Cardiac and hemodynamic effects of the selective bradycardic agent KC 8857 during exercise-induced myocardial ischemia.
The effects of an in vitro bradycardic agent without negative inotropism, KC 8857 (3,7-di-(cyclopropylmethyl)-9,9-tetramethylene-3,7-diazabicyclo-[3.3.1]- nonane dihydrochloride), were tested in chronically instrumented dogs in a model of exercise-induced myocardial ischemia. KC 8857 was i.v. infused during critical stenosis of the circumflex branch of the left coronary artery which led to exercise-induced myocardial dysfunction. KC 8857 caused a decrease in heart rate, left ventricular dp/dtmax and calculated myocardial oxygen demand at rest and during exercise. Since positive dp/dtmax values at a given heart rate were not altered by KC 8857 it may be assumed that myocardial function was restored mainly by the decrease in heart rate.


Anatomical variants of the celiac artery in the sheep, with special reference to the celiomesenteric arterial trunk.
The course of celiac artery is described on the basis of studies on the carcases of 28 three-year old merino sheep of both sexes (7 males and 21 females). These investigations have shown that there are two main variants of the celiac artery. Of these, 60.7 percent of the sheep dissected exhibited the first, characterized by a separate issue of the celiac artery from the aorta. The second variant, characterized by the issue of the celiac artery from a celiomesenteric arterial trunk common to the celiac and superior mesenteric arteries, was found in 39.3 percent of the specimens. In the material studies, besides the variability in the course of the celiac artery, individual differences were found in the structure and topography of the neurovegetative vascular plexuses.


In vivo mutations at the H-2 locus in mouse lymphocytes.
An experimental system has been developed to study in vivo autosomal mutations in murine splenic lymphocytes. Mutant lymphocytes were isolated by immunocytotoxicity using monoclonal antibodies directed against the k and d alleles of the K and D H-2 histocompatibility loci and were enumerated using limiting-dilution cloning. Genomic allele loss in mutant clones was detected using allele-specific primers in a polymerase chain reaction. Mutant clones were classified on the basis of phenotypic and genotypic criteria into "no change", deletion or recombination mutants. The geometric mean mutation frequency in 102 mice was 2.42 x 10(-4). Detailed phenotypic and genotypic study of 87 mutant clones from 4 mice revealed "no change" mutants in 83%, mutants due to deletion in 7% and mutants due to recombination in 7%. Anomalous results were obtained in 3% of mutant clones. The development of an animal model for study of in vivo mutations at an autosomal locus will further advance study of mutations, particularly those involving chromosomal changes such as mitotic recombination.


Asymmetric nitroallylation of arylboronic acids with nitroallyl acetates catalyzed by chiral rhodium complexes and its application in a concise total synthesis of optically pure (+)-gamma-lycorane.
[reaction: see text]A new rhodium-catalyzed highly enantioselective nitroallylation of 2-nitrocyclohex-2-enol esters with arylboronic acids is described. A rhodium complex of [RhOH(COD)]2 and optically pure BINAP is the optimal catalyst that provides good yields and high enantioselectivities ranging from 90 to 99% ee for various arylboronic acids at 50 degrees C. A concise total synthesis of optically pure (+)-gamma-lycorane in overall 38% yield was achieved on the basis of this new method.


Understanding the Relationship Between Antiviral Prescription Data and COVID-19 Incidence in New York City: A Retrospective Cohort Study.
The coronavirus disease 2019 (COVID-19) pandemic has caused more than 675 million confirmed cases and nearly 7 million deaths worldwide [1]. While testing for COVID-19 was initially centered in health care facilities, with required reporting to health departments, it is increasingly being performed in the home with rapid antigen testing [2]. Most at-home tests are self-interpreted and not reported to a provider or health department, which could lead to delayed reporting or underreporting of cases [3]. As such, there is a strong possibility that reported cases may become a less reliable indicator of transmission over time.


Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy. An outcome study.
The functional outcome of patients with lumbar herniated nucleus pulposus without significant stenosis was analyzed in a retrospective cohort study. Inclusion criteria were as follows: 1) a chief complaint of leg pain, primarily; 2) a positive straight leg raising (SLR) at less than 60 degrees reproducing the leg pain; 3) a computed tomography (CT) scan demonstrating a herniated nucleus pulposus without significant stenosis by a radiologist's reading, which was also confirmed by the authors; 4) a positive electromyogram (EMG) demonstrating evidence of radiculopathy; and 5) response to a follow-up questionnaire. All patients had undergone an aggressive physical rehabilitation program consisting of back school and stabilization exercise training. Of a total of 347 consecutively identified patients, 64 patients with an average follow-up time of 31.1 months met the inclusion criteria and constituted the study population. They were sent questionnaires that inquired about activity level, pain level, work status, and further medical care. The patients with neurologic loss, extruded discs, and those seeking a second opinion regarding surgery were identified and subgrouped. Results for the total group included 90% good or excellent outcome with a 92% return to work rate. For the subgroups with extruded discs and second opinions, 87% and 83% had good or excellent outcomes, respectively, all (100%) of whom returned to work. Sick leave time for these subgroups was 2.9 months (+/- 1.4 months) and 3.4 months (+/- 1.7 months), respectively. These results compared favorably with previously published surgical studies. Four of six patients who required surgery were found to have stenosis at operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the diagnostic value of virtual touch tissue quantification and virtual touch tissue imaging quantification in infants with biliary atresia.
This study aimed to compare the diagnostic performance of vital touch tissue quantification (VTQ) and virtual touch tissue imaging quantification (VTIQ) in diagnosing infants with biliary atresia (BA) from jaundiced infants. In this study, 26 jaundiced infants with BA, 33 jaundiced infants without BA, and 40 normal infants were enrolled. The hepatic shear wave velocity (SWV) of each infant was determined by VTQ and VTIQ examinations, respectively. Then, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) and optimal cut-off values were calculated to evaluate the sensitivities and specificities of VTIQ and VTQ for BA. The mean values of SWV of the control group measured by VTQ and VTIQ were (1.09 ± 0.18) m/s and (1.36 ± 0.21) m/s, respectively. The mean values of SWV of the non-BA group measured by VTQ and VTIQ were (1.30 ± 0.28) m/s and (1.52 ± 0.29) m/s, respectively. The mean values of SWV of the BA group measured by VTQ and VTIQ were (2.36 ± 0.36) m/s and (2.43 ± 0.29) m/s, respectively. The diagnostic threshold of VTQ and VTIQ to diagnose BA was 1.77 and 1.92 m/s. The sensitivities of VTQ and VTIQ to diagnose BA were 90.9% and 95.5%. The specificities of VTQ and VTIQ to diagnose BA were 68.4% and 78.9%. Vital touch tissue quantification and VTIQ could help distinguish infants with BA from jaundiced infants by measuring the liver SWV values. VTIQ has higher sensitivity and specificity than VTQ.


Integrated spatially resolved metabolomics and network toxicology to investigate the hepatotoxicity mechanisms of component D of Polygonum multiflorum Thunb.
The liver toxicity of Reynoutria multiflora (Thunb.) Moldenke. (Polygonaceae) (Polygonum multiflorum Thunb, PM) has always attracted much attention, but the related toxicity materials and mechanisms have not been elucidated due to multi-component and multi-target characteristics. In previous hepatotoxicity screening, different components of PM were first evaluated and the hepatotoxicity of component D [95% ethanol (EtOH) elution] in a 70% EtOH extract of PM (PM-D) showed the highest hepatotoxicity. Furthermore, the main components of PM-D were identified and their hepatotoxicity was evaluated based on a zebrafish embryo model. However, the hepatotoxicity mechanism of PM-D is unknown. This work is to explore the hepatotoxicity mechanisms of PM-D by integrating network toxicology and spatially resolved metabolomics strategy. A hepatotoxicity interaction network of PM-D was constructed based on toxicity target prediction for eight key toxic ingredients and a hepatotoxicity target collection. Then the key signaling pathways were enriched, and molecular docking verification was implemented to evaluate the ability of toxic ingredients to bind to the core targets. The pathological changes of liver tissues and serum biochemical assays of mice were used to evaluate the liver injury effect of mice with oral administration of PM-D. Furthermore, spatially resolved metabolomics was used to visualize significant differences in metabolic profiles in mice after drug administration, to screen hepatotoxicity-related biomarkers and analyze metabolic pathways. The contents of four key toxic compounds in PM-D were detected. Network toxicology identified 30 potential targets of liver toxicity of PM-D. GO and KEGG enrichment analyses indicated that the hepatotoxicity of PM-D involved multiple biological activities, including cellular response to endogenous stimulus, organonitrogen compound metabolic process, regulation of the apoptotic process, regulation of kinase, regulation of reactive oxygen species metabolic process and signaling pathways including PI3K-Akt, AMPK, MAPK, mTOR, Ras and HIF-1. The molecular docking confirmed the high binding activity of 8 key toxic ingredients with 10 core targets, including mTOR, PIK3CA, AKT1, and EGFR. The high distribution of metabolites of PM-D in the liver of administrated mice was recognized by mass spectrometry imaging. Spatially resolved metabolomics results revealed significant changes in metabolic profiles after PM-D administration, and metabolites such as taurine, taurocholic acid, adenosine, and acyl-carnitines were associated with PM-D-induced liver injury. Enrichment analyses of metabolic pathways revealed tht linolenic acid and linoleic acid metabolism, carnitine synthesis, oxidation of branched-chain fatty acids, and six other metabolic pathways were significantly changed. Comprehensive analysis revealed that the hepatotoxicity caused by PM-D was closely related to cholestasis, mitochondrial damage, oxidative stress and energy metabolism, and lipid metabolism disorders. In this study, the hepatotoxicity mechanisms of PM-D were comprehensively identified through an integrated spatially resolved metabolomics and network toxicology strategy, providing a theoretical foundation for the toxicity mechanisms of PM and its safe clinical application.


