C) and nitrogen (N). Meanwhile high N2O/(N2O+N2) stoichiometries were displayed in soils from these southern sites. Within catchments, soils from the groundwater discharge zones showed greater potential denitrification rates but smaller N2O/(N2O+N2) ratios in comparison with those on the hill slopes, implying large N removal potentials of soils from the groundwater discharge zones. Furthermore, our findings suggest soil pH is the key controller for the potential denitrification rates and the N2O/(N2O+N2) stoichiometries. Soil pH, C and N availability affect the potential for N2O loss synergistically. Our findings not only pinpoint the denitrification phenotypes of soils along the climatic gradient, but also confirm the small-scale variations within catchments which reflect the in situ habitat of the denitrifiers. These indicate the importance of discrimination related to different landscape positions when modeling N2O emissions and N removals from regional N loading.


Neurasthenia and related problems.
Neurasthenia is a diagnostic entity included in ICD-9 which is used in daily clinical practice in China and the Soviet Union, as well as some other Asian countries, so far as I know. Although it was eliminated from the psychiatric nosology in DSM-III of the United States and in several European countries, this disease has not disappeared. In my view, elimination of the category only indicates change of diagnostic concept without definite direction. Whether this change will be accepted by psychiatrists all over the world is still a question. The continued use of this diagnostic term in China is justifiable, I believe. The final resolution of these differences in views and practice remains for future development in psychiatric science.


Development of an integrated electrochemical biosensor for sucrose and its implementation in a continuous flow system for the simultaneous monitoring of sucrose, fructose and glucose.
An integrated amperometric sucrose biosensor involving a 3-mercaptopropionic acid (MPA) self-assembled monolayer (SAM)-modified gold disk electrode (AuE) and coimmobilization of the enzymes invertase (INV) and fructose dehydrogenase (FDH) as well as the redox mediator tetrathiafulvalene (TTF) by means of a dialysis membrane is reported. Amperometry in stirred solutions at a detection potential of +0.10 V provided a linear calibration plot for sucrose over the 1.2 × 10(-6)-3.0 × 10(-3) mol L(-1) concentration range, with a limit of detection of 3.6 × 10(-7) mol L(-1). The practical usefulness of the biosensor was demonstrated by determining sucrose in condensed milk and in an infant food reference material with good results. Additionally, the biosensor was implemented together with commercial fructose and glucose amperometric biosensors in a continuous flow system to perform the multiplexed quantification of sucrose, fructose and glucose in a single experiment. The operational characteristics of the biosensors in this novel flow system were evaluated and their applicability was demonstrated through the simultaneous determination of the three sugars in the above-mentioned reference material.


Diversity of circulating rotavirus strains in children hospitalized with diarrhea in India, 2005-2009.
India accounts for 22% of the 453,000 global rotavirus deaths among children <5 years annually. The Indian Rotavirus Strain Surveillance Network provides clinicians and public health partners with valuable rotavirus disease surveillance data. Our analysis offers policy-makers an update on rotavirus disease burden with emphasis on regional shifts in rotavirus strain epidemiology in India. Children <5 years requiring hospitalization for acute gastroenteritis were selected from 10 representative hospitals in 7 cities throughout India between November 2005 through June 2009. We used a modified World Health Organization protocol for rotavirus surveillance; stool specimens were collected and tested for rotavirus using enzyme immunoassay and reverse-transcription polymerase chain reaction. A total of 7285 stool specimens collected were tested for rotavirus, among which 2899 (40%) were positive for rotavirus. Among the 2899 rotavirus detections, a G-type could not be determined for 662 (23%) and more than one G type was detected in 240 (8%). Of 1997 (69%) patients with only one G-type, the common types were G1 (25%), G2 (21%), G9 (13%), and G12 (10%). The proportion of rotavirus infections attributed to G12 infections rose from 8% to 39% in the Northern region and from 8% to 24% in the Western region. This study highlights the large, ongoing burden of rotavirus disease in India, as well as interesting regional shifts in rotavirus strain epidemiology, including an increasing detection of G12 rotavirus strains in some regions. While broad heterotypic protection from rotavirus vaccination is expected based on pre- and post-licensure data from other settings, effectiveness assessments and rotavirus strain monitoring after vaccine introduction will be important.


Sex-Specific Wolbachia Infection Patterns in Populations of Polygraphus proximus Blandford (Coleoptera; Curculionidae: Scolytinae).
Wolbachia symbionts are maternally inherited bacteria that are widely distributed among Arthropoda hosts. Wolbachia influence their host biology in diverse ways. They may induce reproductive abnormalities, protect hosts against pathogens and parasites, or benefit hosts through metabolic provisioning. The progeny of an infected female are ordinarily infected with Wolbachia; however, Wolbachia have no future in male host progeny because they cannot transmit the symbiont to the next generation. Here, we analyze native and invasive populations of the four-eyed fir bark beetle (Polygraphus proximus) for Wolbachia prevalence and symbiont genetic diversity. This species is a dangerous pest of Siberian fir (Abies sibirica) forests. The native range of P. proximus includes the territories of the Russian Far East, Japan, Korea, and Northeast China, whereas its invasive range includes West Siberia, with further expansion westward. Surprisingly, we revealed a difference in the patterns of Wolbachia prevalence for males and females. Infection rate and Wolbachia titers were higher in females than in males. ST-533, the only haplotype of Wolbachia supergroup B, was associated with a minimum of three out of the five described mitochondrial haplotypes.


PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity.
MicroRNAs fine-tune gene expression by inhibiting the translation of mRNA targets. Argonaute (Ago) proteins are critical mediators of microRNA-induced post-transcriptional silencing and have been shown to associate with endosomal compartments, but the molecular mechanisms that underlie this process are unclear, especially in neurons. Here, we report a novel interaction between Ago2 and the BAR-domain protein, PICK1. We show that PICK1 promotes Ago2 localization at endosomal compartments in neuronal dendrites and inhibits Ago2 function in translational repression following neuronal stimulation. We propose that PICK1 provides a link between activity-dependent endosomal trafficking and local regulation of translation in neurons.


Facilitation of the expression but not the acquisition of latent inhibition by haloperidol in rats.
In the latent inhibition (LI) paradigm, nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus. The administration of haloperidol in both the preexposure and the conditioning stages was found to enhance LI in the conditioned emotional response (CER) procedure (Weiner and Feldon, 1986). The present experiments investigated the effects of 0.1 mg/kg haloperidol administration on LI in a two-way avoidance procedure, consisting of two stages: preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; and conditioning, in which the animals acquired a two-way avoidance response with the tone serving as the warning signal. Experiments 1 and 2 tested whether the administration of haloperidol confirmed to the preexposure stage, where learning to ignore the nonreinforced stimulus takes place, would suffice to enhance the LI effect. In Experiment 1, preexposure and conditioning were conducted 24 hr apart. LI was obtained in both the placebo and haloperidol conditions, but the effect was not more pronounced under the drug. In addition, haloperidol-treated animals exhibited impaired avoidance performance. In Experiment 2, preexposure and conditioning were given 72 hr apart. With this interval, haloperidol did not affect avoidance performance. However, also under these conditions, the magnitude of the LI effect was not larger in the haloperidol-treated groups, indicating that the administration of the drug in the preexposure stage alone did not suffice to enhance LI.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of domains influencing assembly and ion channel properties in alpha 7 nicotinic receptor and 5-HT3 receptor subunit chimaeras.
Nicotinic acetylcholine receptors (nAChRs) and 5-hydroxytryptamine type 3 receptors (5-HT(3)Rs) are members of the superfamily of neurotransmitter-gated ion channels. Both contain five subunits which assemble to form either homomeric or heteromeric subunit complexes. With the aim of identifying the influence of subunit domains upon receptor assembly and function, a series of chimaeras have been constructed containing regions of the neuronal nAChR alpha 7 subunit and the 5-HT(3) receptor (3A) subunit. A series of subunit chimaeras containing alpha 7 and 5-HT(3A) subunit domains have been constructed and expressed in cultured mammalian cells. Properties of the expressed receptors have been examined by means of radioligand binding, agonist-induced changes in intracellular calcium and patch-clamp electrophysiology. Subunit domains which influence properties such as rectification, desensitization and conductance have been identified. In addition, the influence of subunit domains upon subunit folding, receptor assembly and cell-surface expression has been identified. Co-expression studies with the nAChR-associated protein RIC-3 revealed that, in contrast to the potentiating effect of RIC-3 on alpha 7 nAChRs, RIC-3 caused reduced levels of cell-surface expression of some alpha 7/5-HT(3A) chimaeras. Evidence has been obtained which demonstrates that subunit transmembrane domains are critical for efficient subunit folding and assembly. In addition, functional characterization of subunit chimaeras revealed that both extracellular and cytoplasmic domains exert a dramatic and significant influence upon single-channel conductance. These data support a role for regions other than hydrophobic transmembrane domains in determining ion channel properties.


Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas.
Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a key role in responses to hypoxia and expression of HIF-1alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1alpha expression in gastric carcinoma. We examined HIF-1alpha, vascular endothelial growth factor (VEGF), and insulin-like growth factor-2 (IGF-2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF-1alpha expression, clinicopathological features, and survival were examined. HIF-1alpha expression correlated with tumor size (P<0.005), depth of invasion (P=0.018), VEGF expression (P=0.03), and intra-tumor MVD (P<0.005). IGF-2 expression was more prevalent in HIF-1alpha positive than in HIF-1alpha negative tumors and the 5-year survival rate was 58.4% for HIF-1alpha positive patients and 81.5% for HIF-1alpha negative patients (P=0.009). HIF-1alpha expression is an independent prognostic factor in gastric carcinoma (P=0.032). Overexpression of HIF-1alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.


Chronic opioid use before and after exercise therapy and patient education among patients with knee or hip osteoarthritis.
To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use. In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations. We found a 10% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population. Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account.


Inhibition of proliferation and induction of differentiation of human and mouse myeloid leukemia cells by new ethyleneglycol-type nonphosphorus alkyl ether lipids.
A variety of ethyleneglycol-type nonphosphorus alkyl ether lipids, ether derivatives of diethyleneglycol in which the two hydroxyl groups were substituted with long chain alkyl and quaternary ammonioalkyl groups, were synthesized and their effects on proliferation and differentiation of cultured human (HL-60) and mouse (M1) myeloid leukemia cells were studied. Incubation with these compounds inhibited the cellular proliferation, and the cells differentiated into morphologically and functionally mature granulocytes. Of the compounds tested, 1-[2-[2-(octadecyloxy)ethoxy]ethoxy]-butylpyridinium mesylate (EG-6) was the most effective in inducing differentiation of HL-60 cells. Almost maximal induction of differentiation and inhibition of growth of HL-60 cells on day 6 were observed when the cells were treated with EG-6 for 1 day and then cultured without EG-6 for a further 5 days. The inhibitory effect of EG-6 on the leukemic cells was over 100 times more than that of 2-[2-(dodecyloxy)ethoxy]ethyl 2-pyridinioethyl phosphate, a potent antileukemic ether phospholipid.


Regional cerebral blood flow in hemiparkinsonian patients. Emission computerized tomography of inhaled 133Xenon before and after levodopa.
Regional and mean cerebral blood flow (rCBF, CBF) were measured by tomography of inhaled 133Xe in 18 hemiparkinsonian patients before and after levodopa (L-dopa). Baseline mean CBF was 55 ml/ (100 g X min) after an L-dopa-free interval of at least 10 h (range 10-13) and remained unchanged at 56.1 ml/ (100 g X min) after optimal clinical improvement was achieved by L-dopa. However, L-dopa reduced rCBF significantly (P less than 0.05) in the striatum contralateral to the symptomatic limbs. In patients with adverse reactions such as hyperkinesias and on/off symptoms, flow tended to increase bilaterally in striatum and often markedly in midline structures anatomically related to globus pallidus and thalamus. Compared with a normal population, the subcortical rCBF distribution was asymmetrical with a reduced flow (-18%) in the striatum contralateral to the symptomatic limbs and in midline structures anatomically related to globus pallidus and thalamus (-12%). Cortical CBF was inverse related to the duration of Parkinson's disease (P less than 0.05), probably reflecting an increasing mental deterioration with time.


Microbiological and serological studies on caprine pneumonias in Oman.
Eight of 10 typical cases of contagious caprine pleuro-pneumonia in Oman yielded strain F38-like mycoplasmas from the lungs in high titre, but no other mycoplasmas: both negative animals had been treated with tylosin shortly before death. Among 21 other lungs examined three of six cases of acute pneumonia yielded Mycoplasma ovipneumoniae; one also yielded M capricolum. M ovipneumoniae was also isolated from all eight cases of chronic pneumonia sampled from an abattoir, and from the lungs of three animals which died without overt signs of pneumonia. A single isolate of M arginini and three of unidentified mycoplasmas were also obtained from goats with and without pneumonia. Various bacterial species were isolated, none of which predominated. Antibodies to M mycoides subspecies capri (M m capri) and strain F38 were detected in sera from eight different sources. Assuming titres of 1 in 40 or more as positive in the indirect haemagglutination test used, 29 per cent of 422 serum samples had antibodies to M m capri alone, 2.6 per cent to strain F38 alone and 3.6 per cent to both organisms. These results confirm the presence of F38-like mycoplasmas in Oman, and indicate also widespread infection with M m capri. The role of the latter in caprine pneumonias in Oman requires elucidation.


MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90.
The MUC1 heterodimeric transmembrane glycoprotein is aberrantly overexpressed by most human carcinomas. The MUC1 C-terminal subunit localizes to mitochondria and blocks stress-induced activation of the intrinsic apoptotic pathway. How MUC1 is delivered to mitochondria is not known. The present studies demonstrate that MUC1 forms intracellular complexes with HSP70 and HSP90. We show that the MUC1 cytoplasmic domain binds directly to HSP70 in vitro. By contrast, binding of MUC1 to HSP90 in vitro is induced by c-Src-mediated phosphorylation of the MUC1 cytoplasmic domain. c-Src also increases binding of MUC1 to HSP90 in cells. In concert with these results, we show that heregulin (HRG), a ligand for ErbB receptors, activates c-Src and, in turn, stimulates binding of MUC1 to HSP90. We also show that inhibitors of c-Src or HSP90 block HRG-induced targeting of MUC1 to mitochondria and integration of MUC1 into the mitochondrial outer membrane. These findings indicate that MUC1 is delivered to mitochondria by a mechanism involving activation of the ErbB receptor-->c-Src pathway and transport by the molecular chaperone HSP70/HSP90 complex.


Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids.
A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.


Extracorporeal membrane oxygenation for the treatment of massive pulmonary embolism. An analysis of the ELSO database.
Extracorporeal membrane oxygenation (ECMO) may be beneficial in treatment of massive pulmonary embolus (PE), however the current evidence to guide its use is limited. We aimed to compare the incidence, characteristics, treatments, and outcomes of patients with massive PE by mode of ECMO from a large international registry. Retrospective observational study of the Extracorporeal Life Support Organization (ELSO) database. A total of 821 patients underwent 833 ECMO episodes for PE. Mean age was 49 (±15) years, 408 (50.1%) were female, and 450 (54.7%) had a cardiac arrest prior to ECMO initiation. Venoarterial (VA) ECMO was the most common mode in 489 (58.7%), followed by extracorporeal cardiopulmonary resuscitation (ECPR) in 229 (27.4%) and venovenous (VV) ECMO in 85 (10.2%). The number of episodes per year increased over the study period, predominantly driven by an increase in ECPR. In-hospital mortality was the highest for ECPR 156/229 (68.1%), followed by VA ECMO 209/498 (42.7%) and VV ECMO 24/85 (28.2%) P < 0.001. After controlling for univariate and clinically significant variables at the time of ECMO initiation, increasing age (OR 1.02 (1.00-1.03), lower pH (OR 0.18 (0.03-0.44), lower diastolic blood pressure (OR 0.99 (0.97-1.00) and ECPR mode (OR 3.67 (1.46-9.230) were independently associated with in-hospital mortality. ECMO use for massive PE is increasing globally, and overall mortality rates compare favorably with other indications of ECMO. The use of ECPR and worsening metabolic status at initiation were associated with higher in-hospital mortality, suggesting delays in initiating ECMO should be avoided.


