Catheter ablation of inducible atrial flutter, in combination with atrial pacing and antiarrhythmic drugs ("hybrid therapy") improves rhythm control in patients with refractory atrial fibrillation.
Atrial flutter or tachycardia may coexist with atrial fibrillation [AF] and can be treated with ablation techniques in attempt to reduce the total AF burden. The role of ablation of latent atrial tachyarrhythmias elicited at electrophysiologic study in conjunction with atrial pacing and antiarrhythmic drugs in patients with refractory AF has not been evaluated. We evaluated the efficacy of catheter ablation of electrically induced atrial flutter or atrial tachycardia in improving rhythm control in patients with refractory AF. Consecutive patients with refractory AF, and spontaneous atrial flutter (Group 1) or without spontaneous atrial flutter (Group 2) underwent programmed stimulation in a baseline drug-free state. All patients had electrically induced atrial flutter or tachycardia. Radiofrequency ablation of the arrhythmia substrate was performed in all patients. Primary endpoints evaluated for patient outcome in both groups included maintenance of rhythm control and freedom from recurrent atrial tachyarrhythmias. Forty-three patients, with a mean age of 66 +/- 13 years were studied. Group 1 consisted of 22 patients while Group 2 had 21 patients. Ablation of the tricuspid valve-inferior venacaval isthmus was performed in 41 patients who had common atrial flutter induced at electrophysiologic study. Ablation of other atrial sites was performed in 8 patients with induced atypical flutter and 4 patients with induced atrial tachycardia. Ten of these patients had ablation of more than one arrhythmia. 17 patients (40%) had atrial pacing instituted and 28 patients remained on a class 1/3 antiarrhythmic drug. During a mean follow-up of 26 +/- 14 months, 33 patients (82.5%) remained in rhythm control. Actuarial analysis showed 96% of patients in rhythm control at 6 months, 94% at 12 months, and 90% at 24 months. Freedom from symptomatic AF recurrence was 64% at 6 months, 58% at 12 months, and 42% at 24 months. The outcome for both of these endpoints was similar for Group 1 and Group 2 (p = NS). The AF free interval increased significantly from 7+/- 9 days to 172 +/- 121 days (p < 0.01) after ablation. This increase was again similar in both the groups. In the 14 patients were who did not receive atrial pacing and who remained on the same class 1/3 antiarrhythmic drug, the AF free interval increased from 18 +/- 17 days to 212+/- 102 days (p < 0.01). We conclude that electrophysiologic studies can elicit latent atrial flutter or tachycardia in patients with refractory AF without spontaneous monomorphic atrial tachyarrhythmias. Catheter ablation of electrically induced atrial flutter or tachycardia either alone, or with atrial pacing and with antiarrhythmic drug may improve rhythm control and reduce AF recurrences. This is similar in patients with and without spontaneous atrial flutter and refractory AF.


[Role and importance of civil society organisations in the support of cancer screening].
Promotion of cancer screening programmes and provision of correct and comprehensive information to the general public are essential for achieving sufficient attendance at the program-mes and fulfilling their longterm function. Various NGOs and CSOs play a very important role in this field. The article provides an overview of the most visible activities and campaigns that spread information about cancer prevention and preventive examinations in the Czech Republic.


Regulation of parietal cell migration by gastrin in the mouse.
Recent studies suggest that gastrin regulates parietal cell maturation. We asked whether it also regulates parietal cell life span and migration along the gland. Dividing cells were labeled with 5'-bromo-2'-deoxyuridine (BrdU), and parietal cells were identified by staining with Dolichos biflorus lectin. Cells positive for D. biflorus lectin and BrdU were reliably identified 10-30 days after BrdU injection in mice in which the gastrin gene had been deleted by homologous recombination (Gas-KO) and wild-type (C57BL/6) mice. The time course of labeling was similar in the two groups. The distribution of BrdU-labeled parietal cells in wild-type mice was consistent with migration to the base of the gland, but in Gas-KO mice, a higher proportion of BrdU-labeled cells was found more superficially 20 and 30 days after BrdU injection. Conversely, in transgenic mice overexpressing gastrin, BrdU-labeled parietal cells accounted for a higher proportion of the labeled pool in the base of the gland 10 days after BrdU injection. Gastrin, therefore, stimulates movement of parietal cells along the gland axis but does not influence their life span.


Karyotypic diversity in the subfamily Eurytominae (Hymenoptera: Eurytomidae).
New data on the karyotype structure of five species of the subfamily Eurytominae are described, including the following species: Eurytoma rosae (2n = 20), E. robusta (n =7, 2n = 14), E. serratulae (n = 6, 2n = 12), E. compressa (2n = 10) and Sycophila biguttata (2n = 18). 2n = 10, 12 and 14 are reported for the first time for the Eurytominae, in which only 2n = 20 and 18 have been previously found. The taxonomic and phylogenetic implications of the new chromosomal information are discussed. Karyotypes containing ten subtelo/acrocentric chromosomes which gradually decrease in size can be considered as initial for the Eurytominae. Eurytoma robusta + (E. serratulae + E. compressa) form a particular clade where all branches are well-supported by morphological, biological and chromosomal apomorphies.


Maxillo-facial surgical approach: an introduction and review of mandibular advancement.
Patients afflicted with obstructive hypersomnia sleep apnea (HSA) have been treated traditionally with permanent tracheostomy. More recently, an association between HSA and mandibular retrognathism has been noted. Several centers have reported rapid reversal of HSA symptoms in retrognathic patients after mandibular advancement. Their experiences are outlined; the anatomy and pathophysiology leading to obstructive HSA are reviewed, and the recommendations for evaluation and patient management are discussed.


Neurological Complications after Renal Transplantation: A Retrospective Clinical Study.
The aim of this study was to evaluate the incidence and types of neurological complications (NCs) and associated factors in renal transplantation (RT) patients. Three hundred and forty-four patients who had RT performed at our institution between January 2005 and July 2014 were retrospectively evaluated. File records of the patients revealed 19 who experienced a total of 22 episodes of NCs, of whom three had more than one episode. The mean age of 19 patients included in the study, of whom eight were female, was 37.52±13.08 (range, 18-65) years. NCs were classified into central or peripheral depending on the location of involvement of the central nervous system (CNS). CNS involvement was found in 16 (84.2%) of the 19 patients. Tremor (36.8%) was the most common CNS complication in these patients. Encephalopathy, generalized tonic-clonic seizures, and status epilepticus were observed in two patients (10.5%). Delirium and dementia were observed in one patient (5.2%). Headache was experienced by one patient, and agitated depression was observed in one patient. Six patients (26.3%) had the peripheral nervous system involvement. One patient had the numbness of hands with normal electromyography findings, and four patients had polyneuropathy. In one patient, lumbar plexopathy was observed. Seventeen of the 22 NCs were considered to be caused by immunosuppressive agents. Each incidence of amyloidosis, infection, septic emboli, and hypoglycemia caused a neurological episode. The etiology of one episode was unknown. Different neurological disorders can be seen after RT, and most of them are caused by immunosuppressive drugs. NCs seen after RT can be treated by decreasing the dose or changing the immunosuppressive drug.


Maternal metabolic stress may affect oviduct gatekeeper function.
We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24-h treatments at Day 9: (1) control (0 µM NEFA + 0% EtOH), (2) solvent control (0 µM NEFA + 0.45% EtOH), (3) basal NEFA (720 µM NEFA + 0.45% EtOH in the basal compartment) and (4) apical NEFA (720 µM NEFA + 0.45% EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment and related to transepithelial electric resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA uptake were studied using Bodipy 493/503 and immunolabelling of FA transporters (FAT/CD36, FABP3 and CAV1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that apical NEFA reduced relative TER increase (46.85%) during treatment and increased FITC-albumin flux (27.59%) compared to other treatments. In basal NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased respectively 56.0 and 33.5% of initial FA concentrations. Apical NEFA allowed no FA transfer, but induced LD accumulation and upregulated FA transporter expression (↑CD36, ↑FABP3 and ↑CAV1). Gene expression in apical NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA) and FA uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function-specific gene expression (OVGP1, ESR1 and FOXJ1). Overall, elevated NEFAs affected BOEC metabolism and barrier function differently depending on NEFA exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.


COVID-19 and Total Laryngectomy-A Report of Two Cases.
To date, no cases have been reported on the effects of COVID-19 in laryngectomees. We herein presented two clinical cases of laryngectomized patients affected by COVID-19, detailing their clinical course and complications. In our experience, permanent tracheostomy did not significantly affect the choice of treatment. However, dedicated devices and repeated tracheal toilettes may be needed to deal with oxygen-therapy-related tracheal crusting. In conclusion, laryngectomees should be considered a vulnerable population that may be at risk for worse outcomes of COVID-19 due to anatomical changes in their airways. The role of the ENT specialist is to guide airway management and inform the support-staff regarding specific needs of these patients.


Early Results of Novel Bovine Pericardial Patch Using Comprehensive Anticalcification Procedure in a Swine Model.
We evaluated the short-term safety and effectiveness of our comprehensive anticalcification procedure in swine model. Our comprehensive anticalcification procedure consisted of four steps, including decellularization with sodium dodecyl sulfate and tritonX-100, space filler treatment with polyethylene glycol (PEG), glutaraldehyde cross-linking with organic solvent, and detoxification with glycine. We simultaneously implanted both the commercially available bovine pericardial patch (Supple Peri-Guard) and novel bovine pericardial patch processed by the comprehensive anticalcification procedure into the main pulmonary artery in seven pigs. Every pig underwent a cardiac angiography and was killed on the postoperative day 28. The extracted patches were stained with hematoxylin and eosin. All pigs survived for 4 weeks without any complication. Cardiac angiography showed the absence of leakage and structural problem. Neointimas were formed evenly without intimal hyperplasia. There were no significant differences in the degree of inflammation, necrosis, and calcification between the novel and commercially available patch (p = 0.450, p = 0.317, p = 0.999). Novel bovine pericardial patch using comprehensive anticalcification procedure was similar to existing cardiovascular patch in early surgical results in a swine model. The comprehensive anticalcification procedure could facilitate appropriate bioprosthetic properties of the bovine pericardium.