Stability evaluation of ZnO nanosheet based source-gated transistors.
Semiconducting nanostructures are one of the potential candidates to accomplish low-temperature and solution-based device assembly processes for the fabrication of transistors that offer practical solutions toward realizing low-cost flexible electronics. Meanwhile, it has been shown that by introducing a contact barrier, in a specific transistor configuration, stable device operation can be achieved at much reduced power consumption. In this work, we investigate both one-dimensional ZnO nanowires (NWs) and two-dimensional nanosheets (NSs) for high performance and stable nano-transistors on conventional Si/SiO2 substrates. We have fabricated two variant of transistors based on nanoscale single-crystalline oxide materials: field-effect transistors (FETs) and source-gated transistors (SGTs). Stability tests are performed on both devices with respect to gate bias stress at three different regimes of transistor operation, namely off-state, on-state and sub-threshold state. While in the off-state, FETs shows comparatively better stability than SGTs devices, in both sub-threshold and on-state regimes of transistors, SGTs clearly exhibits better robustness against bias stress variability. The present investigation experimentally demonstrates the potential advantages of SGTs over FETs as driver transistor for AMOLEDs display circuits which require very high stability in OLED driving current.


Delayed excision of a defect after free omental transfer with uncertain viability; a case report.
We present the case of a 45-year-old man with an extensive radionecrotic ulcer of the anterior aspect of the thigh and exposure of the femur. Difficulty in the revascularisation of a free omental transfer due to radiation damage to the recipient vessels led us to delay excision of the defect and to store the flap temporarily in a plastic bag close to the recipient site; 48 hours later its satisfactory appearance allowed excision of the defect and successful final inset of the omentum. Advantages of this procedure are discussed.


TIToK: A solution for bi-imbalanced unsupervised domain adaptation.
Unsupervised domain adaptation (UDA) aims to transfer knowledge via domain alignment, and typically assumes balanced data distribution. When deployed in real tasks, however, (i) each domain usually suffers from class imbalance, and (ii) different domains may have different class imbalance ratios. In such bi-imbalanced cases with both within-domain and across-domain imbalance, source knowledge transfer may degenerate the target performance. Some recent efforts have adopted source re-weighting to this issue, in order to align label distributions across domains. However, since target label distribution is unknown, the alignment might be incorrect or even risky. In this paper, we propose an alternative solution named TIToK for bi-imbalanced UDA, by directly Transferring Imbalance-Tolerant Knowledge across domains. In TIToK, a class contrastive loss is presented for classification, in order to alleviate the sensitivity to imbalance in knowledge transfer. Meanwhile, knowledge of class correlation is transferred as a supplementary, which is commonly invariant to imbalance. Finally, discriminative feature alignment is developed for a more robust classifier boundary. Experiments over benchmark datasets show that TIToK achieves competitive performance with the state-of-the-arts, and its performance is less sensitive to imbalance.


Chloroperoxidase-catalysed oxidation of 4-chloroaniline to 4-chloronitrosobenze.
The incubation of 4-chloroaniline with chloroperoxidase and H2O2 resulted in a rapid formation of 4-chloronitrosobenzene. This enzymic oxidation displayed a pH optimum at 4.4 with a Km of 8.1x10(-4)M and catalytic-centre activity of 312. The initial rate of the reaction was strongly affected by the presence of halide ions. 4-Chlorophenylhydroxylamine was even more rapidly converted into the nitroso compound. A reaction mechanism is proposed on the basis of currently accepted theory for the catalytic action of chloroperoxidae. A noteworthy aspect of this new reaction is the difference in the products previously reported for the action of classical peroxidases on anilines and the single nitroso product resulting from chloroperoxidase oxidation.


Hepatitis C virus modulates lipid regulatory factor Angiopoietin-like 3 gene expression by repressing HNF-1α activity.
HCV relies on host lipid metabolism to complete its life cycle and HCV core is crucial to this interaction. Liver secreted ANGPTL-3 is an LXR- and HNF-1α-regulated protein, which plays a key role in lipid metabolism by increasing plasma lipids via inhibition of lipase enzymes. Here we aimed to investigate the modulation of ANGPTL-3 by HCV core and identify the molecular mechanisms involved. qRT-PCR and ELISA were used to assess ANGPTL-3 mRNA and protein levels in HCV patients, the JFH-1 infectious system and liver cell lines. Transfections, chromatin immunoprecipitation and immunofluorescence delineated parts of the molecular mechanisms implicated in the core-mediated regulation of ANGPTL-3 gene expression. ANGPTL-3 gene expression was decreased in HCV-infected patients and the JFH-1 infectious system. mRNA and promoter activity levels were down-regulated by core. The response was lost when an HNF-1α element in ANGPTL-3 promoter was mutated, while loss of HNF-1α DNA binding to this site was recorded in the presence of HCV core. HNF-1α mRNA and protein levels were not altered by core. However, trafficking between nucleus and cytoplasm was observed and then blocked by an inhibitor of the HNF-1α-specific kinase Mirk/Dyrk1B. Transactivation of LXR/RXR signalling could not restore core-mediated down-regulation of ANGPTL-3 promoter activity. ANGPTL-3 is negatively regulated by HCV in vivo and in vitro. HCV core represses ANGPTL-3 expression through loss of HNF-1α binding activity and blockage of LXR/RXR transactivation. The putative ensuing increase in serum lipid clearance and uptake by the liver may sustain HCV virus replication and persistence.


Paraneoplastic syndrome of arthropathies as presenting sign for non-small cell lung cancer.
The aim of this study is to showcase an example of paraneoplastic syndrome, so other healthcare providers can be aware of early NSCLC manifestations. This is also important so providers do not dismiss review of symptoms that may not seem pertinent.


Acyclovir in human breast milk.
Acyclovir concentration was measured by radioimmunoassay in the serum and milk of a lactating woman who was treated with oral acyclovir for herpes zoster. Daily serum and milk samples showing milk concentrations that averaged being 3.24-fold higher than serum levels suggest a low infant dose. The elimination phase demonstrated a half-life of 2.8 hours in milk.


A rare long-term undetected pheochromocytoma leading to Takotsubo syndrome in an older male patient: a case report.
Takotsubo syndrome is an uncommon, acute, and reversible cardiomyopathy that occurs primarily in postmenopausal females. The clinical presentation of the syndrome resembles acute coronary syndrome, but coronary angiography reveals no obstructive coronary artery disease. Rarely, a catecholamine surge due to pheochromocytoma may induce Takotsubo syndrome. The clinical features of pheochromocytoma include paroxysmal hypertension, headache, palpitations, and profuse sweating. However, owing to the episodic, rather than continued, symptoms and signs of pheochromocytoma, its timely diagnosis poses a challenge for clinicians. Here, we report a rare case of long-term undetected pheochromocytoma leading to Takotsubo syndrome in an older male patient. A 70-year-old man presented with paroxysmal chest distress and chest pain. Examinations revealed acute coronary syndrome with normal coronary arteries, heart failure, reversible left ventricular regional wall motion abnormalities, labile blood pressure, a giant left adrenal mass, and extremely high levels of metanephrine and normetanephrine. Clinical manifestations, laboratory reports, and imaging findings suggested a diagnosis of Takotsubo syndrome caused by pheochromocytoma. Supportive therapy, administration of alpha- adrenergic receptor blockers, and left adrenal mass resection resolved the patient's symptoms. A histological examination confirmed the presence of pheochromocytoma. We reviewed his history of midbrain hemorrhage 6 years prior and found a mass in the left adrenal region by reviewing the computed tomography images of the lung that were also taken 6 years prior, on which the pheochromocytoma was evident. Our case illustrates the importance of understanding the link between pheochromocytoma and Takotsubo syndrome. A diagnosis of pheochromocytoma-induced Takotsubo syndrome should be considered during the differential diagnosis of acute coronary syndrome, especially in patients with labile blood pressure and normal coronary angiography findings; meanwhile, assessments of catecholamines and its metabolites and abdominal computed tomography scan should be performed at the right time. Clinicians should also be alert to potential pheochromocytoma in patients with unexplained cerebral hemorrhage, even in the absence of symptoms of catecholamine excess.


Attachment of adeno-associated virus type 3H to fibroblast growth factor receptor 1.
Heparan sulfate proteoglycan is thought to act as primary receptor for adeno-associated virus type 2 (AAV-2). Reported coreceptors include alphaVbeta5 integrin, fibroblast growth factor receptor 1 (FGFR-1), and hepatocyte growth factor (c-Met). The interaction of AAV type 3 (AAV-3) with possible cell membrane receptors is incompletely defined. In this study, using assays detecting competition with viral infection, virus binding inhibition assays and dot blotting, we show attachment of AAV-3 strain H to heparin, heparan sulfate, and FGFR-1. These findings provide new information on the possible receptor array used by AAV-3.


A new multifunctional hydroxytyrosol-fenofibrate with antidiabetic, antihyperlipidemic, antioxidant and antiinflammatory action.
Dyslipidemia, oxidative stress and inflammation are major risky factors involved in the pathophysiology of type 2 diabetes mellitus and atherosclerosis. Multifunctional intervene is more meaningful. The aim of this study was to evaluate the multifunctional effects of two new compounds, combination of fenofibric acid (FA) with tyrosol (T) or hydroxytyrosol (HT). Compared with fenofibrate (FF), FF-HT exhibited excellent antioxidant capacities in vitro and much improved hypolipidemia, reducing plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 76%, 54%, and 28%, while FF-T decreased the plasma parameters by 16%, 10%, and 20% in hyperlipidemic mice induced by Triton WR 1339. Furthermore, compound FF-HT exhibited significant antihyperglycemic, antihyperlipidemic, antioxidant and anti-inflammatory activities as well as attenuating hepatotoxicity in a type 2 diabetes experimental mouse model. The histological findings showed that FF-HT suppressed the development of hepatic lipid accumulation and ameliorated the damage in hepatic and pancreatic tissues compared to model mice. This study indicates for the first time that reasonable optimized drug design produce a compound entity which is conducive to the prevention of type 2 diabetes mellitus and its complications.