Multimodal multidisciplinary standardization of perioperative care: still a long way to go.
The complexity of the perioperative care process has resulted in a suboptimal use of resources, quality problems and a relatively high incidence of errors. In an attempt to optimize resources, patient safety, and quality, multimodal, multidisciplinary standardization of the care process has become an increasingly recognized goal. The anaesthesiologist as perioperative clinician plays a pivotal role in the development and implementation of standardized perioperative care. Historically, however, a significant portion of perioperative care has relied upon anecdotal information that represents an amalgam of any individual anaesthesiologist's collective influences and experiences. Current status of standardized perioperative care and different factors that influence successful implementation of guidelines, fast track surgery programs and clinical pathways are described. Although recent literature indicates that standardization of perioperative care improves efficiency, quality, and patient satisfaction, implementation of standardized care is difficult since resistance is still enormous.


p-Chloro-diphenyl diselenide modulates Nrf2/Keap1 signaling and counteracts renal oxidative stress in mice exposed to repeated dexamethasone administrations.
Dexamethasone is a synthetic glucocorticoid that has been associated with oxidative stress in central and peripheral tissues. p-Chloro-diphenyl diselenide ((p-ClPhSe)2) is an antioxidant organoselenium compound. The present study evaluated whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1) signaling contributes to the (p-ClPhSe)2 antioxidant effects in the kidney of mice exposed to dexamethasone. Adult Swiss mice received dexamethasone (intraperitoneal) at a dose of 2 mg/kg or its vehicle for 21 days. After that, mice were treated with (p-ClPhSe)2 (intragastric) (1, 5, or 10 mg/kg) for 7 days. Samples of kidneys were collected for biochemical assays. (p-ClPhSe)2 at a dose of 1 mg/kg reversed the renal reactive oxygen species (ROS) and carbonyl protein (CP) levels increased by dexamethasone. (p-ClPhSe)2 at doses of 5 and 10 mg/kg was effective against the increase of thiobarbituric acid reactive substances, ROS, and CP, as well as the decrease of δ-aminolevulinic acid dehydratase activity and nonprotein sulfhydryl levels induced by dexamethasone. At 5 mg/kg, (p-ClPhSe)2 reduced the renal levels of 4-OH-2-HNE and heme oxygenase (HO-1), as well as modulated the Nrf2/Keap-1 signaling in mice exposed to dexamethasone. The present findings revealed that (p-ClPhSe)2 antioxidant effects were associated with the modulation of Nrf2/Keap-1 signaling pathway in the kidney of mice exposed to dexamethasone.


Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects.
To assess the effect of green tea intake on the pharmacokinetics of the β-blocker celiprolol. In an open-label crossover study, 3 healthy subjects were given water or a green tea beverage daily for 3 days. On day 4, each subject received a single oral dose of 200 mg celiprolol with water or green tea. Serum and urinary concentrations of celiprolol were measured for up to 24 hours. Green tea intake decreased the area under the serum concentration-time curve and urinary excretion of celiprolol by 98.6 and 98.0%, respectively. Green tea intake might have a negative impact on the clinical effectiveness of celiprolol.


Prevention and treatment of chronic heart failure through traditional Chinese medicine: Role of the gut microbiota.
In recent years, although the concept and means of modern treatment of chronic heart failure(CHF) are continually improving, the readmission rate and mortality rate are still high. At present, there is evidence that there is a link between gut microbiota and heart failure, so the intervention of gut microbiota and its metabolites is expected to become a potential new therapeutic target in heart failure. Traditional Chinese medicine(TCM) has apparent advantages in stabilizing the disease, improving heart function, and improving the quality of life. It can exert its effect by operating in the gut microbiota and is an ideal intestinal micro-ecological regulator. Therefore, this article will mainly discuss the advantages of traditional Chinese medicine in treating CHF, the relationship between traditional Chinese medicine and gut microbiota, the relationship between CHF and gut microbiota, and the ways of regulating gut microbiota by traditional Chinese medicine to prevent and treat CHF. It will specify the target and mechanism of traditional Chinese medicine treating heart failure by acting gut microbiota and provide ideas for the treatment of heart failure.


Relationships of working status and cardiac capacity to functional age before and after coronary bypass surgery.
In 77 patients having coronary bypass surgery, we evaluated the interaction between chronological age, functional age, and working status pre- and postoperatively. Preoperatively the chronological age of those not working compared to those working was 60.7 +/- 8.4 years versus 53.0 +/- 8.3 years (P less than 0.001). The preoperative functional ages were 93.5 +/- 11.5 versus 87.6 +/- 10.9 years (P less than 0.05). Postoperatively no patient who was not working preoperatively started work, although functional age improved from 93.5 +/- 11.5 to 83.2 +/- 12.8 years (P less than 0.001). Postoperatively subjects who stopped working showed similar improvement in maximal cardiac output, and maximal oxygen consumption compared to those who continued working; however, the functional age after surgery was 80.6 +/- 9.4 versus 69.6 +/- 11.6 years (P less than 0.01). This study showed a poor relationship between degree of improvement in cardiac function after bypass surgery and change in working status. However, functional age and chronological age contribute to the poor results with regard to return to work.


Visuomotor therapy modulates corticospinal excitability in patients following anterior cruciate ligament reconstruction: A randomized crossover trial.
Corticospinal adaptations have been observed following anterior cruciate ligament reconstruction around the time of returning to activity. These measures have been related to quadriceps strength deficits. Visuomotor therapy, combining motor control tasks with visual biofeedback, has been shown to increase corticospinal excitability. The purpose of this study was to assess the immediate changes of corticospinal excitability following a single session of visuomotor therapy in patients following anterior cruciate ligament reconstruction. This was a single blinded, sham-controlled crossover study. Ten patients following ACLR (8 Female, 26.1(6.2) years) completed assessments of quadriceps strength at approximately 4- and 6-months following anterior cruciate ligament reconstruction. At 6-months, quadriceps motor evoked potentials were assessed at 80%, 90%, 100%, 110%, 120%, 130%, 140%, and 150% of the patient's active motor threshold. Patients were randomized to receive a single session of visuomotor therapy(active) or passive motion(sham). Quadriceps motor evoked potentials were reassessed for treatment effect. Following a one-week washout period, all patients received the crossover intervention. Moderate to large increases in motor response following visuomotor therapy 90%(P = .008, r = 0.60), 110%(P = .038, r = 0.46), 120%(P = .021, r = 0.52), 130%(P = .021, r = 0.52), 140%(P = .008, r = 0.60) and 150%(P = .021, r = 0.52) of the active motor threshold were found. Moderate increases in motor response was observed following the passive motion at 80% of the active motor threshold(P = .028, r = 0.49). A single session of visuomotor therapy was found to increase quadriceps corticospinal motor response greater than the response to sham therapy. Visuomotor therapy is a potential supplement to quadriceps rehabilitation programs when upregulation of corticospinal excitability is indicated.


Hypertrophic cardiomyopathy and other causes of sudden cardiac death in young competitive athletes, with considerations for preparticipation screening and criteria for disqualification.
Cardiovascular disease is the most frequent cause of death in young athletes, and hypertrophic cardiomyopathy (HCM) is the single most common condition responsible for these tragedies. Detection of diseases such as HCM can be achieved in general athlete populations through preparticipation screening, and most effectively if testing with electrocardiography or echocardiography is incorporated into the process. Criteria for disqualification and eligibility, based on identified cardiovascular abnormalities, are available in consensus panel guidelines for both United States and European athletes. Removal from intense training and competition is recommended for athletes with HCM, some of whom may ultimately be judged to be at unacceptably high risk for sudden death and eligible for prophylactic defibrillator implantation.


Epidemiology and phenotype of congenital coronary artery anomalies. Analysis of 80 cases found in necropsies of stillborn fetuses and infants.
In the period from 1961 to 1974, 80 cases of congenital coronary artery anomalies in necropsies of infants and stillborn fetuses were diagnosed in the Czech Socialist Republic among more than 2.1 million consecutive deliveries. In the population thus defined the mean frequency of these anomalies was 3.8 per 100,000, with extreme values from 1.3 to 7.0 per 100,000. The epidemiological and clinical phenomena of these anomalies and their relations to selected biological-genetic and ecological factors are discussed.


PHI stimulates intestinal fluid secretion.
Regulatory peptides are likely to have a role in the control of net intestinal fluid transport. PHI is a peptide recently isolated from porcine duodenum which has been shown to have sequence homologies with other peptides of the glucagon-secretin family. We have studied the effect of intravenous infusion of synthetic PHI on net intestinal fluid transport in the rat small intestine. During PHI infection net absorption was reduced in the duodenum and jejunum and net secretion was observed in the ileum. Thus synthetic PHI appears to be capable of strongly stimulating intestinal secretion in the rat.