Gated cardiac tomographic visualization of coronary artery calcification.
Coronary artery calcification (CAC) is usually detected by fluoroscopy or on cine films during coronary angiography, but measurement of the calcification is not possible. Gated tomography of the heart provides a full sized image with high contrast spatial resolution of 0.1 mm and low contrast spatial resolution of 0.76 mm. The radiation exposure to the heart is between 1-5% of that experienced with coronary cinefluorography . Measurement of the diameter of calcium deposits is possible and calcium that could be related to arterial stenosis may be identified.


Choice of Renal Function Estimator Influences Adverse Outcomes with Dabigatran Etexilate in Patients with Atrial Fibrillation.
Background Clinical significance of dosing dabigatran with different estimates of renal function for treatment of atrial fibrillation (AF) is unknown. Renal function is routinely estimated by the chronic kidney disease epidemiology initiative equation (CKD-EPI) and used to guide dosing. The aim of this study was to investigate the risk of adverse outcomes for patients with AF when different estimators of renal function are used. Material and Methods AF patient data were extracted from national administrative databases. Renal function was estimated using Cockcroft-Gault, CKD-EPI, and CKD-EPI adjusted for body surface area (CKD-EPI-BSA). Outcomes of cerebrovascular accident (CVA), systemic embolism (SE), and hemorrhage were extracted. Results In total, 2,425 patients were identified, of which there were hospitalizations for 138 (5.7%) hemorrhagic events, 45 (1.9%) CVA/SE, and 33 (1.4%) unspecified CVA. The level of agreement between Cockcroft-Gault with CKD-EPI and CKD-EPI-BSA yielded a weighted kappa statistic of 0.47 and 0.71, respectively. CKD-EPI and CKD-EPI-BSA significantly overestimated renal function in elderly patients resulting in higher recommended doses compared with Cockcroft-Gault. The hazard ratio for a hemorrhagic event was 2.32 (95% confidence interval, 1.22-4.42; p = 0.01) when a high dose was given compared with normal dose, based on Cockcroft-Gault. Conclusion Both CKD-EPI and CKD-EPI-BSA equations significantly overestimated renal function in the elderly population compared with the Cockcroft-Gault equation. This may lead to dose selection errors for dabigatran, particularly for those with severe impairment, increasing the risk of adverse outcome. Hence, CKD-EPI and CKD-EPI-BSA equations should not be substituted for the Cockcroft-Gault equation in the elderly for the purpose of renal dosage adjustments.


A novel class of antihyperlipidemic agents with low density lipoprotein receptor up-regulation via the adaptor protein autosomal recessive hypercholesterolemia.
We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up-regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC(25) = 0.047 microM). Compound 39 showed no ACAT inhibitory activity even at 1 microM. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression.


Global, quantitative and dynamic mapping of protein subcellular localization.
Subcellular localization critically influences protein function, and cells control protein localization to regulate biological processes. We have developed and applied Dynamic Organellar Maps, a proteomic method that allows global mapping of protein translocation events. We initially used maps statically to generate a database with localization and absolute copy number information for over 8700 proteins from HeLa cells, approaching comprehensive coverage. All major organelles were resolved, with exceptional prediction accuracy (estimated at >92%). Combining spatial and abundance information yielded an unprecedented quantitative view of HeLa cell anatomy and organellar composition, at the protein level. We subsequently demonstrated the dynamic capabilities of the approach by capturing translocation events following EGF stimulation, which we integrated into a quantitative model. Dynamic Organellar Maps enable the proteome-wide analysis of physiological protein movements, without requiring any reagents specific to the investigated process, and will thus be widely applicable in cell biology.


Hemispheric dissociation of the involvement of NOS isoforms in memory for discriminated avoidance in the chick.
Previous research has indicated a role for both the neuronal (nNOS) and endothelial (eNOS) nitric oxide isoforms in memory formation. In addition, two distinct periods of activity of nitric oxide activity, dissociated by hemispheric localization, are implicated following passive avoidance training in the chick. In the present study, we trained black Australorp-white Leghorn chicks on a color discrimination avoidance task. Diphenyleneiodonium chloride (1 microM) or N-propyl-l-arginine (50 microM) was administered into either the left or right hemisphere of the chick brain in an attempt to differentiate the effects of inhibiting eNOS or nNOS, respectively. The memory loss previously observed following administration of diphenyleneiodonium chloride between 10 and 20 min posttraining was found to be lateralized to the right hemisphere, although administration of this agent into the left hemisphere around the time of training was also amnestic. In contrast, N-propyl-l-arginine caused memory loss only when administered to the left hemisphere around the time of training. These findings suggest that activation of both eNOS and nNOS isoforms may be essential for long-term memory consolidation of this task. Further, these two periods of activity are defined temporally and by hemisphere localization, although confirmation with more selective inhibitors when they become available is advised.


Newly established murine pituitary folliculo-stellate-like cell line (TtT/GF) secretes potent pituitary glandular cell survival factors, one of which corresponds to metalloproteinase inhibitor.
A mouse folliculo-stellate cell (FS cell) line, TtT/GF, was found to secrete a potent survival factor influencing a somatotropic cell line (MtT/S) in serum-free medium. A three-step chromatography purification procedure using heparin-affinity chromatography, anion-exchange chromatography and gel-filtration chromatography revealed that the factor was a 27 kDa protein. Amino-terminal sequence analysis showed that the N-terminal 20 amino acids of the 27 kDa protein corresponded to those of human tissue inhibitor of metalloproteinase-II (TIMP-II). These results indicate that FS cells secrete TIMP-II, which probably protects the composition of the extracellular matrix and acts as a cell survival factor for endocrine cells in the anterior pituitary gland.


Extracellular Matrix and Integrin Expression Profiles in Fuchs Endothelial Corneal Dystrophy Cells and Tissue Model.
Primary corneal endothelial cell (CEC) cultures and 3D-engineered tissue models were used to study the aberrant deposition of extracellular matrix (ECM) in a vision impairing pathology known as Fuchs endothelial corneal dystrophy (FECD). CECs were isolated from excised Descemet membranes of patients with end-stage FECD. CECs isolated from healthy corneas served as controls. Microarray gene profiling was performed on postconfluent cultures of healthy and FECD cells. Protein expression analyses were conducted on tissue models that were engineered by seeding an endothelium on previously devitalized human stromal carriers. The engineered endothelia were kept in culture for 1-3 weeks to reform the endothelial monolayer. Protein expression of integrin subunits α4, α6, αv, and β1, as well as laminin, type IV collagen, fibronectin, clusterin, and transforming growth factor β-induced protein (TGFβIp) was then assessed by immunofluorescence. Microarray analysis showed nonstatistical twofold downregulation of collagen-coding genes (COL4A4, COL8A2, and COL21A1) and a twofold upregulation of the COL6A1, laminin α3 gene LAMA3, and integrin subunit α10 gene ITGA10 in FECD cells. Fibronectin type III domain containing 4 (FNDC4) and integrin β5 (ITGB5) genes was significantly upregulated in FECD cells. Immunostainings demonstrated that the protein expression of the integrin subunits α4, α6, αv, and β1, type IV collagen, as well as laminin remained similar between native and engineered endothelia. TGFβIp expression was found on the stromal side of both FECD and healthy Descemet's membrane, and only one out of three FECD specimens was positive for the clusterin protein. Interestingly, the ECM protein fibronectin was also found to have a stronger presence on engineered FECD tissues, a result consistent with the native FECD specimens. To conclude, this study allowed to identify fibronectin deposition as one of the first steps in the pathogenesis of FECD, as defined by our engineered tissue model. This opens the way to an entirely new perspective for in vitro pharmacological testing of new therapies for FECD, the leading indication for corneal transplantation in North America.


Metal concentration and health risk assessment of wild mushrooms collected from the Black Sea region of Turkey.
Mushrooms are rich sources of organic nutrients (especially proteins). However, they can excessively accumulate metals in their fruiting bodies that pose a risk to human health. The aim of this study was the determination of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn contents, daily intake, and health risk index values of some mushroom species collected from the eastern Black Sea region of Turkey (Arsin, Trabzon). The samples were collected from hazelnut gardens that are free from industrial pollution and have a low population density. As a result of elemental analysis, it was determined that the concentration ranges of Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn in the mushrooms were as follows: 0.29-9.11, 0.04-3.70, 0.01-8.29, 0.18-20.82, 3.1-79.8, 5.2-673.0, 14.9-752.0, 63.0-7769.0 mg/kg dry weight. Daily intakes of all the elements were found to be below the reference dose in Fistulina hepatica, Hydnum repandum, Macrolepiota procera, and Tapinella atrotomentosa. Amanita caesarea, Agrocybe praecox, Amanita vaginata, Cantharellus cibarius, Craterellus cornucopioides, Daedalea quercina, Gymnopus dryophilus, Ganoderma lucidum, and Infundibulicybe gibba were found to have high risk index values especially with respect to Cd, Co, and Pb. According to Pearson correlation analysis, the correlations between Fe-Mn (0.840, p < 0.01) and Pb-Ni (0.7540, p < 0.01) couples are significant.