Pulmonary and central nervous system nocardiosis: Alcoholism as an immunocompromising factor
Nocardiosis is a disease with worldwide distribution. It is usually found in tropical areas and mainly affects immunocompromised patients, however, there are also cases where its infection has been reported in immunocompetent patients. This pathology is caused by bacteria known as Nocardia spp., which are gram-positive microorganisms and environmental saprophytes, and although exposure to Nocardia spp. is almost universal, only a small fraction of exposed people develops the disease. We present the case of a 47-year-old man, with no evidence of immunosuppression, from a rural area of Boyacá, who was admitted due to intense and intermittent headache accompanied by paresthesia and, finally, a decrease in consciousness. A brain magnetic resonance was performed and evidenced a fronto-temporo- occipital space-occupying lesion in the cortico-subcortical region with a compressive effect and displacement of the ventricular system cavities. It was suspected at first a neoplastic lesion or a brain abscess. The lesion was surgically resected, and its culture showed Nocardia africana/nova. In later studies a possible primary pulmonary focus was evidenced. Alcoholism was the only risk factor documented. The patient completed 6 weeks of hospital antibiotic treatment with favorable clinical and radiological evolution and was discharged with a 1-year plan of outpatient antibiotic therapy. Although Nocardia spp. mainly affects immunocompromised patients, evidence shows that this microorganism can also be a threat to individuals without traditional immunosuppression risk factors.


Risk factors of surgical evacuation following second-trimester medical termination of pregnancy.
Second-trimester medical termination of pregnancy (TOP) is associated with a higher risk of surgical evacuation than earlier medical TOP. Little is known about risk factors of surgical evacuation. Therefore, we assessed these risk factors among women undergoing second-trimester medical TOP. Data on 227 women were derived from a prospective randomized trial comparing 1- and 2-day mifepristone-misoprostol intervals in second-trimester medical TOP between 2008 and 2010. The rate of surgical evacuation was 30.8%. The risk of surgical evacuation was increased by a history of curettage [odds ratio (OR) 4.4; 95% confidence interval (CI) 1.7-11.7], fetal indications for TOP (OR 6.1; 95% CI 1.1-34.4), age above 24 years (OR 2.4; 95% CI 1.1-5.3) and a 2-day interval (OR 2.2; 95% CI 1.1-4.1). History of curettage, fetal indication, increasing age and 2-day interval between mifepristone and misoprostol increase the risk of surgical evacuation in cases of second-trimester medical TOP. These findings are important when optimizing clinical service in second-trimester TOP.


Study of the representativity of uranium and thorium assays in soil and sediment samples by alpha spectrometry.
The activity concentrations of soil and sediment samples are determined by alpha spectrometry with a sample size usually < 1 g. Hence, a systematic and careful procedure must be followed in the sampling and pre-treatment of the sample in order to ensure that the aliquot analysed represents the activity concentration of the entire sample. Statistical analyses of the activity concentrations of uranium and thorium isotopes in soil and sediment samples were performed to study the activity variation due to the lack of the representativity of the sample. These studies showed that, although some uncertainty in the determination of the sample activity concentration may be due to the lack of representativity (about 10%), the procedure followed for the pre-treatment of the sample can be considered adequate, providing an acceptable level of representativity.


Determining variables for repeat prostate biopsy.
During the evaluation of prostate cancer, men who have undergone transrectal ultrasound-guided biopsy with negative results present a dilemma as to what further follow-up is required. Multiple variables have been proposed throughout the literature to improve cancer detection rates not only in initial biopsy results, but also on repeat evaluation. These variables include prostate-specific antigen (PSA) velocity, PSA density, free-percent PSA, and histological findings, each of which may singly or collectively dictate the need for further biopsy. After performing a Medline literature search using specific Medical Subject Headings (prostate biopsy, repeat prostate biopsy, PSA velocity, PSA density, free-percent PSA, prostate inflammation), we critically evaluated pertinent articles. Using this accumulated data and information, we composed an algorithm to assist in the decision process for repeat biopsy.


Characteristics of periodontal mechanosensitive neurons in the first somatosensory cortex of the cat.
Response properties of periodontal mechanosensitive (PM) units which were activated by the mechanical stimulation of canine teeth were studied in the oral area of somatosensory cortex S I (anterior coronal gyrus) of the cat. Spike discharges of PM units were recorded as post-stimulus time histograms (PSTHs). Most PM units showed more or less spontaneous activity and phasic response properties to the trapezoid waveform stimulation. When the rate of stimulus application was increased, the initial peak value of the PSTH increased and its crest time decreased. Direction-selective PM units which changed their response discharge rates according to the direction of the stimuli applied to the canine teeth were found in this cortical area. Posterior-directed mechanical stimulation was more effective for eliciting the spike discharges of PM units than anterior-directed stimulation. Applying the test and conditioning stimuli to the contralateral or ipsilateral canine teeth, interactions of afferent inputs received by the mechanoreceptors of the periodontal tissues of different teeth were studied. Test responses of PM units were inhibited for 20-50 ms after the onset of the conditioning stimuli.


Synthesis and antitumor activity of spergualin analogues. II. Chemical modification of the spermidine moiety.
Chemical modifications of the spermidine moiety of an antitumor antibiotic, spergualin (Ia), and the structure-activity relationship are described. Replacement of spermidine with other polyamines decreased the antitumor activity against mouse leukemia L1210. Analogues containing an oxidized spermidine moiety that probably formed during oxidation with amine oxidase were inactive. Spermidine is indispensable for the antitumor activity. A facile method for the synthesis of glyoxyloyl polyamine, a key intermediate of spergualin-related compounds, is also reported.


Twenty year experience in maxillocraniofacial surgery. An evaluation of early surgery on growth, function and body image.
We have analyzed 404 patients with a wide variety of maxillary and craniofacial deformities. These do not include head and neck cancer patients as generally defined. Satisfaction has been high as judged by the patients, surgeons and psychiatrists. The complication rate has been significant, approximately 30%, the most common being infection or loss of bone grafts. As experience accumulated, the concept of earlier operative intervention has emerged as an aid in unlocking growth potential, diminishing secondary deformity and improving the development of body image.


A flow cytometric protocol for enumeration of endothelial progenitor cells and monocyte subsets in human blood.
Accumulating evidence intensively advises circulating endothelial progenitor cells (EPCs) and monocyte subsets as surrogate cellular biomarkers in cardiovascular and cancer disease. However, a general standard on their quantification is still elusive, thus precluding a routine monitoring and comparative interpretation of clinical studies. We intend to develop an advanced and express flow cytometric protocol for proper ex vivo quantification of monocyte subsets and EPCs in human blood. We employ now lyse/no-wash procedure and bead-based determination of absolute cell counts. We use three-color antibody panels at appropriate compensation. Analysis of rare events and low antigen expression in the EPC experiment is strengthening by sequential gating with exclusion of dead cells, as well as by matching high-intensity fluorochromes to low-density markers and by implementing the fluorescence-minus-one control. Analysis of peripheral blood of ten healthy donors revealed median (IQR) value of 1.88 (1.35-2.85) viable CD45(dim)CD34)VEGFR2+ EPCs per microliter. Analysis of monocytes revealed 329.5 (264.5-374.8), 16.0 (8.0-22.2) and 26.5 (19.8-36.3) cells per microliter for classical CD14++(high))CD16⁻, intermediate CD14++CD16+(mid) and non-classical CD14+(low))CD16++ monocytes. Our current protocol provides quantitative information under a simple gating logic while using commonly accepted fluorochromes. This assay is therefore highly adapted for routine use.


Bovine besnoitiosis: epidemiological and clinical aspects.
Bovine besnoitiosis, due to the cyst-forming apicomplexan Besnoitia besnoiti, is widespread in Africa, in Asia and in the south of Europe. This infection leads to major economic losses in cattle production with a decrease in milk production, transient of definitive sterility of bulls and mortality. Since its emergence in Europe (Germany, Spain and Centre of France), more attention has been given to this infection during the last 10 years, including the recent development of serological methods for diagnosis. The life cycle of B. besnoiti remains a mystery: the definitive host is unknown and the transmission routes are poorly understood. B. besnoiti is thought to be transmitted mainly by hematophagous insects. This paper presents a review of what is currently known of the epidemiology of bovine besnoitiosis and the key manifestations of the disease. It highlights the urgent need for research programs to improve efficient and sustainable control methods.


Assessment of COVID-19 incidence and hospitalization rate of male patients with prostatic hyperplasia depending on the intake of 5-alpha-reductase inhibitors (5-ARI). In our study, electronic medical records of 1678 patients with prostatic hyperplasia were analyzed. 1490 men aged 71 (64-76) years were selected for final analysis. Vaccination against COVID-19 was carried out in 730 patients (49%). Treatment with 5-ARI inhibitors was carried out in 269 (18.1%) patients. Among 1490 included patients 790 (53%) had COVID- 19 while 360 (45.7%) of them required hospitalization. During the multivariate analysis, only two factors were associated with the risk of COVID-19 in the cohort studied: vaccination (odds ratio (OR) =0.095; 95% confidence interval (CI) 0.074-0.122), i.e. a 90.5% chance reduction, p<0.001) and the fact of taking 5-ARI (OR=0.235; 95%CI=0.165-0.335; p<0.001), i.e. a 76.5% chance reduction. The duration of 5-ARI therapy was not associated with the incidence of new coronavirus infection. The severe course of COVID-19 which required hospitalization was positively associated with age (p=0.025) and the presence of coronary artery disease (p=0.004); and negatively associated with the frequency of vaccination (p<0.001) and treatment of 5-ARI (3.1% vs. 11.6%, p<0.001). In a multivariate analysis of outpatient patients with prostatic hyperplasia who had COVID-19, 5-ARI intake (OR=0.240; 95% CI 0.122-0.473; p<0.001) and vaccination (OR = 0.570; 95% CI 0.401-0.808; p=0.002). The factors associated with increased chances of hospitalization due to the severe course of COVID-19 were coronary heart disease (+43.8%, p=0.019) and older age (+1.7% by one year, p=0.046). Taking 5-ARI, along with vaccination in patients with prostatic hyperplasia is a protective factor for morbidity and the severity of COVID-19.