Effect of ligand on particle size and morphology of nanostructures synthesized by thermal decomposition of coordination compounds.
Thermal decomposition of organometallic and various coordination compounds are known as general method to synthesize a wide range of nanostructures including metals, metal oxides and sulfides. Herein, in order to coordinate metals and prepare suitable precursor - due to the efficient role of precursor on the particle size and morphology of products - appropriate ligands will be introduced.


Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase.
Wortmannin is a fungal metabolite that so far has been shown to act as a selective inhibitor of phosphoinositide 3-kinase. It can therefore be used to investigate the convergence between two major cellular signalling systems: those involving G-protein-coupled receptors and those involving receptor tyrosine kinases. Importantly, wortmannin can enter intact cells, making whole-cell studies of the above signalling pathways possible.


Monitoring retinoschisis and non-acute retinal detachment by optical coherence tomography: morphologic aspects and clinical impact.
To differentiate retinoschisis (RS) from non-acute retinal detachment (naRD) in clinical routine using optical coherence tomography (OCT), describe unique morphological OCT characteristics and monitor disease progression. This prospective, observational study included 64 eyes of 44 patients with either RS or naRD. Patients were examined clinically and using Heidelberg Spectralis OCT® , Topcon DRI OCT® and Cirrus HRA-OCT® over 2 years with follow-up at 1, 3, 6, 12 and 24 months. Main outcomes were typical morphologic findings of RS and naRD described in OCT. Progression was monitored using Spectralis OCT® follow-up mapping and an eye-tracking method. Forty-seven eyes were diagnosed with RS and 17 with naRD. Optical coherence tomography (OCT) provided a definite diagnosis in four eyes diagnosed clinically as uncertain. Seventy-seven percentage of eyes with RS were atrophic in the inner leaf (IL), whereas 41% with naRD showed cystoid alteration. A discontinuation of the IL clinically observed as an inner-layer break (ILB) could be imaged. We described a tissue retraction within the outer leaf (OL), which corresponded to outer-layer breaks (OLBs) in clinical examinations in nine eyes (19%). Optical coherence tomography (OCT) is a reliable method to differentiate and monitor RS from naRD. Morphological characteristics, including ILB and OLB, could be accurately illustrated in RS.


Antibody as immunological probe for studying refolding of bovine serum albumin. Refolding within each domain.
Antiserum to bovine serum albumin was fractionated into populations of antibody directed against party, an apparent pathway of refolding within each domain was obtained which is consistent with the proposed evolutionary pathway of the albumin molecule. The COOH-terminal one-third of each domain refolds faster than the NH2-terminal two-thirds of each respective domain. In addition, further evidence in given for a correlation between the rate of refolding and the degree of interdomain influence that might restrict refolding.


Mechanisms mediating the vasodilatory effects of juglone in porcine isolated coronary artery.
Juglone (5-hydroxy-1, 4-naphthoquinone), is a natural phenolic compound that has been shown to relax smooth muscle. Therefore the aim of this study was to determine the effect of juglone on vascular tone using porcine coronary artery (PCA). Segments of PCA, with or without endothelium, were mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane A2 analog U46619 or KCl. After pre-contraction, cumulative concentrations of juglone were added to the tissues, in the presence or absence of a variety of inhibitors on intracellular signaling pathways. Juglone (10-9 to 10-5 M) produced a concentration-dependent relaxation of the PCA which was reduced in endothelium-denuded vessels, as well as in vessels pre-treated with the nitric oxide synthase inhibitor L-NAME, indicating that at least part of the effect of juglone is mediated through an endothelium, NO-dependent mechanism. Juglone also inhibited contractions in response to influx of extracellular calcium and release of intracellular calcium, indicating that juglone may inhibit a common signaling pathway downstream of calcium. Contractions to the protein kinase C activator Phorbol 12-myristate 13-acetate were also reduced by juglone, suggesting that juglone might be acting through inhibition of protein kinase C. In summary, juglone produces a relaxation of the porcine coronary artery through activation of the nitric oxide pathway and inhibition of calcium-induced contractions.


Evidence-based practical guideline for procedural pain management and sedation for burn pediatrics patients undergoing wound care procedures.
Almost all children with burns experience pain as a result of a complex pathophysiologic process that is usually untreated, and up to 38% of all pediatric burn victims develop anxiety disorders due to pain after hospital admission. Hence, it is important to manage pain and anxiety in the care of burn victim children. The goal of this review was to develop an evidence-based guideline for procedural pain management and sedation for burned children undergoing wound care procedures. The review was reported according to Reporting Items for practice Guidelines in Healthcare (RIGHT) protocol. A search of literature was done from Cochrane review, PubMed, Google Scholar, Embase, web of science and Hinari database key words "pediatrics", "children", "burn", "procedural wound care", "wound dressing", "non-pharmacological", "analgesia", "pain management" and "sedation" were used. Extraction and filtering of the results was determined based on the interventions, outcome, population, and methodological quality, and inclusion and exclusion criteria. Finally, 6 systematic review and meta-analysis, 1observational study, and 16 randomized control trial Studies were appraised for quality, and conclusion was made based on their level of evidence and grade of recommendation. For effective management of procedural pain and accompanying anxiety during WCP in children, we recommend using non-pharmacological strategies as an adjunct with calculated dose of analgesics based on the children's analgesic requirements. We also recommend ketamine-dexmedetomidine as an effective first-line analgesic-sedation, and ketamine-propofol, propofol-remifentanil, propofol-fentanyl, and ketamine-midazolam as useful sedative-analgesic options.


Effects of UV irradiation on humic acid removal by ozonation, Fenton and Fe⁰/air treatment: THMFP and biotoxicity evaluation.
Effects of UV irradiation on humic acid (HA) removal by Fe(0)/air, ozonation and Fenton oxidation were investigated. The trihalomethane forming potential (THMFP) and toxicity of treated solutions were also evaluated. The experimental conditions were ozone of 21 mg min(-1), H(2)O(2) of 8 × 10(-4)M, Fe(0) of 20 g L(-1), air flow of 5 L min(-1), and UVC of 9 W. Results indicated that Fe(0)/air rapidly removed HA color (>99%) and COD (90%) within 9 min. 51-81% of color and 43-50% of COD were removed by ozonation and Fenton oxidation after 60 min. Both UV enhanced ozone and Fenton oxidation removed HA, but the Fe(0)/air process did not. Spectrum results showed all processes effectively diminished UV-vis spectra, except for ozonation. The THMFP of Fe(0)/air-treated solution (114 μg L(-1)) was much lower than those of Fenton- (226 μg L(-1)) and ozonation-treated solutions (499 μg L(-1)). Fe(0)/air with UV irradiation obviously increased the THMFP of treated solution (502 μg L(-1)). The toxicity results obtained from Vibrio fischeri light inhibition test indicated that the toxicity of Fe(0)/air-treated solution (5%) was much lower than that of ozonation- (33%) and Fenton-treated solutions (31%). Chlorination increased the solution toxicity. The correlation between biotoxicity and chloroform in the chlorinated solution was insignificant.


New approaches for high-yield purification of Müllerian inhibiting substance improve its bioactivity.
We have established a new method to purify Müllerian inhibiting substance (MIS) with higher purity and recovery over existing procedures. Recombinant human MIS was expressed in Chinese hamster ovary cells and secreted into chemically defined serum-free media. The secreted products were concentrated by either precipitation with ammonium sulfate or lectin-affinity chromatography, each of which was followed by anion-exchange chromatography. Further separation of the active carboxy-terminal domain of MIS was achieved after cleavage by plasmin followed by lectin-affinity chromatography. This method may be applicable to other members of the transforming growth factor beta family with which MIS shares sequence homology.


The mutation of a novel Saccharomyces cerevisiae SRL4 gene rescues the lethality of rad53 and lcd1 mutations by modulating dNTP levels.
The SRL4 (YPL033C) gene was initially identified by the screening of Saccharomyces cerevisiae genes that play a role in DNA metabolism and/or genome stability using the SOS system of Escherichia coli. In this study, we found that the srl4Delta mutant cells were resistant to the chemicals that inhibit nucleotide metabolism and evidenced higher dNTP levels than were observed in the wild-type cells in the presence of hydroxyurea. The mutant cells also showed a significantly faster growth rate and higher dNTP levels at low temperature (16 degrees C) than were observed in the wild-type cells, whereas we detected no differences in the growth rate at 30 degrees C. Furthermore, srl4Delta was shown to suppress the lethality of mutations of the essential S phase checkpoint genes, RAD53 and LCD1. These results indicate that SRL4 may be involved in the regulation of dNTP production by its function as a negative regulator of ribonucleotide reductase.