Flavonoids with potent antioxidant activity found in young green barley leaves.
Saponarin, a flavonoid found in young green barley leaves, possesses potent antioxidant activities, which are determined by its inhibition of malonaldehyde (MA) formation from various lipids oxidized by UV light or Fenton's reagent. Lipids used were squalene, ethyl linoleate, ethyl linolenate, ethyl arachidonate, octadecatetraenoic acid (ODTA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), cod liver oil, lecithin I, lecithin II, and blood plasma. The addition of saponarin inhibited the formation of MA from squalene upon UV irradiation at the level of 2 μmol/mL by almost 100%, whereas BHT inhibited its formation by 75% at the same level. Saponarin showed potent antioxidant activity toward fatty acid ethyl esters at levels >100 μg/mL. Saponarin inhibited MA formation in ODTA by 60%, in EPA by 50%, and in DHA by 43% at the level of 15 μmol/mL. Saponarin exhibited strong antioxidant activities with dose-response levels toward cod liver oil and lipoproteins (lecithins I and II), higher than those of α-tocopherol. A mixture of saponarin/lutonarin (4.5:1, w/w) inhibited MA formation appreciably from all lipids tested with dose response. This mixture exhibited highest effect toward cod liver oil (86%), followed by DHA, lecithin II, blood plasma, EPA, and lecithin I. Supplementation of young green barley leaves containing saponarin should be beneficial to health and may prevent diseases caused by oxidative damage such as various cancers, inflammations, and cardiovascular diseases.


The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.
Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom. It is a potent activator of platelets, resulting in a collagen-like response by binding and clustering platelet receptor CLEC-2. We present here the crystal structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary structure. The two alphabeta heterodimers are arranged through 2-fold rotational symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus presents two ligand binding sites on one surface and can therefore cluster ligands in a manner reminiscent of convulxin and flavocetin. To examine the molecular basis of the interaction with CLEC-2, we used a molecular modeling approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal domain (CLEC-2N). This model positions the CLEC-2N structure face down in the "saddle"-shaped binding site which lies between the aggretin alpha and beta lectin-like domains. A 2-fold rotation of this complex to generate the aggretin tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini into the proximity of each other, and a series of contacts involving two interlocking beta-strands close to the N-terminus are described. A comparison with homologous lectin-like domains from the immunoreceptor family reveals a similar but not identical dimerization mode, suggesting this structure may represent the clustered form of CLEC-2 capable of signaling across the platelet membrane.


Cadmium--influence on biochemical processes of the human organism.
Heavy metals are too well-known environmental pollutants of particularly dangerous effect to human health. Because of their wide usage in many industrial branches they are present everywhere in the air, water and soils. Food contamination by heavy elements is hard to avoid and it is a result of environmental contamination by dusts, industrial gases, sewage, waste and coal burning processes. One of the most harmful heavy metals, widely spread in nature is cadmium. Toxic cadmium action involves free oxygen generation and inactivation of protein containing cysteine residues with -SH groups. It influences many metabolic processes causing great damage in many organs. Cadmium can also interact with some essential elements leading to their homeostasis disorders.


Vector magnetic field sensor based on U-bent single-mode fiber and magnetic fluid.
A novel, compact, and easy fabrication vector magnetic field sensor has been proposed and investigated. The proposed sensor consists of a U-bent single-mode fiber fixed in a magnetic-fluid-filled vessel. Neither mechanical modification nor additional fiber grating is needed during the sensor fabrication. The results show that the response of magnetic fluid to magnetic field can be used to measure the direction and intensity of magnetic field via whispering gallery modes supported by the U-bent fiber structure with suitable bending radius. The sensitivity of direction is 0.251 nm/°, and the maximum magnetic field intensity sensitivity is 0.517 nm/mT. Besides, the results of this work prove the feasibility for realizing vector magnetic sensors based on other bending structures (such as bending multimode interference, bending SPR structure) in the future.


Augmentation of Antipsychotic Medications with Low-Dose Clozapine in Treatment-Resistant Schizophrenia-Case Reports and Discussion.
Treatment resistance in schizophrenia is often encountered in clinical practice, with clozapine usually recommended as the appropriate therapy. However, where clozapine proves ineffective or cannot be tolerated due to side effects, treatment options are limited. In patients within forensic mental health services, residual symptomatology often presents a barrier to discharge and can have lasting effects on prospects for rehabilitation as well as risk to self and others. This paper presents a review of the relevant literature and three cases of a novel approach, utilising clozapine in doses usually considered subtherapeutic, in combination with the primary antipsychotic treatment. In all three patients, it improved clinical efficacy as well as tolerability, resulting in improvement that allowed discharge from the forensic hospital.


Thoracolumbar fracture management: anterior approach.
The surgeon who treats patients with spine trauma must be able to apply a variety of management techniques to achieve optimal care of the patient. The anterior surgical approach is appropriate for some thoracolumbar burst fractures in patients with neurologic deficit and without posterior ligamentous injury. Surgery is most often indicated for patients with incomplete deficit, especially those with a large retropulsed fragment, marked canal compromise, severe anterior comminution, or kyphosis <30 degrees. This approach provides excellent visualization of the anterior aspect of the dura mater for decompression. Reconstruction of the anterior body defect can be done with autograft, allograft, or a cage. Supplementation of the graft with anterior internal fixation helps prevent kyphosis. Clinical results demonstrate improved neurologic function in most patients as well as low pseudarthrosis rates. In patients with incomplete deficit, improvement in neurologic function usually can be expected with few complications.


Surveying physical therapists' understanding of benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo (BPPV) is a common condition with disabling symptoms that is diagnosed and effectively treated at the bedside. Our encounter with patients experiencing prolonged BPPV who may not have received appropriate physical therapy prompted us to explore barriers to the diagnosis and treatment for BPPV among physical therapists, which has not been extensively investigated. We hypothesize that a potential barrier may be a lack of understanding of subtle symptoms of BPPV that deviate from the classical presentation. The gold standard for diagnosing definite BPPV is subjective dizziness or vertigo with nystagmus in response to positional testing. There are variants of BPPV including subjective BPPV (subjective dizziness or vertigo without nystagmus) and vestibular agnosia (nystagmus without subjective dizziness or vertigo) that do not meet the diagnostic criteria for definite BPPV but are equally responsive to the same repositioning maneuvers. The purpose of this project was to survey physical therapists for their understanding of BPPV including subjective BPPV and vestibular agnosia. A panel of experts created a 16-question survey, designed for physical therapists, with three categories: (1), inquiring if they treat persons with BPPV, (2) three clinical vignettes for definite BPPV, subjective BPPV, and BPPV with vestibular agnosia, and (3) demographic information. Data collection occurred at two large physical therapy meetings, one of which was a national professional meeting and the other was a professional continuing medical education course geared towards advancing vestibular rehabilitation skills. There were 426 people who completed the survey, 364 of whom treat BPPV in their practice. In the first clinical vignette created to assess the respondents' understanding of definite BPPV, 229 (62%) of respondents would always assess a patient for BPPV based on complaints of a "room spinning" vertigo from head movement. When asked if the complaint was lingering "lightheadedness or feelings of imbalance" from head movement, only 158 (43%) reported they would perform positional testing to reassess. In the BPPV variant vignettes, 187 (51%) identified the patient with subjective BPPV as having BPPV and 305 (85%) identified the patient with vestibular agnosia as having BPPV. The results of this survey demonstrate gaps in knowledge regarding BPPV across practice settings and experience, with opportunities to bridge these gaps to improve treatment for BPPV.


High throughput system for magnetic manipulation of cells, polymers, and biomaterials.
In the past decade, high throughput screening (HTS) has changed the way biochemical assays are performed, but manipulation and mechanical measurement of micro- and nanoscale systems have not benefited from this trend. Techniques using microbeads (particles approximately 0.1-10 mum) show promise for enabling high throughput mechanical measurements of microscopic systems. We demonstrate instrumentation to magnetically drive microbeads in a biocompatible, multiwell magnetic force system. It is based on commercial HTS standards and is scalable to 96 wells. Cells can be cultured in this magnetic high throughput system (MHTS). The MHTS can apply independently controlled forces to 16 specimen wells. Force calibrations demonstrate forces in excess of 1 nN, predicted force saturation as a function of pole material, and powerlaw dependence of F approximately r(-2.7+/-0.1). We employ this system to measure the stiffness of SR2+ Drosophila cells. MHTS technology is a key step toward a high throughput screening system for micro- and nanoscale biophysical experiments.


oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading.
Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu2+-oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu2+-oxLDL enhanced HAECs' proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu2+-oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27kip1). Both Cu2+-oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu2+- and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27kip1 Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis.