Evaluation of initial prostate cancer biopsies utilizing 3D open-top light-sheet microscopy for detection of early disease.
Open-top light-sheet (OTLS) microscopy is a technique that allows for high-resolution 3D imaging of tissue specimens and can therefore provide a more detailed assessment of tissue architecture. Given that Gleason grading is based on tissue architecture, we hypothesized that OTLS microscopy would enable us to survey a larger amount of tissue and detect occult prostate cancers in men who had prostate core biopsy specimens initially classified as being benign-appearing who later developed clinically significant prostate cancers. Benign appearing tissue (based on routine pathologic evaluation) from 20 patients who subsequently developed a clinically significant prostate cancer (experimental group) was evaluated with OTLS microscopy and compared to tissue from 20 patients who underwent prostate biopsy and never developed a clinically significant prostate cancer (control group). We compared the incidence of detectable prostate cancer between groups. Baseline clinical characteristics were similar between the experimental and control groups. Three patients (15%) in the control group and one (5%) in the experimental group had suspicious findings on low-resolution OTLS microscopy. Higher resolution OTLS imaging revealed two patients (10%) in the control group had an occult prostate cancer, while no occult cancers were found in the experimental group. In spite of a high pretest probability for the presence of an occult prostate cancer, we did not identify cancer in our experimental group. This may be due to under-sampling at the time of prostate needle biopsy.


IL-27 paves different roads to Tr1.
Tr1 cells are non-Foxp3-expressing regulatory CD4(+) T cells that execute suppressor functions by secreting the anti-inflammatory cytokine IL-10. Differentiation of this T-cell subset is facilitated by the heterodimeric cytokine IL-27, which can activate transcription factors such as c-Maf and Ahr to positively regulate the differentiation of Tr1 cells and their IL-10 production. In this issue of the European Journal of Immunology, an alternate transcriptional network regulated by IL-27 to induce IL-10 production in Tr1 cells is reported by Iwasaki et al. [Eur. J. Immunol. 2013. 43: 1063-1073]. This study shows that IL-27 initiates tandem activation of the transcription factors STAT3 and Egr-2 to induce il10 in Tr1 cells in a Blimp1-dependent fashion. These findings indicate a c-Maf/Ahr independent mechanism that activates IL-10 production by Tr1 cells and suggest that Il10 induction may depend on both the cytokine environment and the molecular context. Thus, Tr1 cells may be another example of the remarkable plasticity of CD4(+) T cells and indeed may not constitute a separate lineage of CD4(+) T cells but rather represent a developmental endpoint of several T helper cell differentiation pathways.


Biodegradable 3D Printed Scaffolds of Modified Poly (Trimethylene Carbonate) Composite Materials with Poly (L-Lactic Acid) and Hydroxyapatite for Bone Regeneration.
Biodegradable scaffolds based on biomedical polymeric materials have attracted wide interest in bone transplantation for clinical treatment for bone defects without a second operation. The composite materials of poly(trimethylene carbonate), poly(L-lactic acid), and hydroxyapatite (PTMC/PLA/HA and PTMC/HA) were prepared by the modification and blending of PTMC with PLA and HA, respectively. The PTMC/PLA/HA and PTMC/HA scaffolds were further prepared by additive manufacturing using the biological 3D printing method using the PTMC/PLA/HA and PTMC/HA composite materials, respectively. These scaffolds were also characterized by Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), automatic contact-angle, scanning electronic micrographs (SEM), diffraction of X-rays (XRD), differential scanning calorimetry (DSC), and thermogravimetry (TG). Subsequently, their properties, such as mechanical, biodegradation, cell cytotoxicity, cell compatibility in vitro, and proliferation/differentiation assay in vivo, were also investigated. Experiment results indicated that PTMC/PLA/HA and PTMC/HA scaffolds possessed low toxicity, good biodegradability, and good biocompatibility and then enhanced the cell multiplication ability of osteoblast cells (MC3T3-E1). Moreover, PTMC/PLA/HA and PTMC/HA scaffolds enhanced the adhesion and proliferation of MC3T3-E1 cells and enabled the bone cell proliferation and induction of bone tissue formation. Therefore, these composite materials can be used as potential biomaterials for bone repatriation and tissue engineering.


In vitro suppression of inflammatory cytokine response by methionine sulfoximine.
The glutamine synthetase inhibitor methionine sulfoximine (MSO), shown previously to prevent death caused by an inflammatory liver response in mice, was tested on in vitro production of cytokines by mouse peritoneal macrophages triggered with lipopolysaccharide (LPS). MSO significantly reduced the production of Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFα) at 4 and 6 h after LPS-treatment. This reduction did not result from decreased transcription of IL-6 and TNFα genes, and therefore appeared to result from post-transcriptional inhibition of synthesis of these cytokines. MSO treatment did not inhibit total protein synthesis and did not reduce the production of a third LPS-triggered cytokine CXCL1, so the effect was not a toxic or global downregulation of the LPS response. The anti-inflammatory effects of a glutamine synthetase inhibitor were seen even though the medium contained abundant (2 mM) glutamine, suggesting that the target for this activity was not glutamine synthetase. In agreement with this hypothesis, the L,R isomer of MSO, which does not inhibit glutamine synthetase and was previously thought to be inert, both significantly reduced IL-6 secretion in isolated macrophages and increased survival in a mouse model for inflammatory liver failure. Our findings provide evidence for a novel target of MSO. Future attempts to identify the additional target would therefore also provide a target for therapies to treat diseases involving damaging cytokine responses.


[The postnatal contraception: upon 600 patients of whom 129 were postnatal controlled].
To draw a parallel between the contraceptive methods prescribed in the post-natal ward and the contraceptive methods taken by patients during their postnatal visit. This piece of work draws information from a prospective 10 weeks study at a University Teaching Hospital post-natal ward on the contraception that is prescribed upon leaving the maternity ward and also at the time of the post-natal visit. From the 600 cases studied, the analysis is about 129 patients reviewed in the post-natal visit. The percentage of loss was 78.5%. A hormonal contraceptive pill was prescribed to 73.5% of women (441 patients) after birth in which 63.5% had microprogestative pills. At the earliest, the IUD was given at about 5.4 weeks postpartum. At the time of the postnatal visit, compliance was bad for one third of women with either estrogen plus progestin methods, microprogestative or natural methods. Women who chose a barrier method were only 45.5% to follow this choice, the others left without contraception. The prescription of postpartum contraception was followed by only 66.6% of women. In order to prescribe a more effective contraceptive method, we must improve the prescriber's timing in sharing contraceptive information and completeness of the contraceptive methods offered.


Proprioception and functional deficits of partial meniscectomized knees.
The partial meniscectomy leads to proprioceptive knee deficits in a short period after the arthroscopic procedure; however, to our knowledge, a limited number of studies have investigated the long-term outcomes of partial meniscectomy on the knee joint proprioception. The aim of the present study was to assess the proprioception and muscle function of the partial meniscectomized knee through balance and functional tests 1-2 years posterior to arthroscopic surgery. This was an observational study. Partially meniscectomized persons after 1-2 years. Twenty-six male patients who had an arthroscopic partial meniscectomy at the age between 20-40. All patients performed balance (Biodex Stability System and balance boards) and functional (triple jump) tests. On the balance system the deviations from the horizontal plane were recorded, on the balance boards their performance was timed, and on the functional test triple jump their performance was recorded in meters. One-way Anova was used to determine significant differences between the healthy and injured limb. The level of statistical significance was set at p<0.05. The results revealed significant differences (p<0.05) between the healthy and injured limb at all balance and functional tests performed. The present study demonstrated that 1-2 years after partial meniscectomy, patients had reduced proprioception and knee muscular ability in the operated leg compared to the non-operated leg. Clinical rehabilitation impact. Proprioception and knee muscular ability deficits significantly affect objective knee function, indicating the importance not only of the restoring muscle function but also of the proprioception ability in partial meniscectomy patients.


Effect and Process Evaluation of an Intervention to Improve Hand Hygiene Compliance in Long-Term Care Facilities.
This study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change. We conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback). The study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands. Hand hygiene compliance was observed during 5 measurement periods using WHO's "Five Moments for Hand Hygiene." Multilevel analyses and corresponding tests were completed on an intention-to-treat basis. The absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P < .001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P < .002) before a clean and aseptic procedure, 18% (95% CI 10-26, P < .001) after touching a resident, 14% (95% CI 7-22, P < .003) before touching a resident, 10% (95% CI 5-15, P < .001) after contact with body fluid, and 1% (95% CI -11 to 13, P = .8) after touching a resident's surroundings. With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores. Our strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance.


The relationship between enthesitis indices and disease activity parameters in patients with ankylosing spondylitis.
In this study, patients with ankylosing spondylitis (AS) were assessed both by patient and physician using two enthesitis indices and the relationship between these indices and disease activity parameters was investigated. The study involved 100 AS patients. The patients were evaluated with 10-cm visual analog scale (VAS) for spinal pain (VAS-S), peripheral joint pain (VAS-P), global assessment of patient, and global assessment of doctor. In the laboratory evaluations, the erythrocyte sedimentation rates (ESR) and serum C-reactive protein levels of the patients were determined. Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index, and Bath AS radiology index were calculated. The severity of enthesitis was evaluated according to Mander enthesitis index (MEI) and Maastricht ankylosing spondylitis enthesitis score applied by both the patient (MASES-P) him/herself and the physician (MASES-D). There was a correlation between BASDAI and BASFI as well as MEI, MASES-D, and MASES-P indices (r = 0.447, r = 0.342, r = 0.663, r = 0.530, r = 0.464, and r = 0.435, respectively). No correlation between the laboratory parameters and enthesitis indices were detected. In multiple linear regression analysis, BASFI, VAS-S, and female gender (41.3%) were the best predictors of MEI-D, whereas BASFI, VAS-S, female gender, and ESR (32.5%) were the best predictors for MASES-D and BASFI (18.9%) was the best predictor of MASES-P. The assessment of simple and easily applicable MASES score by a patient may be expected to help the physician in clinical practice. When the disease activity of the patients with AS are evaluated, both BASDAI, the clinical importance of which has been confirmed in numerous studies and which is recommended by ASAS, and BASFI, which is valued by patients, should be considered.


JIA in 2011: New takes on categorization and treatment.
In 2011, new treatment recommendations for juvenile idiopathic arthritis (JIA) were proposed, inroads were made towards understanding the heterogeneity of this disease, and data were presented demonstrating the potential efficacy of DMARD combination therapies for JIA treatment. These advances hold promise for improved management of JIA in 2012 and beyond.