Cross-country skiing injuries and biomechanics.
Cross-country skiing exercises most of the joints, muscles and tendons in the body giving the skier an all around workout. This, in combination with a low incidence of injury, makes cross-country skiing an ideal recreational and competitive sport. The new skating techniques developed during the last decade have resulted in greater velocity. The maximum speed during the diagonal stride technique is 6 m/sec compared to 8 to 9 m/sec when skating and double poling. Top-level skiers today use strong and ultra light skis of fiberglass and graphite. The ski weight is less than 500g. Today's skating technique does not require any waxing and only the cambered portion of the ski is waxed when performing the diagonal stride. The preparation of the ski course has improved with the development of special track machines. This allows top-level skiers to reach 60 to 80 km/h on downhill slopes, which has resulted in an increased risk of injury. Because cross-country skiing takes place wherever snow is available, it is difficult to establish accurate injury rates in comparison to alpine skiing which is performed on very specialised terrain at ski areas. Studies estimate the cross-country ski injury rate in Sweden to be around 0.2 to 0.5 per thousand skier days. A prospective study of cross-country ski injuries conducted in Vermont revealed an injury rate of 0.72 per thousand skier days. 75% of the injuries sustained by members of the Swedish national cross-country ski team during 1983 and 1984 were overuse injuries while 25% resulted from trauma. The most common overuse injuries included medial-tibial stress syndrome, Achilles tendon problems and lower back pain. Most common among traumatic injuries were ankle ligament sprains and fractures, muscle ruptures, and knee ligament sprains. Shoulder dislocation, acromioclavicular separation and rotator cuff tears are not infrequent in cross-country skiing. Injuries to the ulnar collateral ligament of the metacarpal phalangeal joint of the thumb (Stener's lesion) is the most common ski injury involving the upper extremity. Cross-country skiers 16 to 21 years of age complained more frequently of mild lower back pain than similarly aged non-skiers. This may result from repetitive hyperextension motions during the kick phase and the recurring spinal flexion and extension during the double poling phase. Repeated slipping on hard and icy tracks infrequently produce partial tears or microtrauma in the muscle tendinous units of the groin.(ABSTRACT TRUNCATED AT 400 WORDS)


Pediatric tracheostomy audiometric outcomes - A quality improvement initiative.
Pediatric tracheostomy patients disproportionately experience hearing loss and are at risk for delayed identification due to their medical complexity. Nonetheless, protocols to monitor hearing in these children are lacking. This quality improvement (QI) initiative aimed to increase the rates of audiometric testing within 12 months of pediatric tracheostomy placement. A retrospective cohort study included children who underwent tracheostomy under 18 months of age between 2012 and 2020. Rates of audiometric assessments before and after QI project implementation (2015) were reported along with hearing loss characteristics. A total of 253 children met inclusion. Before project initiation (2012-2014), 32% of children (28/87) obtained audiometric testing within 12 months after tracheostomy. During the first three years of implementation (2015-2017), 39% (38/97) were tested, while 55% (38/69) were tested during the subsequent three years (2018-2020) (P = .01). A passing newborn hearing screen was obtained for 70% of the 210 children with a recorded result, and 198 survived at least 12 months to receive audiometric testing at a median of 11.3 months (IQR: 6.2-22.8) after tracheostomy. Hearing loss was identified for 44% of children (N = 88), of which 42 children initially passed newborn hearing screen. A second assessment was obtained for 62% of children (123/198) at a median of 11.3 months (IQR: 4.5-17.5) after the initial test. In this group, 23% with a previously normal audiometric exam were found to have hearing loss (15/66). QI initiatives designed to monitor hearing loss in children with a tracheostomy can result in improved rates of audiometric assessments. This population has disproportionately high rates of hearing loss, including delayed onset hearing loss making audiometric protocols valuable to address speech and language development delays.


MicroRNA-101 regulates oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells.
RNA-seq technology can be used for the detection of miRNA transcripts in tissues and cells at specific periods and under specific treatment conditions, which can easily and effectively screen out differential transcripts. The purpose of this study was to compare miRNA expression in porcine cumulus cells before and after oocyte maturation, and to investigate the mechanism whereby cumulus cells may influence oocyte maturation. To that aim, cumulus cells surrounding GV- and MII-stage oocytes were isolated, and their differences in miRNA expression were examined using miRNA-seq. 143 differentially expressed miRNAs were identified, among which miR-101 was selected and further verified by qPCR. Moreover, miR-101 was found to target HAS2 through target gene prediction, luciferase-based co-transfection and cumulus cells transfection. Transfection of COCs with miR-101 mimics or inhibitor revealed that the miR-101 could inhibit oocyte IVM by regulating the expanding of CCSs, but had no effect on the embryo development competence. These findings demonstrated that miR-101 regulated oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells.


Axial compression performance of square concrete filled double skin SHS steel tubular columns confined by CFRP.
This paper focuses on the axial compression performance of 15 concrete-filled double skinned tubes CFDST columns with different CFRP reinforcement schemes. The design of this test used an outer square steel tube with a square steel tube inside, with concrete poured at the sandwich and the inner steel tube kept hollow. The structure is both cost effective and allows the hollow to be used for utility access. However, in recent years damage to CFDST has occurred due to fire, earthquakes, corrosion etc. Therefore, research into the reinforcement and repair of this structure is crucial. Compared to other reinforcement methods, FRP has the advantage of being lighter and more robust and does not significantly alter the original structure. In this study, the mechanical properties of the specimens were further analyzed from the data of load displacement, peak load and ultimate displacement by mainly observing and analyzing the damage mechanism of the specimens through the strengthening effect of different strengthening schemes for different hollow ratios. The results show that when the hollow ratio is not bigger than 0.33, the CFRP reinforcement effect is relatively obvious, especially the three-layer CFRP wrapped CFDST specimens have a substantial increase in bearing capacity and stiffness. Finally, an analytical study was carried out based on previous research and the experimental results agreed well with the calculated results.


[The effect of plasma nitriding on tungsten burs].
The authors have experimented the nitriding's effects on some cilindrical burs carbide utilized in dentistry after disamination on the applications methodics on plasma nitriding in neurosurgery, orthopedic surgery and in odontotherapy. This reacherys point out that nitriding plasma a durings increase and cutis greater capacity establish.


Progress towards achieving health for all New Zealanders by the year 2000.
New Zealand has been faced in recent years with a serious failure to maintain its relative position, in comparison to other OECD countries, in its social, economic and health status indicators. Although health costs so far have been successfully controlled, through a largely capitation funded service, its health organisational problems are typical of developed countries including major problems of equity and efficiency. Despite these problems some important recent initiatives give optimism for future health improvement. These include the spread of the service concept through service development groups and moves towards decentralisation through area health boards. Population-based funding of hospital and area health boards, supplemented with service planning guidelines, has proved to be an important lever for change. Maori health initiatives are beginning to show the way to improving the status of this disadvantaged section of society and perhaps for other New Zealanders as well. Important issues yet to be faced include establishing an effective central organisation for the health services, education and training for leadership and a more central place for the still largely fragmented and isolated primary health care services.


Predictive factors of subjective outcomes after septoplasty with and without turbinoplasty: can individual perceptual differences of the air passage be a main factor?
Although septoplasty provides adequate correction of septal deviation, patients are not always satisfied with the procedure. The degree of satisfaction after septal surgery may be affected by individual differences in the perception of one's nasal passage changes and emotional factors. The aim of this study is to identify the predictive factors that influence subjective septoplasty outcomes. Forty-nine patients with septal deviation and nasal obstruction were enrolled. Forty-three patients completed the study 3 months after surgery. Age, gender, allergies, smoking, and degree of septal deviation were evaluated. The differences in the visual analogue scale for nasal obstruction and nasal volume measured by acoustic rhinometry between pre-decongestant and post-decongestant states were analyzed. A stress questionnaire (SQ) and Beck's depression index (BDI) were also used to evaluate the emotional factors. Subjective satisfaction was evaluated as the difference in nasal obstruction symptom evaluation (NOSE) scores between baseline and 3 months postoperation. Subjective satisfaction was not related to individual perceptual differences in nasal passage changes, depression index, age, gender, allergy status, smoking, or degree of septal deviation (p > 0.05 in all; univariate analysis). The baseline SQ and NOSE scores were significant predictive factors in univariate analysis. However, on multiple regression, only the baseline NOSE scores were related to subjective satisfaction after septoplasty. Individual perceptual differences of air passage changes and emotional factors do not predict subjective symptom improvement after septoplasty. Baseline symptoms were the only predictive factor for patient satisfaction after septoplasty.