Characterization of neuroinflammation pattern in anti-LGI1 encephalitis based on TSPO PET and symptom clustering analysis.
TSPO PET with radioligand [18F]DPA-714 is an emerging molecular imaging technique that reflects cerebral inflammation and microglial activation, and it has been recently used in central nervous system diseases. In this study, we aimed to investigate the neuroinflammation pattern of anti-leucine-rich glioma-inactivated 1 (LGI1) protein autoimmune encephalitis (AIE) and to evaluate its possible correlation with clinical phenotypes. Twenty patients with anti-LGI1 encephalitis from the autoimmune encephalitis cohort in Huashan Hospital and ten with other AIE and non-inflammatory diseases that underwent TSPO PET imaging were included in the current study. Increased regional [18F]DPA-714 retention in anti-LGI1 encephalitis was detected on a voxel basis using statistic parametric mapping analysis. Multiple correspondence analysis and hierarchical clustering were conducted for discriminate subgroups in anti-LGI1 encephalitis. Standardized uptake value ratios normalized to the cerebellum (SUVRc) were calculated for semiquantitative analysis of TSPO PET features between different LGI1-AIE subgroups. Increased regional retention of [18F]DPA-714 was identified in the bilateral hippocampus, caudate nucleus, and frontal cortex in LGI1-AIE patients. Two subgroups of LGI1-AIE patients were distinguished based on the top seven common symptoms. Patients in cluster 1 had a high frequency of facio-brachial dystonic seizures than those in cluster 2 (p = 0.004), whereas patients in cluster 2 had a higher frequency of general tonic-clonic (GTC) seizures than those in cluster 1 (p < 0.001). Supplementary motor area and superior frontal gyrus showed higher [18F]DPA-714 retention in cluster 2 patients compared with those in cluster 1 (p = 0.024; p = 0.04, respectively). Anti-LGI1 encephalitis had a distinctive molecular imaging pattern presented by TSPO PET scan. LGI1-AIE patients with higher retention of [18F]DPA-714 in the frontal cortex were more prone to present with GTC seizures. Further studies are required for verifying its value in clinical application.


18-F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Rare Case of Post-COVID-19 Mucormycosis of Femur.
COVID-19 disease was spread rapidly on a global scale. Corticosteroids were believed to reduce the inflammatory lung injury, however, its side effects include increased secondary infections, immunomodulation, and manifestation of latent diabetes mellitus. The incidence of mucormycosis infection was high in post COVID-19-infected patients. Mucormycosis of femur in patients of post-COVID-19 infection was extremely rare and not yet reported. We report a case of COVID-19 recovered patient with mucormycosis of right distal femur, who underwent 18Ffluorodeoxyglucose (18FFDG) positron emission tomography/computed tomography (PET/CT) for additional sites of disease. This case highlights potential of 18FFDG PET/CT in the management of mucormycosis.


Capping layer enabled controlled fragmentation of two-dimensional materials by cold drawing.
Cold drawing, a well-established processing technique in the polymer industry, was recently revisited and discovered as an efficient material structuring method to create ordered patterns in composites consisting of both cold-drawable polymers and brittle target materials. Such a high-yield and low-cost manufacturing technique enables the large-scale fabrication of micro-ribbon structures for a wide range of functional materials, including two-dimensional (2D) layered materials. Compared to the abundant phenomenological results from experiments, however, the underlying mechanisms of this technique are not fully explored. Here, supported by experimental investigation, finite element calculations, and theoretical modeling, we systematically study the effect of a capping layer on the controlled fragmentation of 2D materials deposited on polymer substrates during the cold drawing. The capping layer is found to prevent the premature fracture of the 2D thin films during elastic deformation of the substrate, when a specific requirement proposed by the theoretical model is satisfied. Controlled fragmentation is enabled in the necking stage due to the protective effect of the capping layer, which also influences the size of the resulting fragments. Flexible and stretchable electrodes based on 2D material ribbons are fabricated to demonstrate the effectiveness of the proposed roadmap. This study gives an accurate understanding of interactions between 2D materials, polymer substrates, and capping layers during cold drawing, and offers guidance for potential applications such as flexible electronics.


Mood and symptom reporting among middle-aged women: the relationship between menopausal status, hormone replacement therapy, and exercise participation.
Vasomotor, somatic, and psychological symptoms associated with menopause are often treated with hormone replacement therapy (HRT), but the role of nonpharmacological interventions has received little attention. Two studies used the Profile of Mood States (POMS) and Women's Health Questionnaire (WHQ) to examine the effects of exercise among 4 groups of Australian women: premenopausal, perimenopausal, postmenopausal without HRT, and postmenopausal with HRT. Study 1, a comparison of exercisers and nonexercisers, showed that exercisers' moods were significantly more positive than sedentary women's moods, regardless of menopausal state. Exercising women also scored lower on somatic symptoms and memory-concentration difficulties. Study 2 examined the acute effects of aerobic exercise (premenopausal, postmenopausal without HRT, and postmenopausal with HRT) and found significant enhancements in mood and reductions in reported somatic and vasomotor symptoms immediately following an aerobic class. Exercise may assist in the alleviation of some menopausal symptoms.


Late embryo mortality in Holstein cows inseminated with Holstein or Limousine frozen semen.
The objective of this study was to compare the late embryo mortality (LEM) rate (losses approximately between 32 and 53 days of gestation) and Pregnancy Specific Protein B (PSPB) and progesterone (P4) concentrations on day 32 post AI in Holstein cows bred with either Holstein or Limousine semen. A sample size of 1082 cows per group diagnosed pregnant between 28- and 35-days post breeding was calculated. The study consisted of evaluating LEM (%) in a cohort of Holstein cows bred with Holstein semen (HO × HO) or Limousine semen (HO × LM), to compare pregnancy loss from 28 to 35 days post breeding to 50-57 days post breeding. A logistic regression model to compare embryo losses was developed considering as main explanatory variable the cohort (HO × HO embryo vs. HO × LM embryo), correcting by lactation number, breeding season, days to breeding and AI technician. HO × HO embryos had greater LEM (15.16%) than HO × LM embryos (9.79%). Cows bred in summertime had higher LEM (15.23%) than cows bred in no-summertime (9.88%). There were no differences among AI technicians. Within summertime there was no difference in LEM (%) between groups within each lactation number; yet, within no-summertime, LEM (%) was higher in HO × HO than HO × LM within each lactation number. Pregnancy SPB optical densities were significantly greater in the HO × HO than in the HO × LM (p = .023) group; yet, the concentration of P4 was not different between groups (p > .05).


Clinicopathological Characteristics and Prognosis of Papillary Thyroid Carcinoma in Naturally Menopausal Women with Various Durations of Premenarche, Reproductive Periods, and Postmenopausal Stages.
Background. Papillary thyroid cancer (PTC) exhibits a higher incidence in women. Due to various ages at menarche and menopause, estrogen levels vary, which may account for the differences in the occurrence, development, and prognosis of female patients with PTC. Objective. The aim of this study was to investigate the association between various durations in different estrogen levels and PTC and to provide important information to guide clinical management and treatment of this disease. Methods. First, we selected naturally menopausal female study subjects diagnosed with PTC at Zhejiang Cancer Hospital from 2007 to 2012 and then compared the differences in clinicopathological characteristics and prognosis among subjects with various lengths of premenarche, reproductive periods, and postmenopausal stages. Results. We found that all patients showed a significantly higher incidence of tumor multicentricity and intrathyroidal dissemination as the time after menopause increased. Additionally, women with shorter (<30) or longer (>38) reproductive lives had increased recurrence rates of PTC. Conclusions. In this study, we did not find any relationship of self-reported menarche and menopausal ages with the prognosis of PTC patients. More importantly, natural postmenopausal PTC patients with shorter or longer reproductive life, compared to the normal groups, had a higher rate of cancer recurrence and the patients with these characteristics could be recommended a more aggressive surgical treatment.


The Importance of Patellar Resurfacing in Total Knee Arthroplasty for Symptomatic Valgus Degenerative Deformity.
PURPOSE OF THE STUDY Patellar surface replacement during total knee arthroplasty is still a matter of discussion among orthopedic surgeons. The purpose of this study was to examine possible benefits of patellar surface replacement in selected patients with symptomatic degenerative valgus deformity. We have not found any studies in the literature that compare the results of patella management solely for valgus or varus knee deformity nor those that compare both. MATERIAL AND METHODS Patients were randomly assigned to a group that would receive patellar surface replacement during total knee arthroplasty and a group of patients in whom total knee arthroplasty was performed without patellar surface replacement. 60 patients were included in the study. Total knee arthroplasty with patellar resurfacing (TKAPR) was performed in 30, and without PR (TKA) in 30 of them. Results were prospectively gathered and compared at regular intervals. RESULTS There were no significant differences between groups for examined parameters except for Oxford Knee Score at 6 months which was in favor of patellar resurfacing group. DISCUSSION The decision whether to replace the patella or not is currently exclusively a matter of surgeon's choice. Establishing selection criteria for patients that would benefit from patella resurfacing could, therefore, be very useful for both patients and orthopaedic surgeons performing total knee replacement. CONCLUSIONS Although evidence in our study could not strongly suggest performing patella resurfacing in patients with valgus deformity, the results were slightly better in the patella resurfacing group and this trend could increase if larger series of patients would be employed. A longer follow-up period would be required for clear-cut decisions and more prospective studies are warranted. Key words: knee, arthroplasty, patella, replacement, valgus, deformity.


Combined in utero and juvenile exposure of mice to arsenate and atrazine in drinking water modulates gene expression and clonogenicity of myeloid progenitors.
The effects of arsenate (As) and atrazine (Atr) on myeloid progenitors (colony-forming unit-granulocyte/macrophage, CFU-GM) cells derived from bone marrow were studied in male and female mice after combined in utero and juvenile exposure. Female adult mice were treated with arsenate in drinking water during gestation. Then, separate groups of males and females' offspring were exposed for 4 months to atrazine, to additional arsenate or to co-exposure of atrazine and arsenate together in drinking water. In male mice, arsenate and the combined exposure did not modulate the percentage of CFU-GM progenitors, whereas atrazine significantly decreases the clonogenicity of myeloid cells. In females, the percentage of CFU-GM significantly decreased after atrazine exposure did not change with arsenate treatment, but dramatically increased after the combined exposure. The expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in bone marrow cells was investigated, and an up-regulation of receptor beta was observed in both genders. A gene expression profile was generated using nylon membranes spotted with 1185 cancer-related genes. Results from microarrays indicate that atrazine alone did not stimulate the expression of any of the genes analysed in both male and female. Arsenic induced gene expression modulation only in female. Major significant changes on the gene expression resulted following the co-exposure to arsenic and atrazine in both male and female.