Diagnostic and prognostic values of pyroptosis-related genes for the hepatocellular carcinoma.
Due to the high heterogeneity, the early diagnosis and prognostic prediction of hepatic cellular cancer (HCC) is challenging. In this study, we explored the diagnostic and prognostic value of pyroptosis-related genes (PRGs) in HCC. We downloaded the mRNA expression profiles of HCC and the corresponding clinical data from the TCGA and ICGC databases. Fifty-one PRGs were extracted from Genecards, MsigDB, and relevant literature. The area under the receiver operating characteristic (AUC) was used to explore the diagnostic value of the PRGs. The results revealed that BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC, and GSDMD had higher diagnostic values for HCC (AUCs > 0.8, P < 0.05). Then, univariate and multivariate analyses of 51 PRGs were performed for HCC samples, and 4 PRGs (TP53, GPX4, GSDMC, BAK1) associated with HCC prognosis were obtained and used to construct a pyroptosis-related risk model. HCC samples were divided into high-risk and low-risk groups based on the risk score's cut-off. Kaplan-Meier curve and Log-rank test were used to compare the overall survival (OS) of two risk groups. The OS was lower in the high-risk group than in the low-risk group. In addition, the time-dependent receiver operating characteristics revealed that the risk model could be used to predict the prognosis of HCC more accurately. The risk score also resulted as an independent risk factor for HCC prognosis (TCGA: HR = 2.45, 95% CI 1.53-3.92; ICGC: HR = 2.19, 95% CI 1.39-3.46). Moreover, the AUC of the risk score for diagnosing HCC was relatively higher (TCGA: AUC = 0.840, P < 0.05; ICGC: AUC = 0.795, P < 0.05). In a word, BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC, GSDMD, and the pyroptosis-related risk model could be used to diagnose the HCC, and the risk score also resulted as an independent risk factor for the HCC prognosis.


Hemifacial spasm. Results of unilateral myectomy.
Hemifacial spasm (HFS) is a disorder characterized by unilateral involuntary spasm of the muscles innervated by the facial nerve (cranial nerve VII). The etiology is often a redundant or ectatic artery in the cerebellopontine angle that compresses the facial nerve. Neurosurgical decompression with implantation of a sponge between the ectatic artery and the facial nerve produces good results, but has a high complication rate and a poor patient acceptance rate. Various modes of peripheral neurectomy have also been advocated, but the recurrence rate is high and the preexisting functional and cosmetic eyelid deformities are exacerbated. The results of unilateral periorbital myectomy in 21 HFS patients are presented. Follow-up ranging from 1 to 7 years was available on 16 patients. Excellent or good results were obtained in 94% of these cases, and postoperative complications were minor. Transient lymphedema and forehead anesthesia are the most common complications. An unforseen benefit of periorbital myectomy surgery is the improvement or relief of lower facial contractions that occurred in 75% of patients. The authors believe the myectomy procedure is a safe, effective, predictable therapy for those HFS patients unwilling to risk a neurosurgical operation, and allows simultaneous reconstruction of associated eyelid and eyebrow deformities.


New look at epiphrenic diverticula.
Twenty-five patients with epiphrenica diverticula were studied to clarify the mechanism for esophageal regurgitation and to evaluate methods of treatment. Esophagogastroduodenoscopy, esophageal motility, and cineradiographic studies were performed. With probes in the tubular esophagus and diverticula of two patients, motility and cineradiographic studies were performed simultaneously to correlate symptoms and pressure changes with movement of diverticular and esophageal contents. Nineteen patients were operated, and six relatively asymptomatic patients were not. There was no operative mortality, and the one esophageal fistula that occurred healed spontaneously. Results were excellent or good in 10 operated patients followed long term after resection or imbrication of the diverticula. Eight patients did not undergo myotomy. Results in four of these patients followed long term were excellent. Retrograde movement of diverticular contents into the esophagus depends on pouch volume and a pressure gradient between the pouch and the tubular esophagus after an esophageal contraction wave in the tubular esophagus has dissipated. The height of esophageal reflux and resulting symptoms depend on these factors and the lower esophageal sphincter pressure (LESP). Asymptomatic patients with an epiphrenic diverticulum do not require operation. Resection or imbrication of a diverticulum are the operative methods of treatment. We prefer the abdominal approach when this is possible. Myotomy in contraindicated when gastroesophageal reflux exists or the LESP is below normal.


A mannose-sensing AraC-type transcriptional activator regulates cell-cell aggregation of Vibrio cholerae.
In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.


Integrating genome-wide association studies with selective sweep reveals genetic loci associated with tolerance to low phosphate availability in Brassica napus.
Oilseed rape (Brassica napus L.; B. napus) is an important oil crop worldwide. However, the genetic mechanisms of B. napus adaptations to low phosphate (P) stress are largely unknown. In this study, a genome-wide association study (GWAS) identified 68 SNPs significantly associated with seed yield (SY) under low P (LP) availability, and 7 SNPs significantly associated with phosphorus efficiency coefficient (PEC) in two trials. Among these SNPs, two, chrC07__39807169 and chrC09__14194798, were co-detected in two trials, and BnaC07.ARF9 and BnaC09.PHT1;2 were identified as candidate genes of them, respectively, by combining GWAS with quantitative reverse-transcription PCR (qRT-PCR). There were significant differences in the gene expression level of BnaC07.ARF9 and BnaC09.PHT1;2 between P-efficient and -inefficiency varieties at LP. SY_LP had a significant positive correlation with the gene expression level of both BnaC07.ARF9 and BnaC09.PHT1;2. BnaC07.ARF9 and BnaA01.PHR1 could directly bind the promoters of BnaA01.PHR1 and BnaC09.PHT1;2, respectively. Selective sweep analysis was conducted between ancient and derived B. napus, and detected 1280 putative selective signals. Within the selected region, a large number of genes related to P uptake, transport, and utilization were detected, such as purple acid phosphatase (PAP) family genes and phosphate transporter (PHT) family genes. These findings provide novel insights into the molecular targets for breeding P efficiency varieties in B. napus. The online version contains supplementary material available at 10.1007/s11032-023-01399-9.


[Fencing for promoting health after breast cancer].
Physical activity is recommended after breast cancer surgery. Fencing is a sport that is well suited to combatting fatigue, pain and reduced arm mobility. A healthcare executive, herself a fencer, puts the benefits of this sport into perspective, both physically and psychologically.


Comparison of Nottingham Prognostic Index, PREDICT and PrognosTILs in Triple Negative Breast Cancer -a Retrospective Cohort Study.
Triple-negative breast cancer (TNBC) represents a heterogenous subtype of breast cancer with generally poor prognosis. The prediction of its prognosis remains essential to clinicians in their therapeutical decision-making process. The aim of our study was to compare the validity of three multivariable analysis derived prognostic systems, the Nottingham Prognostic Index (NPI), PREDICT and PrognosTILs (a prognosticator including tumor infiltrating lymphocytes, TILs) in a series of TNBCs. Patients operated on with TNBC at the Department of Surgery, Bács-Kiskun County Teaching Hospital, Kecskemét between 2005 and 2016 were included. Clinical and pathological parameters and follow-up data were collected from medical charts. TILs were assessed retrospectively, following international recommendations. Estimated survivals of PrognosTILs, PREDICT and NPI were recorded and compared with real outcomes. Altogether 136 patients were included in this retrospective study. In univariate Cox analysis, type of surgery, pT, pN, stage, NPI and type of adjuvant therapy were the significant prognostic variables. The multivariate Cox-regression strengthened that NPI is an independent predictor of overall and disease-free survivals in TNBCs. The NPI, PREDICT and PrognosTILs could be compared directly only in a ROC curve analysis: the sensitivities and specificities of these predicting systems are rather similar with area under the curve values falling between 0.7 and 0.8, and NPI having the highest values. Our findings reflect the diverse prognosis of TNBC and highlight the difficulties of predicting its outcome. None of the three multivariable prognosticators is inferior to the others, the NPI can reliably be used for TNBCs.


User Centered Design to Improve Information Exchange in Diabetes Care Through eHealth : Results from a Small Scale Exploratory Study.
Heterogeneity of people with diabetes makes maintaining blood glucose control and achieving therapy adherence a challenge. It is fundamental that patients get actively involved in the management of the disease in their living environments. The objective of this paper is to evaluate the use and acceptance of a self-management system for diabetes developed with User Centered Design Principles in community settings. Persons with diabetes and health professionals were involved the design, development and evaluation of the self-management system; which comprised three iterative cycles: scenario definition, user archetype definition and system development. A comprehensive system was developed integrating modules for the management of blood glucose levels, medication, food intake habits, physical activity, diabetes education and messaging. The system was adapted for two types of principal users (personas): Type 1 Diabetes user and Type 2 Diabetes user. The system was evaluated by assessing the use, the compliance, the attractiveness and perceived usefulness in a multicenter randomized pilot study involving 20 patients and 24 treating professionals for a period of four weeks. Usage and compliance of the co-designed system was compared during the first and the last two weeks of the study, showing a significantly improved behaviour of patients towards the system for each of the modules. This resulted in a successful adoption by both type of personas. Only the medication module showed a significantly different use and compliance (p= 0.01) which can be explained by the different therapeutic course of the two types of diabetes. The involvement of patients to make their own decisions and choices form design stages was key for the adoption of a self-management system for diabetes.


Prepared for survivorship? Multidisciplinary healthcare professionals' experiences with adolescents' transition off cancer treatment: A focus group study.
Research indicates that re-entering everyday life after completed cancer treatment can be challenging for adolescents, and knowledge about how healthcare professionals prepare them is scarce. This study explored (a) healthcare professionals' experiences with adolescents with cancer transitioning off active cancer treatment; and (b) what healthcare professionals' do to prepare adolescents and their families for this transition; and c) their ideas to improve current practice. We conducted 8 focus-group interviews with 56 multidisciplinary healthcare professionals working in paediatric oncology settings across Norway. The sample consisted of nurses, physicians, social workers, psychologists, physiotherapists, a nutritionist, a dentist, a teacher and a music therapist. Inductive thematic analyses was used. We identified three main themes: (a) the multifaceted nature of the end of the treatment phase; (b) navigating challenges in providing early survivorship care; and (c) healthcare professionals' views and wishes regarding their role in transition care. The healthcare professionals conveyed uncertainty regarding how and when to talk about survivorship during treatment. Post-treatment, healthcare professionals' challenges included time restrictions, meeting the families' individual information needs and providing tailored psychosocial care. Suggestions for improvements included checklists, defined roles and dedicated transition consultations. Healthcare professionals were aware of the challenges families face during transition, and felt many were not addressed adequately. Although they had similar concrete suggestions for improvements, system barriers and lack of time and focus on survivorship were seen to hamper implementation. Implementing a standardized transition programme with increased nurse involvement could potentially improve the transition phase for everyone involved.