Nanomechanical and structural study of Au38 nanocluster Langmuir-Blodgett films using bimodal atomic force microscopy and X-ray reflectivity.
Langmuir-Blodgett (LB) technique allows the deposition of gold nanoparticles and nanoclusters (atomically precise nanoparticles below 2 nm in diameter) onto solid substrates with an unprecedented degree of control and high transfer ratios. Nanoclusters are expected to follow the crinkle folding mechanism, which promotes the formation of trilayers of nanoparticles but kinetically disfavors the formation of the fourth layer. LB films of Au38(SC2H4Ph)24 nanocluster were prepared at a range of surface pressures in the bilayer/trilayer regime and their internal structure was analyzed with X-ray Reflectivity (XRR) and Grazing-Incidence Wide-Angle X-ray Scattering (GIWAXS). Bimodal atomic force microscopy (AFM) imaging was used to quantify the elastic modulus, which can be correlated with the topography at the same point on the surface. Nanocluster bilayers and trilayers exhibited the elastic moduli of ca. 1.2 GPa and 0.9 GPa respectively. Films transferred in the 20-25 mN/m surface pressure regime displayed a particular propensity to form highly vertically organized trilayers. Further compression resulted in disorganization of the layers. Crucially, the use of two cantilevers of contrasting stiffness for bimodal AFM measurements has demonstrated a new approach to quantify the mechanical properties of ultrathin films without the use of deconvolution algorithms to remove the substrate contribution.


Overexpression of OsHsp 18.0 in rice enhanced tolerance to heavy metal stress.
OsHsp18.0 plays a key role in cross-protection of rice seedlings from damages to photochemical systems and cellular membranes, caused by Cd and Cu stresses.


Preferential conduction travelling from the left coronary cusp to the right ventricular outflow tract via the right coronary cusp of the aorta.
This report describes a case of premature ventricular contractions with the preferential pathway traveling from the left coronary cusp (LCC) to the right ventricular outflow tract (RVOT) via the right coronary cusp (RCC). The earliest activation was recorded within the LCC, while the successful ablation site was the RCC, where the second earliest prepotential was recorded. The remediable ablation site for ventricular arrhythmias (VAs) arising from the left ventricular (LV) ostium may not necessarily be the site of the earliest activation, but may be the site with the potential representing the preferential pathway.


Angiography-derived index of microvascular resistance in takotsubo syndrome.
Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an "adrenergic storm" upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.


Parkes Weber or Klippel-Trenaunay syndrome? Non-invasive diagnosis with MR projection angiography.
Klippel-Trenaunay and Parkes Weber (Klippel-Trenaunay-Weber) syndromes consist of vascular malformations of the capillary, venous and lymphatic systems combined with soft tissue and bone hypertrophy of the affected extremity. Klippel-Trenaunay syndrome is a pure low-flow condition, while Parkes Weber syndrome is characterized by significant arteriovenous fistulas. The distinction of both entities is relevant, since the prognosis and therapeutic strategies differ significantly. Our purpose is to demonstrate that thick-slice dynamic magnetic resonance projection angiography (MRPA) is a non-invasive tool to detect arteriovenous shunting in Parkes Weber syndrome. Four patients underwent MR imaging and MRPA. MRPA demonstrated arteriovenous shunting in three patients. Arteriovenous shunting was characterized by early appearing draining veins. The time of arrival between normal arteries and pathological veins varied between less than 0.5 and 1.0 s. Therefore, the diagnosis in these cases could be specified as Parkes Weber syndrome. In all these cases, arteriovenous shunting was confirmed by intraarterial digital subtraction angiography. One patient showed normal results in MRPA and could be diagnosed as having Klippel-Trenaunay syndrome.


Isolation and identification of the Sersenk strain of goat pox virus in Iraq.
Goat pox virus was isolated during an outbreak of pox infection among goats in the Sersenk district, Iraq. The isolated virus grew on the chorioallantoic membranes of developing chick embryos and in primary lamb testis cell cultures. It was identified morphologically as a pox virus and serologically as a member of the Capripoxvirus group in the family Poxviridae. The isolated virus was designated the "Sersenk" strain.


Counterion-induced actin ring formation.
Actin filaments form rings and loops when > 20 mM divalent cations are added to very dilute solutions of phalloidin-stabilized filamentous actin (F-actin). Some rings consist of very long single actin filaments partially overlapping at their ends, and others are formed by small numbers of filaments associated laterally. In some cases, undulations of the rings are observed with amplitudes and dynamics similar to those of the thermal motions of single actin filaments. Lariat-shaped aggregates also co-exist with rings and rodlike bundles. These polyvalent cation-induced actin rings are analogous to the toroids of DNA formed by addition of polyvalent cations, but the much larger diameter of actin rings reflects the greater bending stiffness of F-actin. Actin rings can also be formed by addition of streptavidin to crosslink sparsely biotinylated F-actin at very low concentrations. The energy of bending in a ring, calculated from the persistence length of F-actin and the ring diameter, provides an estimate for the adhesion energy mediated by the multivalent counterions, or due to the streptavidin-biotin bonds, required to keep the ring closed.


Treatment for occult breast cancer: A propensity score analysis of the National Cancer Database.
Controversy exists regarding optimal treatment of occult breast cancer (OBC). Treatment options include mastectomy alone (MAST), radiation alone (XRT), or mastectomy with radiation (MXRT). We queried the National Cancer Database from 2004 to 2014 for patients with OBC who underwent MAST, XRT, or MXRT. We utilized propensity score matching to perform three head-to-head comparisons. Kaplan-Meier analysis was performed to compare overall survival (OS). A total of 190 patients received XRT, 237 received MAST, and 244 received MXRT. In the MXRT vs. XRT comparison, 5-year OS was 78.2% and 82.8%, respectively. In the MXRT vs. MAST comparison, 5-year OS was 81.5% and 86.7%, respectively. In the MAST vs. XRT comparison, 5-year OS was 83.2% and 82.5%, respectively. There was no difference in OS for all paired comparisons. There were no OS differences in patients undergoing MAST, XRT, or MXRT, suggesting that breast conservation can be considered in patients with OBC.


The upper explosion limit of lower alkanes and alkenes in air at elevated pressures and temperatures.
The upper explosion limit (UEL) of ethane-air, propane-air, n-butane-air, ethylene-air and propylene-air mixtures is determined experimentally at initial pressures up to 30 bar and temperatures up to 250 degrees C. The experiments are performed in a closed spherical vessel with an internal diameter of 200 mm. The mixtures are ignited by fusing a coiled tungsten wire, placed at the centre of the vessel, by electric current. Flame propagation is said to have taken place if there is a pressure rise of at least 1% of the initial pressure after ignition of the mixture. In the pressure-temperature range investigated, a linear dependence of UEL on temperature and a bilinear dependence on pressure are found except in the vicinity of the auto-ignition range. A comparison of the UEL data of the lower alkanes shows that the UEL expressed as equivalence ratio (the actual fuel/air ratio divided by the stoichiometric fuel/air ratio) increases with increasing carbon number in the homologous series of alkanes.


NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy.
Neither profiles nor prognostic value of cardiac N-terminal proBNP (NT-proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo. Baseline and follow-up plasma concentrations of NT-proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol. NT-proBNP concentrations were increased at baseline (mean+/-S.D.=579+/-822 pmol/l, median=322.5 pmol/l) with a marked decrease during follow-up in the carvedilol, but not in the placebo group. One-year mortality rates were 3.9, 12 and 27.9% in the lower, middle and upper tertiles of NT-proBNP, respectively. When mortality was calculated separately in the placebo and carvedilol group, rates were 0.8, 6.3 and 19.1% in the carvedilol treated but 6.7, 17.9 and 36.9% in the placebo treated patients. NT-proBNP was a powerful predictor of subsequent all-cause mortality in patients with severe CHF. This marker should therefore be further evaluated for risk stratification and monitoring of therapy in CHF.