Sister Chromatid Exchanges in A Male With A Y/Y Translocation.
Sister chromatid exchanges (SCE) are considered indicators of genetic damage and early chromosome changes. The SCE frequency from an infertile 27-year-old, white male with tall stature and a nondicentric Y/Y translocation consisting of one short arm and two long arms of the Y chromosome was determined. The SCE frequency was 7.9 ± SD 1.4 while the SCE frequency from ten control subjects was 8.4 ± SD 0.51. A two-tailed t-test was applied to the SCE data and no significant difference was found between the individual with the Y/Y translocation and control subjects. Apparently, this altered chromosome does not interfere with the total chromosome behavior and the number of SCEs produced when compared to ten control subjects of both sexes.


Salubrinal alleviates cartilage degradation in a rabbit temporomandibular joint osteoarthritis model.
To investigate and explain the beneficial effects of local intra-articular injection of Salubrinal on temporomandibular joint osteoarthritis (TMJOA) using a rabbit model of anterior disc displacement (ADD). Rabbits were divided and subjected to surgical ADD. Salubrinal was administered by intra-articular injection in the TMJ every other day for 2 and 4 weeks after operation. Histological examination and TUNEL staining were then performed. Immunohistochemistry, quantitative real-time PCR, and Western blot analysis were employed to evaluate the expression of endoplasmic reticulum (ER) stress-related markers, catabolic factors, extracellular matrix proteins, inflammatory factors, and nuclear factor-kappa B (NF-κB) activation. In the ADD groups, we found that Salubrinal partly reversed condylar cartilage deterioration according to the histological analysis. Salubrinal reduced chondrocytes apoptosis while increased matrix components including Collagen II and Aggrecan. Meanwhile, Salubrinal downregulated the catabolic expression of MMP13, ADAMTS5, VEGF, TNF-α, and IL-1β. We also observed that Salubrinal inhibited ER stress activation by reducing the expression of GRP78, CHOP, ATF4, and Caspase-12. Additionally, Salubrinal suppressed the phosphorylation of NF-κB. These results indicate that Salubrinal alleviates cartilage degradation following ADD, suggesting that intra-articular injection of Salubrinal is a potential therapeutic approach for preventing TMJOA.


Degradable Semiconducting Oligomer Amphiphile for Ratiometric Photoacoustic Imaging of Hypochlorite.
Upregulation of highly reactive oxygen species (ROS) such as hypochlorite (ClO-) is associated with many pathological conditions including cardiovascular diseases, neuron degeneration, lung injury, and cancer. However, real-time imaging of ClO- is limited to the probes generally relying on fluorescence with shallow tissue-penetration depth. We here propose a self-assembly approach to develop activatable and degradable photoacoustic (PA) nanoprobes for in vivo imaging of ClO-. A near-infrared absorbing amphiphilic oligomer is synthesized to undergo degradation in the presence of a specific ROS (ClO-), which integrates a π-conjugated but ClO- oxidizable backbone with hydrophilic PEG side chains. This molecular architecture allows the oligomer to serve as a degradable nanocarrier to encapsulate the ROS-inert dye and self-assemble into structurally stable nanoparticles through both π-π stacking and hydrophobic interactions. The self-assembled nanoprobe exhibits sensitive and specific ratiometric PA signals toward ClO-, permitting ratiometric PA imaging of ClO- in the tumor of living mice.


Dual microcatheter coil embolization of acutely ruptured wide-necked intracranial aneurysms.
The dual microcatheter technique is an alternative treatment for stent-assisted coiling in acutely ruptured wide-necked aneurysms because of no antiplatelet therapy. We assessed the safety and efficacy of this technique in ruptured wide-necked aneurysms. Between March 2008 and March 2016, 56 acutely ruptured aneurysms were treated with the dual microcatheter technique. The angiographic results, treatment-related complications, and clinical outcome were documented. Angiographic follow-up was available in 37 patients at a mean of 20.6 months (6 to 81 months). On the postembolization angiograms, 27 (48.2%) aneurysms showed complete occlusion (Raymond 1), 15 (26.8%) showed neck remnant (Raymond 2), and 14 (25.0%) showed body remnant (Raymond 3). Treatment-related complications occurred in seven patients (12.5%) and six patients remained asymptomatic. The permanent complication rate was 1.8% (1/56). A good outcome (modified Rankin Scale (mRS) score, 0-2) was observed in 64.3% of patients at the time of discharge. Five patients had died, all of the sequelae of subarachnoid hemorrhage. The overall mortality rate was 8.9% (5/56); however, the treatment-related mortality rate was 0%. Of the 37 aneurysms for which angiographic follow-up was available, 21 (56.8%) aneurysms demonstrated recanalization. Five aneurysms with recanalization were retreated endovascularly. There was one aneurysm re-rupture on follow-up and it rebled 21 months after the initial procedure. The dual microcatheter technique is a safe and effective treatment for acutely ruptured wide-necked aneurysms due to low treatment-related complication and mortality rate. However, the high rate of postembolization incomplete occlusion and recanalization remains as the main challenge.


Preparation and characterization of regenerated cellulose from ionic liquid using different methods.
In this study, regenerated cellulose was prepared from ionic liquid 1-butyl-3-methylimidazolium acetate ([Bmim]Ac) solution using anti-solvent compressed CO2 of different pressures. And other anti-solvents like water, ethanol and acetonitrile were also employed to regenerate cellulose to provide comparisons. The two-dimensional nuclear magnetic resonance (2D NMR), namely heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond coherence (HMBC), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) indicated that carboxylate zwitterions [Bmim(+)-COO(-)] formed through the chemical reactions between CO2 and [Bmim]Ac. Besides, FTIR, wide-angle X-ray diffraction (XRD), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to provided structure characterization of native and regenerated cellulose using different anti-solvents. The results show that the crystallinity of cellulose decreases during the dissolution and regeneration process. And a crystal transformation of cellulose I to cellulose II was verified. The stability of the regenerated cellulose is lower than that of native cellulose. A higher compressed CO2 pressure results in a smoother surface, a thicker shape and a more homogeneous texture of regenerated cellulose.


Folding stability and cooperativity of the three forms of 1-110 residues fragment of staphylococcal nuclease.
Folding stability and cooperativity of the three forms of 1-110 residues fragment of staphylococcal nuclease (SNase110) have been studied by various biophysical and NMR methods. Samples of G-88W- and V-66W-mutant SNase110, namely G-88W110 and V-66W110, in aqueous solution and SNase110 in 2.0 M TMAO are adopted in this study. The unfolding transitions and folded conformations of the three SNase fragments were detected by far- and near-ultraviolet circular dichroism and intrinsic tryptophan fluorescence measurements. The tertiary structures and internal motions of the fragments were determined by NMR spectroscopy. Both G-88W and V-66W single mutations as well as a small organic osmolyte (Trimethylamine N-oxide, TMAO) can fold the fragment into a native-like conformation. However, the tertiary structures of the three fragments exhibit different degrees of folding stability and compactness. G-88W110 adopts a relatively rigid structure representing a most stable native-like beta-subdomain conformation of the three fragments. V-66W110- and TMAO-stabilized SNase110 produce less compact structures having a less stable "beta-barrel" structural region. The different folding status accounts for the different backbone dynamic and urea-unfolding transition features of the three fragments. The G-20I/G-29I-mutant variants of the three fragments have provided the evidence that the folding status is correlated closely to the packing of the beta-strands in the beta-barrel of the fragments. The native-like beta-barrel structural region acts as a nonlocal nucleus for folding the fragment. The tertiary folding of the three fragments is initiated by formation of the local nucleation sites at two beta-turn regions, I-18-D-21 and Y-27-Q-30, and developed by the formation of a nonlocal nucleation site at the beta-barrel region. The formation of beta-barrel and overall structure is concerted, but the level of cooperativity is different for the three 1-110 residues SNase fragments.


Sorbitol dehydrogenase expression is regulated by androgens in the human prostate.
Sorbitol is an intermediate in the polyol pathway, which converts from glucose to fructose by sorbitol dehydrogenase (SORD). Androgens are essential for the development of prostate cancer. We studied castration-induced gene expression changes in the human prostate using the GeneChip array, and identified SORD as being androgen-regulated in the human prostate. A putative androgen-responsive regulatory region at the SORD 5' promoter was identified using promoter deletion constructs in a luciferase reporter assay in COS-7 cells. Chromatin immunoprecipitation assay was used to assess the binding of androgen receptor to suggested androgen responsive regulatory region. Finally, the expression of SORD in the human prostate was evaluated in 29 prostate tissue samples by immunohistochemistry. The expression of SORD decreased after castration. Androgen supplementation to the LNCaP prostate cancer cell line led to a 7.5-fold increase in SORD mRNA expression. Furthermore, a chromatin immunoprecipitation assay proved that the androgen receptor can bind to this putative androgen-responsive regulatory region. Finally, the expression of SORD in the human prostate was localised to epithelial cells of both benign and malignant prostate tissue by immunohistochemistry. In prostate cancer, increased immunostaining was associated with high Gleason patterns and high serum prostate-specific antigen concentrations. These results show that SORD is a novel androgen-regulated gene in the human prostate and suggest the need for more detailed analysis of the physiological role of SORD in the prostate.