Utilizing dual functions of LaPO4to enhance the electrochemical performance of LiNi0.87Co0.09Al0.04O2cathode material.
In this paper, via a facile wet coating method, the LaPO4coating layer has been introduced onto the LiNi0.87Co0.09Al0.04O2(NCA) surface while a small part of La3+has also been doped on the surface to realize the dual functions modification of coating and doping. The morphology and structure of the samples were investigated by XRD, SEM and TEM measurements. The chemical compositions of the samples were analyzed via EDS and XPS data. The results showed that the coating of LaPO4and the doping of La3+were successfully achieved on the surface of NCA. Electrochemical tests indicate that the sample modified with 2 wt% LaPO4(L2-NCA) possesses the best electrochemical performance. After 100 cycles, compared with the capacity retention rate of pristine NCA of 87.1%/74.2% at 0.5 C at 25 °C/60 °C, L2-NCA showed better cycling stability, and the capacity retention rate increased to 96.0%/85.1%, respectively. Besides, the rate performance of the modified samples at 1 C, 2 C and 5 C were also significantly improved. These satisfactory results reveal that the surface modification of LaPO4provides a feasible scheme to uprate the performance of Ni-rich cathode materials.


Regulation of human eye growth by the energy density of the radiation in the retina--a biophysical theory in ophthalmology.
A number of theoretical and experimental models analyze regulation of eye growth in humans and animals. In this article we introduce a biophysical theory to explain human eye growth from an energetic point of view. We find different energy densities of the electromagnetic radiation in the retina for hyperopic, emmetropic and myopic eyes. We postulate a relation between the different energy densities of the radiation in the retina and growth regulation by the retina. Based on this relation between physics and biology we are modeling emmetropization, missing emmetropization in severe hyperopia and development and progression of myopia in correspondence with a number of clinical and experimental results.


CPSF3 Promotes Pre-mRNA Splicing and Prevents CircRNA Cyclization in Hepatocellular Carcinoma.
CircRNAs are crucial in tumorigenesis and metastasis, and are comprehensively downregulated in hepatocellular carcinoma (HCC). Previous studies demonstrated that the back-splicing of circRNAs was closely related to 3'-end splicing. As a core executor of 3'-end cleavage, we hypothesized that CPSF3 modulated circRNA circularization. Clinical data were analyzed to establish the prognostic correlations. Cytological experiments were performed to determine the role of CPSF3 in HCC. A fluorescent reporter was employed to explore the back-splicing mechanism. The circRNAs regulated by CPSF3 were screened by RNA-seq and validated by PCR, and changes in downstream pathways were explored by molecular experiments. Finally, the safety and efficacy of the CPSF3 inhibitor JTE-607 were verified both in vitro and in vivo. The results showed that CPSF3 was highly expressed in HCC cells, promoting their proliferation and migration, and that a high CPSF3 level was predictive of a poor prognosis. A mechanistic study revealed that CPSF3 enhanced RNA cleavage, thereby reducing circRNAs, and increasing linear mRNAs. Furthermore, inhibition of CPSF3 by JET-607 suppressed the proliferation of HCC cells. Our findings indicate that the increase of CPSF3 in HCC promotes the shift of pre-mRNA from circRNA to linear mRNA, leading to uncontrolled cell proliferation. JTE-607 exerted a therapeutic effect on HCC by blocking CPSF3.


Goal congruency without stimulus congruency in bimanual coordination.
Two experiments explored the role of stimulus congruency and goal congruency for the generation of object-oriented actions with two hands. Participants had to place two objects into either parallel or opposite orientations by carrying out either symmetrical or asymmetrical forearm rotations. Performance was superior when the required object orientations were identical rather than different, almost independent of the symmetry of the required arm movements. In extending previous research, goal congruency effects ensued even under conditions in which congruency of imperative response signals could not have contributed to goal congruency effects, either because only a single stimulus was used to indicate the required goals in an individual trial (Experiment 1) or such stimuli were absent at all (Experiment 2). The results thus confirm the importance of goal codes for the reconcilableness of bimanual actions, and rule out accounts in terms of stimulus-related processes.


Expression and copper binding studies of a Plasmodium falciparum protein with Cox19 copper binding motifs.
Copper can exist in an oxidized and a reduced form, which enables the metal to play essential roles as a catalytic co-factor in redox reactions in many organisms. Copper confers redox activity to the terminal electron transport chain cytochrome c oxidase protein. Cytochrome c oxidase in yeast obtains copper for the CuB site in the Cox1 subunit from Cox11 in association with Cox19. When copper is chelated in growth medium, Plasmodium falciparum parasite development in infected red blood cells is inhibited and excess copper is toxic for the parasite. The gene of a 26 kDa Plasmodium falciparum PfCox19 protein with two Cx9C Cox19 copper binding motifs, was cloned and expressed as a 66 kDa fusion protein with maltose binding protein and affinity purified (rMBP-PfCox19). rMBP-PfCox19 bound copper measured by: a bicinchoninic acid release assay; an in vivo bacterial host growth inhibition assay; ascorbate oxidation inhibition and differential scanning fluorimetry. The native protein was detected by antibodies raised against rMBP-PfCox19. PfCox19 binds copper and is predicted to associate with PfCox11 in the insertion of copper into the CuB site of Plasmodium cytochrome c oxidase. Characterisation of the proteins involved in Plasmodium spp. copper metabolism will help us understand the role of cytochrome c oxidase and this essential metal in Plasmodium homeostasis.


Hallervorden-Spatz disease.
We had the opportunity to study a family, five of whose members were affected by the Hallervorden-Spatz disease (three males and twin girls). The characteristics of the condition were analyzed and compared with those cases considered by other authors to be affected by the condition. Intrafamilial and interfamilial variations were analysed, and it was the latter that contributed most to the overall variation of the condition. It was clearly established from the reported cases and our family that this is an autosomal recessive condition (P greater than 0.23 +/- 0.08). It is suggested that the condition probably originated in Europe and that it is caused by an inborn error of metabolism related to neuromelanin and the dopaminergic system. The condition affects the muscular tone and voluntary movements progressively, making voluntary coordinated movements, and chewing and swallowing almost impossible, and in the last part of its development mental deterioration, emaciation, severe feeding difficulties and visual impairment are common clinical manifestations. The ages of both onset and death are distributed in a unimodal curve. The mean survival time after diagnosis was 11.18 +/- 7.8 years.


Inverse relationship between the flagella formation and prodigiosin synthesis in Serratia marcescens.
Treatment by polymyxin B sulfate and ethylenediaminetetraacetate separated a 40 kilodalton (kDa) protein from the nonpigmented Serratia marcescens and even from the nonpigmented bacteria of the pigmented strains, whereas the same treatment separated the 100 kDa protein associated with the pigment formation from the pigmented bacteria. Lysozyme treatment separated the 100 kDa and/or 40 kDa proteins correlated with the pigmented level. The 40 kDa protein was not an outer membrane protein but a flagellin. These results suggest that the flagella formation was inversely related with the pigment formation.


'Sepsis' and multi-organ failure: predictors of poor outcome after hematopoietic stem cell transplantation in children.
Prognostic scores, such as the PRISM and APACHE II, have been established, predicting with reasonable accuracy the outcome of patients admitted to intensive care units (ICU). In keeping with previous reports, we found, however, that these scores failed to perform in a series of 28 recipients of hematopoietic auto- or allografts (BMT) who required ICU admission for reasons including respiratory (82%) and multi-organ (36%) failure. We therefore retrospectively analyzed the charts of these patients, evaluating predisposing factors and prognostic variables which might confound the validity of these ICU tools which in other clinical scenarios have proven so valuable. Of all the parameters tested, logistic analysis established the following as predictors for poor outcome: increased C-reactive protein (CRP) to > 10 mg/dl (P = 0.04), macroscopic hemorrhage (P = 0.04), hypotension (mean arterial pressure < normal) (P = 0.04) and GVHD > or = III (P = 0.002). Most of these factors are not accounted for by the standard prognostic questionnaires. The development of an 'oncological' or 'post-BMT' risk of mortality score, taking into account these patients' specific clinical problems, might improve the risk assessment for this patient group, and might thus facilitate the timely recognition of those patients most in need of more intensive therapeutic measures.


[Gene cloning and expression of human soluble interleukin-6 receptor in insect cells].
To clone the human soluble interleukin-6 receptor(hsIL-6R) gene and expression in insect cell line. The hsIL-6R gene was cloned into plasmid pAcGP67B. After co-transfection of recombinant plasmid and wild type AcNPV DNA, the rAcNPV was confirmed by the end point dilution assay and dot blot. Then it was purified by plaque assay. SDS-PAGE showed molecular weight of the expressed product was about 47,000. The expressed recombinant protein was confirmed to be specific and capable of binding its ligand IL-6 by Western blot and ligand-receptor binding assays. Secretory expression of hsIL-6R gene in baculovirus expression system was indicated. The expressed product had immunological and biological activities.


Prognostic significance of D-dimer, natural anticoagulants and routine coagulation parameters in acute pancreatitis.
This study was conducted to assess the predictive value of coagulation abnormalities in determining disease severity and prognosis of acute pancreatitis (AP). Patients of AP and 25 healthy volunteers were included in this prospective observational study. The final outcomes were disease severity assessed by Computed Tomography Severity Index, Acute Physiological Assessment and Chronic Health Evaluation--II, presence of organ failure and mortality. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen, antithrombin-III (AT-III), protein-C, and protein-S levels were assessed on day 0, 3 and 7 of admission. Of the 38 patients included, 13 died. Mean PT and TT were similar between patients and controls on any given day. PTT showed elevation on day 3 and 7 (p = 0.001) compared to controls, although fibrinogen and D-dimer were significantly higher in patients on all days. Protein C and AT-III were significantly lower in patients and more so in non survivors ( (p = 0.001)) than controls. Multiple logistic regression analysis revealed D-dimer levels > or = 400 - 800 ng/ml and AT- III level of < 71% at admission were associated with high mortality (OR 11.2, AUROC 0.70 and OR 16.6, AUROC 0.82 respectively) as well as predicted organ failure. Serum D-dimer and antithrombin-III levels can be used to assess disease severity and predict outcome of patients with acute pancreatitis.