Visceral inputs to neurons in the anterior hypothalamus including those that project to the periaqueductal gray: a functional anatomical and electrophysiological study.
The present study was designed to examine peripheral, in particular noxious visceral, inputs to neurons in the hypothalamus that project to the midbrain periaqueductal gray. The induction of Fos protein was used to localize hypothalamic neurons that were activated by noxious visceral stimulation. This was combined with retrograde transport of fluorescent latex microspheres from identified "pressor" and "depressor" sites in the dorsolateral/lateral or ventrolateral columns of the periaqueductal gray. A second series of electrophysiological experiments examined the receptive field characteristics, including the incidence of viscerosomatic convergence, of neurons in the ventral part of the anterior hypothalamus. Noxious visceral stimulation (intraperitoneal acetic acid) induced Fos-like immunoreactivity in significantly more neurons in the hypothalamus than control stimuli (intraperitoneal saline and intravenous phenylephrine). Particularly high numbers of Fos-positive neurons were found in the paraventricular nucleus, the supraoptic nucleus and ventral regions of the anterior hypothalamus. When combined with retrograde tracing from "depressor" sites in the ventrolateral periaqueductal gray, the highest numbers of double-labelled neurons were localized in the paraventricular nucleus and the lateral area of the anterior hypothalamus. However, the regions that contained the greatest proportions of Fos-positive neurons that projected to "depressor" sites in the ventrolateral periaqueductal gray were the lateral area of the anterior hypothalamus and its rostral extension, the lateral preoptic area. Fewer double-labelled neurons were localized in the hypothalamus after retrograde transport from sites in the dorsolateral/lateral periaqueductal gray compared to the results obtained from injections of tracer in the ventrolateral periaqueductal gray. Furthermore, the numbers of Fos-positive hypothalamic neurons that projected to the dorsolateral/lateral periaqueductal gray were very similar in experimental and control animals. The electrophysiological study confirmed that a large proportion of neurons in and around the lateral area of the anterior hypothalamus can be driven by noxious visceral stimulation and demonstrated a high incidence of viscerosomatic convergence in these cells (66% of cells driven from somatic structures were also driven by electrical stimulation of the splanchnic nerve). Somatic receptive fields of these neurons were generally large, often including all four limbs and the face. The results of the functional anatomical and electrophysiological studies have identified neurons in an area of the ventral anterior hypothalamus that are a focus of nociceptive visceral input and which project to the midbrain periaqueductal gray, in particular to its ventrolateral column. These results are discussed in relation to the roles of the anterior hypothalamus and the different longitudinal columns of the periaqueductal gray in co-ordinating autonomic and sensory functions in response to visceral pain.


Comparison of clinical outcomes of three internal fixation techniques in the treatment of olecranon fracture: a retrospective clinical study.
The application of double plating in olecranon fractures is becoming increasingly widespread. There is no research comparing this technique with traditional tension band wiring (TBW) and the single plate technique. The purpose of this study was to compare the efficacy of three fixation techniques in olecranon fractures. From March 2016 to May 2020, we collected the clinical data of 95 patients with olecranon fractures who underwent surgical treatment. Thirty-five patients received TBW surgery (TBW Group), 32 patients received a 3.5 mm locking compression plate (LCP, 3.5 mm LCP Group), and 28 patients received double mini-locking plate treatment (DP Group). The operation time, fracture union time, time of return to work, range of motion (ROM), soft tissue stimulation to remove internal fixation, and patient-related functional results (the Weseley score, Mayo Elbow Performance Score [MEPS], and Disabilities of Arm, Shoulder and Hand Score [DASH]) were recorded. The clinical results and complications of the three internal fixation techniques were compared. The average follow-up time was 15.011.82 months (12-18 months). All patients' fractures healed by first intention. There were no statistically significant differences in the operation time, fracture union time, ROM, Weseley score, MEPS or DASH scores of the three groups of patients. The postoperative return time for patients in the TBW group was 10.002.15 weeks, the 3.5 mm LCP group was 9.561.93 weeks, and the DP group was 8.432.38 weeks (P = 0.014); 12 patients in the TBW group required removal of plant due to soft tissue stimulation, the 3.5 mm LCP group had 8 cases, and the DP group had 2 cases (P = 0.038). The postoperative clinical results and elbow joint function of patients with olecranon fractures fixed by tension band wiring, 3.5 mm LCP and double mini-locking plate are similar, which indicates that double-plate technology can be used as an alternative to the two groups of traditional techniques. In addition, double-plate technology also helps patients return to work earlier and has a lower incidence of soft tissue stimulation.


Effect of sonication on the quality attributes of juçara, banana and strawberry smoothie.
Effect of sonication on the quality parameters of juçara, banana and strawberry smoothie was evaluated using a rotational central composite design with power (73.5-250.0 W) and time (7-36 min) as independent variables. The sonicated smoothie was evaluated regarding anthocyanins, instrumental color and rheological and physicochemical parameters. Within the evaluated processing conditions, 86% of anthocyanins were retained. The pH and acidity of the smoothie wasn't affected by the independent variables. Regarding instrumental color parameters, only luminosity was affected by the operational conditions. The cavitation phenomenon decreased the apparent viscosity of the smoothie. The sonicated smoothie presented non-Newtonian behavior, with characteristics of a pseudoplastic fluid (n < 1) in all treatments and control. Taking into account that the highest anthocyanin retention was observed at 147 W for 2 min, this condition was the most recommended for the processing of the product.


Investigating the financial impact of porcine reproductive and respiratory syndrome on smallholder pig farmers in Cambodia.
Porcine reproductive and respiratory syndrome (PRRS) was first identified in Cambodia in 2010, causing serious problems on affected farms, although the costs of the disease have not been well defined. The household financial impact of a PRRS outbreak in Cambodia was investigated using partial budget analysis, examining the economic benefit of three proposed interventions: (i) quarterly PRRS vaccine use, (ii) biosecurity implementation, and (iii) implementation of vaccination and biosecurity. The analyses were applied to three farm models: (i) a two-sow breeder; (ii) a five-pig fattener; and (iii) a single-sow, three-pig farrow-to-finish/breeder. Data was derived from a knowledge, attitude, and practice survey of 240 smallholder farmers (61 with pigs) from 16 villages across 5 provinces, plus case studies of 12 farmers selected for more detailed financial analysis. The study indicated that financial losses associated with PRRS were severe, with a 25% mean loss to the annual household income of 61 interviewed farmers. Partial budget analysis identified a strongly positive incentive for vaccination and biosecurity to be implemented in combination, with the highest annual net benefit of USD 357.10 realised by the breeder system. However, due to current scarcity of the PRRS vaccine and its high cost to smallholders, biosecurity interventions may be more cost-effective, especially for low PRRS incidence regions. It was concluded that PRRS critically constrains the profitability of smallholder pig farms and that these findings will assist development of village-level livestock disease risk management programmes that encourage adoption of vaccination and biosecurity practices to enhance farmer livelihoods in Cambodia.


Age-related, interindividual, and right/left differences in anterior-posterior foot pressure ratio in preschool children.
This study aimed to examine age-related, interindividual, and right/left differences in anterior-posterior foot pressure ratio in 764 preschool children (364 boys and 400 girls) aged 3.5-6.5 years. Subjects maintained an upright standing posture for 10 seconds on the Footview Clinic, an instrument designed to calculate the anterior-posterior foot pressure ratio. The ratio of anterior foot pressure in each subject's right and left feet was selected as a variable, and the mean of a 10 s measurement was used for analysis. The ratio of anterior foot pressure was significantly larger in the right foot than in the left foot. With regard to age, the ratio of anterior foot pressure was significantly larger in children aged over 4.5 years than in children aged 3.5 years. It was also larger in children aged 6 and 6.5 years than in children aged 4 years. Interindividual differences in variables were large, and coefficients of variance were highest in children aged 3.5 years and lowest in children aged 6.5 years. In conclusion, anterior foot pressure increases with age in preschool children. Interindividual differences in anterior foot pressure are large and tend to decrease with age. Furthermore, the anterior foot pressure is slightly higher in the right foot than in the left foot. These results will be useful for various studies, such as examining relationships between the anterior-posterior foot pressure ratio and factors, such as untouched toes, physical fitness, and level of exercise.