Blood thixotropy in patients with sickle cell anaemia: role of haematocrit and red blood cell rheological properties.
We compared the blood thixotropic/shear-thinning properties and the red blood cells' (RBC) rheological properties between a group of patients with sickle cell anaemia (SS) and healthy individuals (AA). Blood thixotropy was determined by measuring blood viscosity with a capillary viscometer using a "loop" protocol: the shear rate started at 1 s-1 and increased progressively to 922 s-1 and then re-decreased to the initial shear rate. Measurements were performed at native haematocrit for the two groups and at 25% and 40% haematocrit for the AA and SS individuals, respectively. RBC deformability was determined by ektacytometry and RBC aggregation properties by laser backscatter versus time. AA at native haematocrit had higher blood thixotropic index than SS at native haematocrit and AA at 25% haematocrit. At 40% haematocrit, SS had higher blood thixotropic index than AA. While RBC deformability and aggregation were lower in SS than in AA, the strength of RBC aggregates was higher in the former population. Our results showed that 1) anaemia is the main modulator of blood thixtropy and 2) the low RBC deformability and high RBC aggregates strength cause higher blood thixotropy in SS patients than in AA individuals at 40% haematocrit, which could impact blood flow in certain vascular compartments.


Partnering with youth to map their neighborhood environments: a multilayered GIS approach.
Mapping approaches offer great potential for community-based participatory researchers interested in displaying youth perceptions and advocating for change. We describe a multilayered approach for gaining local knowledge of neighborhood environments that engages youths as coresearchers and active knowledge producers. By integrating geographic information systems with environmental audits, an interactive focus group, and sketch mapping, the approach provides a place-based understanding of physical activity resources from the situated experience of youths. Youths report safety and a lack of recreational resources as inhibiting physical activity. Maps reflecting youth perceptions aid policy makers in making place-based improvements for youth neighborhood environments.


The diagnosis and management of common inherited bleeding disorders.
Inherited bleeding disorders can be associated with significant morbidity and mortality. Bleeding episodes can be safely and effectively managed in the majority of patients provided the coagulation defect is identified and corrected with the appropriate replacement therapy. It is imperative that these patients are treated in centres that can provide full coagulation support, and a comprehensive care plan is formulated for each individual.


Physiological Variation Among Clonal Genotypes in the Sea Anemone Haliplanella lineata: Growth and Biochemical Content.
We have explored physiological variability among clonal genotypes from a single population of the sea anemone Haliplanella lineata located at Indian Field Creek, Virginia. Information about the correlation between physiological variability and genetic differences may provide a foundation for a mechanistic understanding of the breadth of adaptation of individual genotypes (i.e., the nature of "general purpose genotypes") and of the concept of localized adaptation in clonal anemones. Anemones from three clones (A, B, C) were fed measured rations of adult Artemia, after which growth, absorption efficiency, and net growth efficiency were determined. Biochemical constituents were measured in the tissue of this group of anemones as well as in the tissue of anemones from the same clones that had fed ad libitum on Artemia nauplii. Anemones from the different clones did not differ significantly in growth, or gravimetric absorption or growth efficiencies, but significant differences were found in biochemical composition. Regardless of feeding regime and diet composition, clone B anemones consistently had lower tissue averages of triacylglycerols, fatty acids, sterol and wax esters, glycerol ethers, and carbohydrates than did clone A and clone C anemones. As a result of differences in the carbohydrate and lipid constituents, the energetic content of tissues from clone B anemones that had been fed rations was significantly lower than the energetic content of tissues of anemones from clone C. This clonal pattern in biochemical composition and energetic content may be due to differences in substrate absorption among anemones from the different clones, to differences in metabolic rate, or to a combination of both. Because anemones from this population may encyst in mucus and stop feeding when water temperatures are less than 10{deg}C, the genotypic differences in storage lipids and carbohydrate may have implications for the winter survivorship of clone B anemones in this population.


YfilerⓇ Plus population samples and dilution series: stutters, analytic thresholds, and drop-out probabilities.
The Yfiler Ⓡ Plus Amplification Kit amplifies 27 Y chromosomal small tandem repeat (STR) markers. The kit has five-fluorescent dye chemistry and the improved PCR buffer system of modern STR kits. We validated the kit for accredited investigations of crime scene samples by a thorough study of kit dynamics and performance. We determined dye-dependent analytical thresholds by receiver operating characteristics (ROC) and made a customised artefact filter that includes theoretical known artefacts by use of previously analysed population samples. Dilution series of known male DNA and a selection of crime scene samples were analysed with the customised thresholds and artefact filters. The Yfiler Ⓡ Plus Amplification Kit was sensitive giving full profiles down to 70 pg of male DNA. The balances between the fluorescent dyes as well as between loci were very good. The kit was able to produce full Y-STR profiles from crime scene samples containing small amounts of male DNA and large amounts of female DNA (although unspecific reactions were evident for very unbalanced mixtures). A decrease in the drop-out rate was found for both the dilution series and population samples, as well as a small increase in the drop-in rate for population samples, using the customised threshold and artefact filters compared to company-provided thresholds and artefact filters. The additional drop-ins were all of a nature that would be detected by inspection of the results. For the crime scene samples, large amounts of female DNA complicated the analysis by causing drop-ins of characteristic female DNA artefacts. Even though the customised analytical threshold in combination with the custom-made artefact filters gave more alleles, crime scene samples still needed special attention from the forensic geneticist.


Generality of the tRNA origin of short interspersed repetitive elements (SINEs). Characterization of three different tRNA-derived retroposons in the octopus.
Transcription in vitro of total genomic DNA of Octopus vulgaris resulted in PolIII transcripts of 200 to 500 nucleotides in length. These transcripts were used as probes and, as a result, three different kinds of short interspersed element (SINE) were isolated and characterized. Two SINEs, designated the octopus OR1 and OR2 families, seem to have been derived from tRNA(Arg). The other SINE, designated the octopus OK family, have originated from tRNA, but the parental tRNA species cannot be identified due to sequence divergence from the original tRNA sequence. The OR1 and OR2 families exhibit considerable similarity to one another, in the 5' region of the tRNA-unrelated region as well as in the tRNA(Arg)-related region, an observation that suggests that these two families may have had the same origin in evolution. The three SINEs together constitute at least 6% of the genome of O. vulgaris. Results of a dot hybridization experiment suggest that the OR1 and OR2 families are present in fewer species than the OK family and that the OK family exists in many species of octopodid. The present observations indicate that SINEs have generally been derived from tRNAs in invertebrates, as well as in vertebrates, and that retroposition is widely involved in the genetic and structural variability of invertebrate genomes. It has been demonstrated that tRNA(Arg) and tRNA(Lys) appear to be tRNA species found as progenitors of vertebrate SINEs, and the same preference for progenitor species of tRNAs seems also to be a feature of invertebrate SINEs.


Bastadin 21, a novel isobastarane metabolite from the Great Barrier Reef marine sponge Ianthella quadrangulata.
Bastadin 21, a novel tribrominated bastadin with the uncommon isobastarane skeleton, was isolated from the Great Barrier Reef marine sponge Ianthella quadrangulata. The structure was elucidated on the basis of the 1D and 2D NMR and MS data of bastadin 21 and its tetramethyl ether.


[Treatment with a tyrosine-kinase inhibitor of for c-KIT mutation and AML1-ETO double positive refractory acute myeloid leukemia].
Translocation (8;21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, the outcomes associated with KIT mutations in AML1-ETO have not been elucidated. A 16-year-old boy was diagnosed with recurrent AML. Although he underwent hematopoietic stem cell transplantation (HSCT) twice, the leukemia relapsed and grew resistant to several chemotherapies. We began to treat him with imatinib, but stopped on the 31st day as it did not show any effects. Later, we administered dasatinib. However, we discontinued this because he showed severe nasal hemorrhage 87 days after administration of dasatinib. The therapeutic benefit of tyrosine-kinase inhibitor (TKI) was estimated by quantitative analysis of AML1-ETO and the patient's clinical impression. We did not conduct analyses to determine the effective concentration of TKI. The patient has not yet shown any major molecular response. Therefore, we conclude that TKI may be useful for slight palliation of symptoms in KIT-positive AML. However, patients with refractory AML associated KIT mutations in AML1-ETO should not be considered for TKI monotherapy.


Hierarchical Bayesian Logistic Regression to forecast metabolic control in type 2 DM patients.
In this work we present our efforts in building a model able to forecast patients' changes in clinical conditions when repeated measurements are available. In this case the available risk calculators are typically not applicable. We propose a Hierarchical Bayesian Logistic Regression model, which allows taking into account individual and population variability in model parameters estimate. The model is used to predict metabolic control and its variation in type 2 diabetes mellitus. In particular we have analyzed a population of more than 1000 Italian type 2 diabetic patients, collected within the European project Mosaic. The results obtained in terms of Matthews Correlation Coefficient are significantly better than the ones gathered with standard logistic regression model, based on data pooling.


THERMOSENSITIVE BARREN PANICLE (TAP) is required for rice panicle and spikelet development at high ambient temperature.
In cereal plants, the size of the panicle (inflorescence) is a critical factor for yield. Panicle size is determined by a complex interplay of genetic and environmental factors, but the mechanisms underlying adaptations to temperature stress during panicle development remain largely unknown. We identify the rice THERMOSENSITIVE BARREN PANICLE (TAP) gene, which encodes a transposase-derived FAR1-RELATED SEQUENCE (FRS) protein and is responsible for regulating panicle and spikelet development at high ambient temperature. The tap mutants display high temperature-dependent reproductive abnormalities, including compromised secondary branch and spikelet initiation and pleiotropic floral organ defects. Consistent with its thermosensitive phenotype, TAP expression is induced by high temperature. TAP directly promotes the expression of OsYABBY3 (OsYAB3), OsYAB4, and OsYAB5, which encode key transcriptional regulators in panicle and spikelet development. In addition, TAP physically interacts with OsYAB4 and OsYAB5 proteins; phenotypic analysis of osyab4 tap-1 and osyab5 tap-1 double mutants indicates that TAP-OsYAB4/OsYAB5 complexes act to maintain normal panicle and spikelet development. Taken together, our study reveals the novel role of a TE-derived transcription factor in controlling rice panicle development under high ambient temperatures, shedding light on the molecular mechanism underlying the adaptation of cereal crops to increasing environmental temperatures.