The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes.
We have previously shown that NADPH oxidase (NOX) lies upstream of uncoupled endothelial nitric oxide synthase (eNOS), which is known to occur in diabetic endothelium. However, it remains unclear which specific NOX isoform(s) is responsible for eNOS uncoupling and endothelial dysfunction in diabetic mouse models. The aim of the present study was to test the hypothesis that one or more NOX isoform(s) mediate(s) diabetic uncoupling of eNOS, which has been shown to occur in patients with diabetes to contribute to endothelial dysfunction. Diabetes was induced by streptozotocin administration. The N (ω)-nitro-L-arginine methyl ester (L-NAME)-sensitive superoxide production of aortic segments, reflective of eNOS uncoupling activity, was determined by electron spin resonance. The L-NAME-sensitive superoxide production was more than doubled in wild-type diabetic mice, implicating uncoupling of eNOS. This was abolished in diabetic p47 ( phox-/-) (also known as Ncf1 (-/-)) mice, but preserved in Nox2 (-/y) (also known as Cybb (-/-)) mice made diabetic. The eNOS uncoupling activity was markedly attenuated in diabetic mice transfected with Nox1 or Nox1 organiser 1 (Noxo1) short interfering RNA (siRNA), and abolished in Nox1 (-/y) diabetic mice. Diabetes-induced impairment in endothelium-dependent vasorelaxation was also significantly attenuated in the Nox1 (-/y) mice made diabetic. By contrast, Nox4 siRNA, or inhibition of mitochondrial complex I or III with rotenone or siRNA, respectively, had no effect on diabetic uncoupling of eNOS. Overexpression of Dhfr, or oral administration of folic acid to improve dihydrofolate reductase (DHFR) function, recoupled eNOS in diabetes to improve endothelial function. Our data demonstrate for the first time that the p47(phox) and NOXO1-dependent activation of NOX1, but not that of NOX2, NOX4 or mitochondrion, mediates diabetic uncoupling of eNOS. NOX1-null mice are protected from diabetic endothelial dysfunction. Novel approaches to inhibit NOX1 and/or improve DHFR function, may prove to have therapeutic potential for diabetic endothelial dysfunction.


GABA(B) receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses.
Activity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. We found that long-term modification of developing rat hippocampal GABAergic synapses that was induced by repetitive coincident pre- and postsynaptic spiking was also frequency dependent. Spiking at 20-50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABA(B) receptors (GABA(B)Rs), whereas the depression was independent of GABA(B)R activation and could be converted to potentiation by elevating GABA(B)R activity. The potentiation could be attributed to a local postsynaptic increase in Na(+)/K(+)/2Cl(-) co-transporter activity near activated synapses. The activity of postsynaptic Ca(2+)/calmodulin-dependent protein kinase II was necessary for long-term potentiation of these developing GABAergic synapses and its phosphorylation at Thr286 could be enhanced by activating GABA(B)Rs with baclofen. Together with our finding that activation of GABA(B)Rs is frequency dependent, these results indicate that postsynaptic GABA(B)R activation mediates frequency-dependent potentiation of developing GABAergic synapses.


Energy Conservation/Envelope Theory Interventions to Help Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Treatment approaches for patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been controversial. This paper provides the theoretical and conceptual background for the Energy Envelope Theory to assist patients with ME/CFS and reviews evidence of its treatment efficacy. Over a 15-year period, efforts were directed to develop a non-pharmacologic intervention that endeavored to help patients with ME/CFS self-monitor and self-regulate energy expenditures and learn to pace activities and stay within their energy envelope. Studies show that the energy envelope approach, which involves rehabilitation methods, helps patients with ME/CFS pace activities and manage symptoms and can significantly improve their quality of life.


Money makes the (medical assessment) world go round: The cost of components of a summative final year Objective Structured Clinical Examination (OSCE).
The widely used Objective Structured Clinical Examination (OSCE) is undoubtedly expensive. Cost-effectiveness is one of the components of the assessment utility index defining its usefulness. Our current financial climate demands increased transparency in the costs associated with medical education and it is now vital to ascertain how much is spent on assessments, such as the OSCE, and in particular costs associated with the different types of stations within the OSCE. A retrospective case-study approach was used to identify all costs associated with the development, production, administration and post-examination phases of the 2013 final year MBChB OSCE at the University of Aberdeen, Scotland. This 15 station OSCE was held over 2 days for 185 students. This OSCE cost £65,328 to run. Costs per station ranged from £3108 (prescribing) to £6577 (eye examination). The cost per student was £355. The costs of a "high stakes" OSCE are sobering. The bulk of costs identified are not modifiable in light of what is currently known about the metrics of OSCE utility, particularly reliability and validity. Providers, and funders, of medical education must be prepared to assign significant resource to OSCE assessment and centres should be encouraged to calculate precise costs associated with assessment to inform resource allocation decisions.


Use of the deltoid branch-based clavicular head of pectoralis major muscle flap in isolated sternoclavicular infections.
The pectoralis major (PM) flap is the workhorse flap for acute, sub-acute and chronic sternoclavicular infections (SCIs). Attempts at using only the clavicular head of the pectoralis major muscle (CPM), based on internal mammary perforators or the thoracoacromial artery, have been reported. We describe the harvest of a deltoid branch-based flap (CPM-DTA) and examine its use in managing a series of isolated, acute and sub-acute sternoclavicular infections. From 2007 to 2012, 28 subjects with SCI underwent PM flaps at our institution. Six were excluded for extensive chest wall involvement, and four were excluded from chronic osteomyelitis (5 months of infection or greater). Of the remaining 18 patients with isolated SCI, 12 underwent traditional PM flaps (Group-A), while six underwent CPM-DTA (Group-B). Features studied include age, gender, co-morbidities, culture, need for intra-operative extension of the sternoclavicular incision, postoperative complications, wound healing, time from infection onset to debridement, length of hospital stay, postoperative chest wall contour deformity and follow-up. Infections resolved and wounds healed in all patients following a single reconstructive procedure. Intra-operative need for extended incisions and postoperative ipsilateral anterior chest wall contour deformity are noted in all Group-A subjects but in no Group-B subjects. In patients with isolated, acute and sub-acute SCI, the CPM-DTA flap achieves effective wound closure while avoiding large sternal incisions and the morbidity associated with standard PM muscle harvest. Harvesting the CPM-DTA flap preserves the sternocostal head of the pectoralis major muscle and its thoracoacromial pedicle. This preserves the muscle for future flap use if necessary.


Identification of nonalcoholic fatty liver disease following pancreatectomy for noninvasive intraductal papillary mucinous neoplasm.
Nonalcoholic fatty liver disease (NAFLD) following pancreatectomy is a potential cause of long term morbidity in patients undergoing pancreatic resection with curative intent. Prior studies have reported an incidence of NAFLD up to 30% following pancreatectomy but the investigated cohorts were typically a mix of benign and malignant disease. Here we examined the incidence of NAFLD in a homogenous cohort of patients following pancreatectomy for benign intraductal papillary mucinous neoplasm (IPMN). A retrospective review of patients who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post pancreatectomy CT/MRI scans were obtained as standard surveillance. We investigated changes in the liver parenchymal density on post surgical imaging to estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were performed. Our study cohort included 109 patients who underwent pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up was 52 months (range 8-130/months). The incidence of postoperative NAFLD was 17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and development of atrophy of the pancreas remnant were significant risk factors for development of hepatic steatosis (p < 0.05). Patients undergoing pancreatectomy for benign disease have a significant risk of developing NAFLD but the frequency is lower than previously reported in cohorts that included individuals with malignant disease. Highest risk was observed in individuals who underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further investigations to define the mechanisms that promote steatosis and interventions to prevent subsequent morbidity from NAFLD are warranted.


Clinical performance of two different CAD/CAM-fabricated ceramic crowns: 2-Year results.
Recently, technical problems, especially chipping, have been reported for ceramic restorations; as a result, ceramic crowns produced entirely by computer-aided design and computer-aided manufacture (CAD/CAM) have become popular because the incidence of chipping is less. The purpose of this study was to report on 2-year results for 2 different types of CAD/CAM ceramic crowns placed in adult patients in a dental practice. Sixty participants who required a crown for a first or second molar were randomly assigned to 1 of 2 groups. Crowns in the veneered zirconia (VZ) group were made of zirconia frameworks veneered with CAD/CAM-produced lithium disilicate ceramic; the other group's crowns were made of monolithic lithium disilicate (MLD) ceramic. Each crown was reviewed after 2 weeks, 1 year, and 2 years by using modified the US Public Health Service (USPHS) criteria. Statistical analysis was performed by using the log-rank test, nonparametric tests, and Kaplan-Meier survival analysis. All 60 participants were recalled after 1 and 2 years. In the VZ group, 2 endodontic complications occurred, and deterioration of periodontal health was observed for 3 participants. In the MLD group, 2 endodontic complications occurred within 2 years. In both of the groups, no caries or marginal discoloration was observed. No technical complications, for example, cracks, chipping, or fractures, were detected after 2 years. The shape and appearance of all crowns were assessed positively by the examining dentist. The log-rank test showed no significant differences in respect to technical or biologic complications (P=.324). For both types of single-crown restoration, no technical failures occurred. The number of biological complications did not differ significantly between the types of crowns.