Musculoskeletal ultrasound findings in paracoccidioidomycosis.
Paracoccidioidomycosis is a fungal infection endemic to South America. The infection is usually asymptomatic and mostly affects the upper and lower respiratory tracts with clinical-radiological dissociation. Joint involvement is rare with no specific pattern or radiological injury. We report a case of paracoccidioidomycosis in which the patient's initial symptoms were hoarseness and arthritis. After an ultrasound examination, we performed the differential diagnosis of other noninfectious arthropathies and analysis of the material collected, which revealed infection with the fungus Paracoccidioides brasiliensis.


Viral oncoapoptosis of human tumor cells.
Many cancer cells refractory to radiation treatment and chemotherapy proliferate because of loss of intrinsic programmed cell death (apoptosis) regulation. Consequently, the resolution of these cancers are many times outside the management capabilities of conventional therapeutics. We now report that replication-defective delta27 herpes simplex virus (rd delta27) triggers apoptosis in three representative transformed human cell lines. Susceptibility to virus-induced cell death is dependent on the abundance and distribution of modified p53 protein in the tumor cells indicating specific targeting of the treatment. Primary human and mouse fibroblast cells that produce modified p53 are resistant to rd delta27 killing but not to apoptosis induced by nonviral environmental factors. These results suggest that induction of apoptosis by nonreplicating virus is a feasible genetic therapy approach for killing human cancer cells. Our findings may have important implications in designing novel virus-based anticancer strategies in appropriate animal model systems.


A brain atlas for the camouflaging dwarf cuttlefish, Sepia bandensis.
The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied marine mollusks that exhibit an array of interesting biological phenomena, including dynamic camouflage, complex social behaviors, prehensile regenerating arms, and large brains capable of learning, memory, and problem-solving.1,2,3,4,5,6,7,8,9,10 The dwarf cuttlefish, Sepia bandensis, is a promising model cephalopod species due to its small size, substantial egg production, short generation time, and dynamic social and camouflage behaviors.11 Cuttlefish dynamically camouflage to their surroundings by changing the color, pattern, and texture of their skin. Camouflage is optically driven and is achieved by expanding and contracting hundreds of thousands of pigment-filled saccules (chromatophores) in the skin, which are controlled by motor neurons emanating from the brain. We generated a dwarf cuttlefish brain atlas using magnetic resonance imaging (MRI), deep learning, and histology, and we built an interactive web tool (https://www.cuttlebase.org/) to host the data. Guided by observations in other cephalopods,12,13,14,15,16,17,18,19,20 we identified 32 brain lobes, including two large optic lobes (75% the total volume of the brain), chromatophore lobes whose motor neurons directly innervate the chromatophores of the color-changing skin, and a vertical lobe that has been implicated in learning and memory. The brain largely conforms to the anatomy observed in other Sepia species and provides a valuable tool for exploring the neural basis of behavior in the experimentally facile dwarf cuttlefish.


[Effect of acetazolamide on arterial blood lactate levels during recuperation in air from three days of hypercapnia].
After a three day-period of hypercapnia, carbonic anhydrase blockade by acetazolamide inhibits the development of arterial blood alcalosis during the return in normal environment, and thus eliminates the transient increase in lactacidemia due to glycolysis stimulation.


The impact of intravascular ultrasound guidance during drug eluting stent implantation on angiographic outcomes.
Major limitation for the use of stent in the treatment of coronary artery disease is development of stent restenosis. The impact of intravascular ultrasound (IVUS) guidance during drug eluting stent (DES) implantation is presently not yet well established. For the present study, we included 30 patients who received DES with IVUS-guided stenting (Group A) and 30 patients receiving the DES without IVUS-guided stenting (Group B). The patients were evaluated for their ninth month control angiographies and were followed during two years for the development of relevant clinical events after the DES implantations. The angiographic and clinical results were compared between the groups. After the percutaneous intervention, the minimal luminal diameter and net acute gain were significantly increased in Group A in respect to Group B (3.3 ± 0.34 vs. 2.8 ± 0.33, p < 0.01). Moreover, the rate for performing post-dilatation following stent implantation was higher in Group A than in Group B (p = 0.01). By contrast, stent restenosis rates were similar between the groups (p > 0.3). The present results indicate that the use of IVUS for the implantation of DES can increase the success rate of the intervention. The IVUS guidance during DES implantation can be complementary percutaneous intervention, in particularly by detecting the situations that need for post-dilatation.


Compensation for labyrinthine defects examined by use of a tilting room.
Visual compensation for vestibular deficiency was demonstrated by stabilometry inside a laterally tilting room. Labyrinthless patients showed a predominance of vision over the somatosensory system for a rather long time: in contrast to the controls, the labyrinthless subjects experienced the tilting room often as stationary and the stationary stabilometer as tilting, which resulted in vertical postural instability.


A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro.
Indole-3-carbinol (I3C), a naturally occurring phytochemical found in cruciferous vegetables, has received much attention due to its translational potential in cancer prevention and therapy. In this study, we investigated the antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095. The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis. Moreover, the observed down regulation of IKKα and IKKβ expression by OSU-A9 is not reported for I3C. OSU-A9 also induces both the production of reactive oxygen species and the endoplasmic reticulum stress. Taken together, these results suggest the translational value of OSU-A9 in oral squamous cell cancer therapy in the future.


Pressor effects from daily events and laboratory complex stimuli relating personality factors.
Our preliminary research has attempted to establish a series of methods to study the complex interactions occurring between pressor reactivity and personality profile. Ten untreated mild hypertensives (age 42.9 +/- 8) without damaged target organs were recruited from an outpatient hypertension center along with an equal number of normotensive volunteers (age 38.2 +/- 8.1). We performed a sequence of stressor types under laboratory conditions (sensory perceptual activities, psychomotor responses, and cognitive behavior) following an order ranging from inferior levels to superior levels of systemic integration. The subjects also underwent a 24-h automatic noninvasive blood pressure recording which took into account the situational reactivity. They filled in MMPI and STAI questionnaires before and after the stressor batteries. Only the sensory-perceptual test (Stroop color test modified), the arithmetic test, and the psychomotor test provoked a significant increase in blood pressure and, in the latter test, also a significant increase of the heart rate. The test batteries' mean differences were not significant between the two groups. Similarly, the answers to the trait-anxiety questionnaires did not allow us to make a substantial division between normotensive and hypertensive subjects. On the contrary, the situational anxiety questionnaires showed a significant difference in the score reading preceding and following a task performed by the hypertensive subjects. We observed significant differences for both systolic and diastolic 24-h blood pressure data in transition from a working situation to the sleeping period. However, there was not a significant difference in hypertensive blood pressure readings recorded during work and at home.(ABSTRACT TRUNCATED AT 250 WORDS)


Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen-activated protein kinase pathway.
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.


Occurrence of chronic endometritis in different types of human adenomyosis.
Human adenomyosis has an adverse effect on female fertility. Exact mechanistic basis is still unclear. We investigated the occurrence of chronic endometritis (CE) in different types of human adenomyosis. This is a prospective non-randomized observational study enrolling patients with focal (n = 30), diffuse (n = 26), intrinsic (n = 23), and extrinsic (n = 10) adenomyosis. Endometrial biopsy samples were collected from hysterectomy specimens. Immunohistochemical analysis was performed using antibody against CD68 (Mφ marker) with biopsy samples of intrinsic/extrinsic adenomyosis and CD138 (Syndecan-1), a marker of plasma cells, in all biopsy samples. In GnRHa-untreated groups, a higher trend in the occurrence of CE, as characterized by infiltration of ≥1 plasma cells in endometrial stroma, was found in women with focal (58.8%, p = 0.0849) and diffuse adenomyosis (60.0%, p = 0.0841) comparing to control women (10.0%). In women with focal adenomyosis, ipsilateral side showed a significantly higher occurrence of CE (58.8%) than on the contralateral side (11.7%) (p = 0.043). Tissue infiltration of macrophages in endometria was significantly higher in intrinsic than in extrinsic adenomyosis (p = 0.03) without showing any significant difference in the occurrence of CE between these two variants of adenomyosis. A variable occurrence of CE in different types of adenomyosis may be involved in adverse reproductive outcome.