Transfer of learning to compensate for impairment by alcohol and visual degradation.
Past research on social drinkers shows that prior experience performing a task in a visually degraded environment results in the reduction of alcohol-induced impairment. It is possible that task experience under alcohol might similarly carry over to reduce impairment from visual degradation. The purpose of this study was to test the symmetry of the transfer of learning between two distinct sources of impairment, visual degradation and alcohol. Psychomotor impairment was measured by a pursuit rotor tracking task. Forty two participants were randomly assigned to one of six treatment groups. Two groups were tested under alcohol after having prior task experience performing with or without visual degradation. Two groups were tested under visual degradation after having prior task experience performing under active (0.65 g/kg) or inactive (placebo) doses of alcohol. The remaining two groups served as controls that tested the learning effects of repeating each active treatment. Clear evidence for asymmetrical transfer of learning was observed. Prior task experience with visual degradation reduced the impairing effects of alcohol. By contrast, prior task experience under alcohol had no effect on impairment produced by visual degradation. Evidence for differential transfer of learning to compensate for alcohol- and visual-degradation-induced impairment is of practical interest, given that the two disturbances commonly co-occur outside the laboratory. Reasons for the asymmetry are unclear, and likely involve differences in mechanisms by which each treatment impairs psychomotor function.


Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition.
The aims of this study were to characterize the structural and microcirculatory changes in single intestinal villi during ischemia and reperfusion and determine the site of action of endothelin (ET)-A receptor inhibition during compromised mucosal perfusion. Small bowel autotransplantation was performed in anesthetized dogs. One group was treated with the ET-A receptor antagonist ETR-p1/fl peptide. The epithelial thickness and villus microcirculatory parameters were observed by orthogonal polarization spectral imaging; the leukocyte-endothelial cell interactions were quantified with fluorescence videomicroscopy. Sixty-minute cold ischemia and 240-min reperfusion induced a decrease in villus functional capillary density and leukocyte-endothelial cell interactions. The epithelial layer was gradually removed, but denuded villi were not observed. ET-A receptor inhibition reduced the leukocyte adherence and attenuated epithelial exfoliation and the decrease in villus functional capillary density. ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel.


[Experimental study of the expression of the bladder wall proteins in bladder outlet obstruction in the rabbit].
To determine the relationship of the bladder wall levels of the contractile proteins: whole actin, beta-actin, alpha-sarcomeric-actina caldesmon and of the Heat Stress Protein HSP-70, with the partial bladder outlet obstruction. It was carried out an experimental study on 43 New-Zealand rabbits. These animals were divided into a control group and six experimental groups with partial bladder outlet obstruction induced by an incomplete tie around the urethra. The experimental groups were defined according the day when the animals were sacrified: at 24 hours, 7 days, 15 days, 1 month, 3 months and 6 months of the obstruction. It was determined in all animals the muscular bladder wall concentration of whole actin, beta-actin, alpha-sarcomeric-actin, caldesmon and HSP-70 protein, according to Western Blotting technique. The results were analyzed by means of ANOVA, using the Scheffe post hoc method. The bladder weight of the obstructed animals increased significantly in two stages: until the day 15 and between the day 15 and the end of the study, corresponding to theoretical phases of initial hypertrophy and compensation. The level of whole actin showed a significant decrease at the beginning of compensation phase, while the beta-actin level increased in the phase of initial hypertrophy and the alpha-sarcomeric-actin level increased at the end of the compensation phase, while the caldesmon and the HSP-70 made it at the end of the initial hypertrophy phase. Analysing our data we conclued that the determination of the caldesmon levels is the marker that better adjusts to the changes associated with partial bladder outlet obstruction in the rabbit.


Burden of chronic cough in the UK: results from the 2018 National Health and Wellness Survey.
Chronic cough, defined as daily cough for at least 8 weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the UK. Study participants were general population respondents to the 2018 UK National Health and Wellness Survey (NHWS). Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matchingon age, sex and the modified Charlson Comorbidity Index. Of 15 000 NHWS respondents, 715 reported chronic cough in the previous 12 months and 918 during their lifetime. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence was 6.2%. Prevalence of chronic cough was higher among older respondents and those with smoking histories. Chronic cough respondents experienced higher rates of severe anxiety and depression in the past 2 weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents visited a healthcare provider in the past 6 months than respondents without chronic cough with a mean of 5.8 and 3.7 visits per respondent, respectively. Adults with chronic cough report lower quality of life, reduced work productivity and greater healthcare resource utilisation than matched controls without chronic cough.


Multiplex polymerase chain reaction for pathogen detection in donor/recipient corneal transplant tissue and donor storage solution.
Corneal transplantation is a safe, reliable method of restoring visual acuity in patients with corneal disorders. Although it has a very high success rate, rejection can still occur, especially if the site is infected. Therefore, seeking to find better ways to manage infection risk, this study investigated a new technique, based on multiplex polymerase chain reaction (mPCR), to identify pathogens, including viruses, bacteria, and fungi, in corneal transplantation recipient sites, donor corneas and the donor cornea storage solution. The subjects comprised 50 patients who underwent corneal transplantation at Tohoku University Hospital between July 2014 and April 2015. We obtained extracted (recipient) cornea samples in 37 cases, donor cornea samples in 50 cases, and corneal storage solution samples in 50 cases (18 of these 50 samples contained DNA). Herpes simplex virus type 1 DNA was detected in four recipient corneas, Parvovirus B19 DNA was detected in two recipient corneas, Human herpes virus type 6 was detected in two donor corneas, and Aspergillus DNA was detected in one corneal storage solution sample. Thus, mPCR successfully identified pathogenic DNA in corneal tissues and storage solution, suggesting that evaluation with mPCR may improve the ability to predict the risk of infection after corneal transplantation.


Long read transcriptome sequencing of a sugarcane hybrid and its progenitors, Saccharum officinarum and S. spontaneum.
Commercial sugarcane hybrids are derivatives from Saccharum officinarum and Saccharum spontaneum hybrids containing the full complement of S. officinarum and a few S. spontaneum chromosomes and recombinants with favorable agronomic characters from both the species. The combination of the two sub-genomes in varying proportions in addition to the recombinants presents a challenge in the study of gene expression and regulation in the hybrid. We now report the transcriptome analysis of the two progenitor species and a modern commercial sugarcane hybrid through long read sequencing technology. Transcripts were profiled in the two progenitor species S. officinarum (Black Cheribon), and S. spontaneum (Coimbatore accession) and a recent high yielding, high sugar variety Co 11015. The composition and contribution of the progenitors to a hybrid with respect to sugar, biomass, and disease resistance were established. Sugar related transcripts originated from S. officinarum while several stress and senescence related transcripts were from S. spontaneum in the hybrid. The hybrid had a higher number of transcripts related to sugar transporters, invertases, transcription factors, trehalose, UDP sugars, and cellulose than the two progenitor species. Both S. officinarum and the hybrid had an abundance of novel genes like sugar phosphate translocator, while S. spontaneum had just one. In general, the hybrid shared a larger number of transcripts with S. officinarum than with S. spontaneum, reflecting the genomic contribution, while the progenitors shared very few transcripts between them. The common isoforms among the three genotypes and unique isoforms specific to each genotype indicate that there is a high scope for improvement of the modern hybrids by utilizing novel gene isoforms from the progenitor species.


The nocturnal increase in growth hormone is not the cause of the nocturnal increase in serum osteocalcin.
Osteoblast activity, as measured by the serum osteocalcin (OC) concentration, increases at night in both normal women and women with postmenopausal osteoporosis. Because there is also a physiological increase in GH during deep sleep and the nocturnal increases in serum OC and GH concentrations both become less pronounced with advancing age, we used somatostatin (SMS) infusion to evaluate the effect of suppression of the nocturnal GH increase on the expected increase in serum OC. Serum OC levels were measured during an 8-h iv infusion of SMS and during a similar infusion of isotonic saline (control night) in five young women (mean age +/- SE, 21 +/- 2 yr). SMS significantly (P less than 0.05) decreased secretion of endogenous GH. The mean increases in serum OC concentration were similar during SMS infusion and control nights. Furthermore, the nocturnal pattern of increase in serum OC levels during GH or saline infusions did not differ. From these data, we conclude that the nocturnal increases in serum OC and GH levels are not related.


Manatí Medical Center Sepsis Management Epidemiological Study.
Sepsis is the combination of infection and physiological changes known as the systemic inflammatory response syndrome. There have been improvements in mortality rates and outcomes of septic patients based on "Surviving Sepsis Campaign" guidelines. Current management of sepsis at our Institution follows no specific mandatory protocols. This study aimed to verify the incidence and outcome of sepsis in Manati Medical Center, Puerto Rico. An observational retrospective study was conducted. All the Emergency Department admissions from May 1/ to October 31/ 2013 were screened for sepsis per ICD-9 code. For all included patients, demographic and clinical data at ED admission were collected. During this period 8931 patients were admitted and 148 met criteria for sepsis and related conditions. The overall mortality rate was 43.91%. Mortality increased with age, from 10.52% among ≤ 44 years old to 68.75% in those ≥ 85 years old. The main infection sources were respiratory (32.66%) and urinary tract (24.62%). Mean age among non-survivors was 10.8 years higher than the survivor group (95% Cl 5.2-1 6.5, p < 0.05). Multivariate analysis showed an increased fatality rate associated to severity of sepsis (HR 1.33; 95% Cl; 1.03-1.72, p = 0.02) and the APACHE2 score (HR 1.05; 95% Cl, 1.01-1.09 p = 0.03). Our data suggests that sepsis is an important problem to consider. We strongly encourage an institutional standardized protocol to diminish the mortality impact. Our results will allow adequate preventive strategies to improve early diagnosis, mortality rates and outcomes of septic patients.