Decrement Evoked Potential (DEEP) Mapping of the Atria: Unmasking Atrial Fibrillation Substrate.
Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy. Consecutive patients referred for AF ablation were prospectively included at four institutions. Decrement evoked potential mapping (DEEP) was performed in eight left atrial sites and five right atrial sites, from two different pacing locations (endocardially from the left atrial appendage, epicardially from the proximal coronary sinus). The electrograms (EGMs) during S1 600 ms drive and after an extra stimulus (S2 at +30 ms above atrial refractoriness) were studied at each location and assessed for decremental properties. Follow-up was 12 months. Seventy-four patients were included and 85% had persistent AF. A total of 17,614 EGMs were individually analysed and measured. Nine percent of the EGMs showed DEEP properties (local delay of >10 ms after S2) with a mean decrement of 33±26 ms. DEEPs were more frequent in the left atrium than the right atrium (9.4% vs 8.0%; p<0.001) and more prevalent in persistent AF patients than paroxysmal AF patients (9.8% vs 4.6% p=0.001). Atrial DEEPs were more frequently unmasked in normal bipolar voltage areas and by epicardial pacing than endocardial pacing (9.6% vs 8.4%, respectively; p=0.004). Within the left atrium, the roof had the highest prevalence of DEEP EGMs. DEEP mapping of both atria is useful for highlighting areas with a tendency for unidirectional block and re-entry initiation. Those areas are more easily unmasked by epicardial pacing from the coronary sinus and more prevalent in persistent AF patients than in paroxysmal AF patients.


Motor control and children with autism: deficit of anticipatory function?
This study aims at investigating how do anticipatory postural adjustments develop in children with autism, during a bimanual load-lifting task that required maintaining the stabilisation of the forearm despite imposed or voluntary unloading. Elbow angle and electromyographic were recorded on the child forearm supporting the load. The forearm stabilisation was as good in children with autism as in the control group. However, in children with autism, the latencies for both kinematics and muscular events indicated an increase of the duration of unloading. These results indicate the use of a feedback rather than a feed-forward mode of control. Impairments in both the building of internal representations and the mastering of timing parameters, could explain the deficient postural anticipation reported in children with autism.


Balancing Quality, Intensity and Scalability: Results of a Multi-level Sexual and Reproductive Health Intervention for Very Young Adolescents in Kinshasa.
In addition to the rapid physical and cognitive transformations very young adolescents (VYAs) experience between ages 10-14, gender and social norms internalized during this period have long-term implications as adolescents become sexually active. This age presents critical opportunities for early intervention to promote gender-equitable attitudes and norms for improved adolescent health. In Kinshasa, DRC, Growing Up GREAT! implemented a scalable approach to engage in- and out-of-school VYAs, caregivers, schools, and communities. A quasi-experimental study evaluated the outcomes of sexual and reproductive health (SRH) knowledge, assets and agency, and gender-equitable attitudes and behaviors among VYA participants. Ongoing monitoring and qualitative studies provided insights into implementation challenges and contextual factors. Results show significant improvement in SRH knowledge and assets such as caregiver connectedness, communication, and body satisfaction among the intervention group. The intervention was also associated with significant improvements in gender-equitable attitudes related to adolescents' household responsibilities and decreased teasing and bullying. Intervention effects on awareness of SRH services, body satisfaction, chore-sharing, and bullying were stronger for out-of-school and younger VYAs, suggesting the intervention's potential to increase positive outcomes among vulnerable adolescents. The intervention did not shift key gender norm perceptions assessed. Implementation research suggests design decisions made to increase the intervention's scalability necessitated reductions in training and program dosing that may have affected results. Results affirm the potential of early intervention to increase SRH knowledge, assets and gender-equitable behaviors. They also highlight the need for more evidence on effective program approaches and segmentation for shifting VYA and SRH norms.


The multiaxial system of DSM-III: where did it come from and where should it go? II. Empirical studies, innovations, and recommendations.
In a companion report, the development of the DSM-III multiaxial system was described, as well as critiques that have been made of each of its five axes. In this report, empirical studies that provide information about the reliability and validity of the system are reviewed. In addition, suggestions that have been made for changes in the system are critically examined. Finally, this material is synthesized into specific proposals for improvements in the multiaxial system that will be considered by the recently constituted Work Group to Revise DSM-III.


Cytogenetic replication studies on murine T-cell leukemias with special consideration to chromosome 15.
Chromosomal replication was studied by means of the BrdU-Höchst-Giemsa-technique in three minute T-cell leukemias with special regard to chromosome 15. In all the three leukemic cell lines the normally early replicating band 15 E was undetectable whereas late replication in this region is completely unaltered. Furthermore, R-banding, the structural homologue of early replication banding, remains unchanged. This observation is interpreted as a shift in the time point of replication during the S-phase of region 15 E, though the exact timing of replication of this region in tumor chromosomes remains unresolved.


Skin lipid profiling in normal and seborrhoeic shih tzu dogs.
Seborrhoea is a clinical condition resulting in excessive lipid and/or scale on the skin and is a common and important skin disease of dogs. However, there is little information on the skin surface lipid composition of dogs with seborrhoea. To compare skin surface lipid profiles in normal and seborrhoeic shih tzu dogs. Fourteen client-owned dogs (seven seborrhoeic and seven normal) were investigated. Lipids in sebaceous glands (SGs) were extracted from homogenized tissues of SG hyperplasia. Surface lipid was collected by tape stripping [stratum corneum (SC)-enriched fraction] and acetone-wetted cotton swab (acetone-extracted fraction). Lipids in SGs, SC-enriched fractions and acetone-extracted fractions were evaluated by high-performance thin-layer chromatography. Lipids in SGs mainly consisted of cholesterol esters, wax esters and triglycerides, whereas lipids in the SC-enriched fraction mainly consisted of ceramides. The acetone-extracted fraction contained a mixture of lipid classes recognized in SG- and SC-enriched fractions. In seborrhoeic dogs, concentrations of wax esters and triglycerides in the acetone-extracted fraction were significantly higher than in control dogs (P = 0.0285). Amounts of total ceramides (in micrograms) per milligram of SC were not significantly different between the two groups (P = 0.5204). Interestingly, two unknown ceramide fractions, which accounted for 20% of the total ceramides, were recognized exclusively in seborrhoeic dogs. These results provide evidence that the skin surface lipid profiles are altered in shih tzu dogs with seborrhoea.


Tissue Doppler derived isovolumic acceleration in patients after atrial repair for dextrotransposition of the great arteries.
Ventricular dysfunction represents one of the major problems in the long-term follow-up of patients after atrial repair for dextrotransposition of the great arteries. We aimed to study the role of tissue Doppler derived isovolumic acceleration (IVA) to detect early myocardial dysfunction in these patients. Twenty-four patients with dextrotransposition of the great arteries (D-TGA) that underwent atrial repair (Senning procedure: n = 12; Mustard procedure: n = 12) in infancy were examined at the age of 21 [12-33] years (median [range]) using tissue Doppler analysis of IVA and peak systolic myocardial velocity at rest and during exercise. 12 age-matched healthy subjects served as controls. At rest, IVA and peak systolic myocardial velocity were reduced in the systemic ventricle (SV) of patients. IVA correlated with peak systolic myocardial velocity (r = 0.76, P < 0.001). During exercise, IVA, but not peak systolic myocardial velocity, increased significantly in the SV of patients (rest: 1.03 +/- 0.44 cm/sec(2); 1 W/kg: 1.80 +/- 1.22 cm/sec(2); 2 W/kg: 2.85 +/- 1.26 cm/sec(2)). In the subpulmonary ventricle, IVA was significantly lower in patients compared to the controls (patients: 1.45 +/- 0.49 cm/sec(2) vs. controls: 2.31 +/- 0.43 cm/sec(2), P < 0.05). IVA but not peak systolic myocardial velocity was able to discriminate between patients and healthy subjects. IVA is superior to peak systolic myocardial velocity to assess a reduction in functional reserve of both ventricles in patients after atrial repair for D-TGA.


High-flow nasal cannula oxygen in patients with haematological malignancy: a retrospective observational study.
Patients with haematological malignancies (HM) face high rates of intensive care unit (ICU) admission and mortality. High-flow nasal cannula oxygen (HFNCO) is increasingly used to support HM patients in ward settings, but there is limited evidence on the safety and efficacy of HFNCO in this group. We retrospectively reviewed all HM patients receiving ward-based HFNCO, supervised by a critical care outreach service (CCOS), from January 2014 to January 2019. We included 130 consecutive patients. Forty-three (33.1%) were weaned off HFNCO without ICU admission. Eighty-seven (66.9%) were admitted to ICU, 20 (23.3%) required non-invasive and 34 (39.5%) invasive mechanical ventilation. ICU and hospital mortality were 42% and 55% respectively. Initial FiO2 < 0.4 (OR 0.27, 95% CI 0.09-0.81, p = 0.019) and HFNCO use on the ward > 1 day (OR 0.16, 95% CI 0.04, 0.59, p = 0.006) were associated with reduced likelihood for ICU admission. Invasive ventilation was associated with reduced survival (OR 0.27, 95%CI 0.1-0.7, p = 0.007). No significant adverse events were reported. HM patients receiving ward-based HFNCO have higher rates of ICU admission, but comparable hospital mortality to those requiring CCOS review without respiratory support. Results should be interpreted cautiously, as the model proposed depends on the existence of CCOS.


The Tooth Crossing the Confinement of Mandible: An Unique Expression of Central Variety of Dentigerous Cyst.
Dentigerous cyst (DC) is the most common developmental cyst that occurs in either jaw with a reported frequency of 18.1% (Jones et al. J Oral Pathol Med 35:500-507, 2006). DC literally means a tooth bearing cyst, and it is named due to the fact the it is almost always associated with an impacted or unerupted tooth in the jaw. The most common tooth involved by DC is mandibular third molar, since it is most common tooth to get impacted, followed by mandibular canine, maxillary third molars and mandibular premolars and less commonly maxillary central incisor. However, the association of mandibular second molar is unusual with an incidence of about 1.1%. We report a case of a 28 years old male diagnosed with an impacted mandibular third molar associated with DC and its surgical management.


[Phenotypes of resistance to antibiotics of Acinetobacter baumannii. Impact on therapeutic orientation].
By studying the sensitivity to antibiotics of 74 Acinetobacter baumannii strains, four phenotype groups were distinguished. The resistance of one of them (11% of the strains) to imipenem, argues against the therapeutic attitudes that now prevail. From studies on the kinetics of bactericidal activity of antibiotics and there association we propose what should be done in the laboratory to provide help to the physician for the antibiotic choice.