Perspective: successfully negotiating the clerkship years of medical school: a guide for medical students, implications for residents and faculty.
Medical students face significant learning and cultural challenges during the transition from the classroom to the clinical setting. The authors recommend that students be proactive in preparing themselves for this difficult journey by understanding and applying principles of adult learning. To guide students in this preparation, the authors propose a model that incorporates adult learning principles into a cycle emphasizing reflective practice. This model, based on the Kolb learning cycle, consists of five sequential steps: (1) preparing for the clinical setting, (2) experiencing the clinical setting, (3) reflecting on experience, (4) conceptualizing new approaches, and (5) testing new approaches on return to the clinical setting. This fifth stage in the cycle completes the first iteration. The cycle never ends, however; experimentation leads to new reflection, which in turn leads to new approaches and new experience.


Vasoactive intestinal polypeptide in the normal and unstable bladder.
The possible involvement in idiopathic detrusor instability of a newly discovered type of autonomic nerve containing vasoactive intestinal polypeptide (VIP) has been studied. Immunocytochemistry and radioimmunoassay, using specific antibodies against VIP, were carried out on 20 biopsy specimens from the bladders of patients with detrusor instability and 20 specimens from control patients. The concentration of VIP in the unstable bladders was found to be markedly reduced from 36.52 +/- 4.8 pmol/g (mean +/- SEM) to 7.62 +/- 1.84 pmol/g (P less than 0.01). The number of VIP immunoreactive nerves was greatly decreased in all of the layers but particularly in the muscle layer of the unstable bladder in comparison with the controls. These findings may provide important information about the mechanism of this disorder.


Using Clinical Instructor Perceptions to Improve a Pilot Simulation Course.
Little is known about clinical instructors' perceptions of student decision-making in relation to the block sequencing of simulation and traditional clinical experiences. Focus groups were conducted with 12 clinical instructors. Three common threads emerged from the data: right away, anxious but more confident, and scary and unsafe. Instructors noted that the more patient care experiences encountered, the more students developed efficient clinical decision-making skills. Major safety concerns regarding medication administration were identified, resulting in additional safety parameters instituted in the simulated environment.


Impact of superselective transarterial infusion therapy of high-dose cisplatin on maxillary cancer with orbital invasion.
We have been performing the superselective transarterial infusion of high-dose cisplatin for advanced maxillary cancer since 1998 and the local control rate, disease free survival rate, and organ preservation have improved markedly compared with our former therapy. This study evaluates the effectiveness of superselective transarterial infusion therapy by using high-dose cisplatin on maxillary cancer with orbital invasion. We treated 23 patients with maxillary cancer by using superselective transarterial infusion therapy with high-dose cisplatin and concomitant radiation therapy for 10 years. Of all patients, 15 showed orbital invasion, with 11 of these tumors fed by both internal maxillary and ophthalmic arteries. In all patients, we performed superselective transarterial infusion therapy via the internal maxillary artery and/or the other feeding branches from the external carotid artery. After the operation, we determined whether a pCR had occurred by checking for the presence of viable cells. In addition, we calculated the overall survival rate, preservation rate of the eyeball, and disease-free survival rate. For all 23 patients, pCR and overall survival rates were 95.7% and 78.4%, respectively. To date, 2 of these patients died of lung metastasis without local recurrence. For the 15 patients with orbital invasion, the respective pCR and disease-free survival rates were 93.3% and 87.5%. Eyeballs were preserved in all patients, and local recurrence occurred in only 1 patient, at the inferior wall of the maxillary sinus (not in the orbit). Superselective transarterial infusion therapy with high-dose cisplatin remarkably improved the local control rate and disease-free survival rate of maxillary cancer. Even in patients with orbital invasion, a high local control rate was achieved, with preservation of the eyeball, through infusion only into branches of the external carotid artery.


Defects in meiotic chromosome segregation lead to unreduced male gametes in Arabidopsis SMC5/6 complex mutants.
Structural maintenance of chromosome 5/6 (SMC5/6) complex is a crucial factor for preserving genome stability. Here, we show that mutants for several Arabidopsis (Arabidopsis thaliana) SMC5/6 complex subunits produce triploid offspring. This phenotype is caused by a meiotic defect leading to the production of unreduced male gametes. The SMC5/6 complex mutants show an absence of chromosome segregation during the first and/or the second meiotic division, as well as a partially disorganized microtubule network. Importantly, although the SMC5/6 complex is partly required for the repair of SPO11-induced DNA double-strand breaks, the nonreduction described here is SPO11-independent. The measured high rate of ovule abortion suggests that, if produced, such defects are maternally lethal. Upon fertilization with an unreduced pollen, the unbalanced maternal and paternal genome dosage in the endosperm most likely causes seed abortion observed in several SMC5/6 complex mutants. In conclusion, we describe the function of the SMC5/6 complex in the maintenance of gametophytic ploidy in Arabidopsis.


Microsurgical two-stage reconstruction of the thumb. Case report.
A 40-year-old patient presented with traumatic amputation of the thumb and index finger. The second metacarpal bone fragment was transposed to lengthen the first metacarpal bone. A free flap from the lateral forearm was used to reconstruct the thenar region. Later, the second free toe-to-hand transfer was done from which he made a good recovery, achieving active flexion and extension in all joints.


Observation of a helical self-organized state in a compact toroidal plasma.
A nonaxisymmetric stable magnetohydrodynamic (MHD) equilibrium within a prolate cylindrical conducting boundary has been produced experimentally. It has m=1 azimuthal symmetry, helical distortion, and flat lambda profile, all in agreement with the computed magnetically relaxed minimum magnetic energy Taylor state. Despite varied initial conditions determined by two helicity injectors on the device, this same equilibrium consistently emerges as the final state. These results therefore describe a new example of self-organization in an MHD plasma.


Sex- and age-specific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults.
Diagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking. Sixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature. Most ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night. Sex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.


The symptoms and management of myalgic encephalomyelitis.
Myalgic encephalomyelitis (ME), which is also known as chronic fatigue syndrome, is a chronic, debilitating illness with varying symptoms and patterns of progression. Research has yet to establish its aetiology and pathogenesis, and there is no cure. A number of management strategies have proved effective, but these should always be tailored to the individual patient. Although no drug treatment has been developed specifically for ME, therapies used to manage the same symptoms in other conditions can provide some relief. Treatment and management should be planned in partnership with the patient.


Recurrent Perihepatic Abscesses Arising from a Gastric Remnant Leak: Delayed Complication of a Revision Roux-en-Y Gastric Bypass.
Roux-en-Y gastric bypass is a procedure commonly used for weight loss associated with improved outcomes and decreased complications when compared to some counterparts. The procedure involves restriction of the stomach that is achieved by creation of a gastric pouch and bypass of the duodenum and a portion of the jejunum to aid in restrictive and malabsorptive weight loss. While many complications, both early and late, have been described following the procedure, recurrent perihepatic abscess has not been described in the literature. We present a case of a 66-year-old woman with recurrent extrahepatic abscesses following revision of a Roux-en-Y gastric bypass.


Macronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children.
Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. We defined the burden of life-threatening (O(2) saturation [O(2) sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children's pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O(2) sat less than 93% on admission were included. Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5-2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV(+)), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4-1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15-9.44] to 7.36 [95% CI, 2.41-22.5] versus the lowest quartile). Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.


Subwavelength acoustic metamaterial panels for underwater noise isolation.
Acoustically thin metamaterial underwater noise isolation panels have been developed that provide as much as 16 dB of noise isolation for a panel with a thickness just 160th of the wavelength in the host medium (fresh water) at 2.5 kHz. The panels are composed of thin layers of neoprene rubber and polyoxymethylene containing air-filled voids. The level of isolation provided by the panels is shown to correlate positively with the volume fraction of air voids within the panel.


Mechanism of enhanced oxygen transfer in fermentation using emulsified oxygen-vectors.
Limitations of oxygen transfer in fermentation can be solved using auxiliary liquids immiscible in the aqueous phase. The liquids (called oxygen-vectors) used in this study were hydrocarbon (n-dodecane) and perfluorocarbon (forane F66E) in which oxygen is highly soluble (54.9 mg/L in n-dodecane and 118 mg/L in forane F66E at 35 degrees C in contact with air at atmospheric pressure). It has been demonstrated that the use of n-dodecane emulsion in a culture of Aerobacter aerogenes enabled a 3. 5-fold increase of the volumetric oxygen transfer coefficient(k(L)a) calculated on a per-liter aqueous phase basis. The droplet size of the vector played a crucial role in the phenomena. When a static contact between gas bubble and vector droplet was established in water, the vector covered the bubble, in agreement with positive values of the spreading coefficient for these fluids. The determination of the oxygen transfer coefficients (k(L)) in a reactor with a definite interfacial area enabled the main resistance to be located in the boundary layer of the waterside either for a gas-water or a vector-water interface. Because oxygen consumption by weakly hydrophobic cells can only occur in the aqueous phase, the oxygen transfer is achieved according to the following pathway: gas-vector-water-cell. Finally, a mechanism for oxygen transfer within this four-phased system is proposed.