Bioinformatic Analysis of the Effect of the Sirtuin Family on Differentiated Thyroid Carcinoma.
A growing body of experimental evidence suggests that sirtuins (SIRTs) are associated with tumorigenesis in differentiated thyroid cancer (DTC). Nevertheless, the involvement of SIRTs in the pathogenesis of DTC and their clinical value remain ill-defined and should be thoroughly examined. We explored the transcription of SIRTs and survival data of patients with DTC by the systematic utilization of bioinformatics to analyze data of publicly accessible databases including Oncomine, cBioPortal, Kaplan-Meier Plotter, Gene Expression Profiling Interactive Analysis (GEPIA), Protein Atlas, LinkedOmics, and GSCALite. The examination of gene expression profiles showed that SIRT2, SIRT3, SIRT4, SIRT5, and SIRT6 were downregulated in DTC tissues compared with the normal thyroid tissues. The decreased expression levels of SIRT2, SIRT4, and SIRT5 were correlated with advanced tumor stages. The survival results showed that the increased SIRT4 mRNA expression level was associated with improved overall survival (OS) in the DTC patients. In addition, patients with DTC with high SIRT2, SIRT3, SIRT4, and SIRT5 mRNA levels had higher disease-free survival (DFS). These results showed that SIRT2, SIRT3, SIRT4, SIRT5, and SIRT6 are potential targets for precise treatment of DTC patients and that SIRT2, SIRT3, SIRT4, and SIRT5 are novel potential biomarkers for the prognosis of DTC.


Capture of Gaseous Iodine in Isoreticular Zirconium-Based UiO-n Metal-Organic Frameworks: Influence of Amino Functionalization, DFT Calculations, Raman and EPR Spectroscopic Investigation.
A series of Zr-based UiO-n MOF materials (n=66, 67, 68) have been studied for iodine capture. Gaseous iodine adsorption was collected kinetically from a home-made set-up allowing the continuous measurement of iodine content trapped within UiO-n compounds, with organic functionalities (-H, -CH3 , -Cl, -Br, -(OH)2 , -NO2 , -NH2 , (-NH2 )2 , -CH2 NH2 ) by in-situ UV-Vis spectroscopy. This study emphasizes the role of the amino groups attached to the aromatic rings of the ligands connecting the {Zr6 O4 (OH)4 } brick. In particular, the preferential interaction of iodine with lone-pair groups, such as amino functions, has been experimentally observed and is also based on DFT calculations. Indeed, higher iodine contents were systematically measured for amino-functionalized UiO-66 or UiO-67, compared to the pristine material (up to 1211 mg/g for UiO-67-(NH2 )2 ). However, DFT calculations revealed the highest computed interaction energies for alkylamine groups (-CH2 NH2 ) in UiO-67 (-128.5 kJ/mol for the octahedral cavity), and pointed out the influence of this specific functionality compared with that of an aromatic amine. The encapsulation of iodine within the pore system of UiO-n materials and their amino-derivatives has been analyzed by UV-Vis and Raman spectroscopy. We showed that a systematic conversion of molecular iodine (I2 ) species into anionic I- ones, stabilized as I- ⋅⋅⋅I2 or I3 - complexes within the MOF cavities, occurs when I2 @UiO-n samples are left in ambient light.


Dual-modal imaging and photodynamic therapy using upconversion nanoparticles for tumor cells.
Here we synthesized silica-coated NaYF4:Yb,Tm@NaGdF4 nanoparticles with hypocrellin photosensitizers covalently incorporated inside the silica shells, combining dual modal imaging and photodynamic therapy (PDT) functions together. Under excitation at 980 nm, the tumor-targeting specificity of the as-prepared nanomaterials efficiently enhanced as folic acid (FA) was conjugated. The internalization of UCNPs@SiO2@hypocrellin A-FA in HeLa cells and HEK-293 cells was observed by confocal microscopy and in vitro magnetic resonance imaging (MRI), which demonstrated that the as-prepared nanocomposites have the ability to target folate receptor (FR) (+) cells. Moreover, magnetic resonance (MR) measurements also demonstrated that the as-prepared nanocomposites could be used as a contrast agent for MRI. All these results showed the feasibility and potential of the as-prepared nanocomposites for simultaneous imaging and PDT application.


Primary adenomatoid tumor of the testis: report of a case and review of literature.
Adenomatoid tumor (AT) is an extremely rare benign tumor in the testis of infants. A case of 14-month-old boy with testicular adenomatoid tumor was reported in this study. On physical examination, a smooth solid nodule sized 8 mm could be palpated with little tenderness on the head of the right testis. It could be clearly revealed by B ultrasonic scanning and computerized tomography. The patient underwent right radical orchiectomy. In postoperative histopathological study, the tumor was characterized by diffuse sheets of epithelioid cell and desmo-stroma structures. There was positive immunohistochemical staining of mesothelioma-associated antigens. The tumor should be differentiated from the tumor of the male genital tract including benign and malignant tumors of both epithelial and stromal origin. And we followed the case and no nodule was found in his scrotum by physical examination and scrotal ultrasonography after 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months. These findings have important implications that the histogenesis of adenomatoid tumor of the testis is unclear yet. The diagnosis depends on pathologic studies, and should be differentiated from paratesticular malignant mesothelioma and sclerosed lipogranuloma. Radical surgery is the common choice, and as a result of getting a good prognosis.


Health care-seeking behavior for childhood diarrhea in Mirzapur, rural Bangladesh.
We evaluated patterns of health care use for diarrhea among children 0-59 months of age residing in Mirzapur, Bangladesh, using a baseline survey conducted during May-June 2007 to inform the design of a planned diarrheal etiology case/control study. Caretakers of 7.4% of 1,128 children reported a diarrheal illness in the preceding 14 days; among 95 children with diarrhea, 24.2% had blood in the stool, 12.2% received oral rehydration solution, 27.6% received homemade fluids, and none received zinc at home. Caretakers of 87.9% sought care outside the home; 49.9% from a pharmacy, and 22.1% from a hospital or health center. The primary reasons for not seeking care were maternal perception that the illness was not serious enough (74.0%) and the high cost of treatment (21.9%). To improve management of childhood diarrhea in Mirzapur, Bangladesh, it will be important to address knowledge gaps in caretakers' assessment of illness severity, appropriate home management, and when to seek care in the formal sector. In addition, consideration should be given to inclusion of the diverse care-giving settings in clinical training activities for diarrheal disease management.


The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains.
The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently divergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies.


Characterisation and toxicity of Bacillus thuringiensis strains from hazelnut pests and fields.
In order to find and identify more toxic insecticidal Bacillus thuringiensis Berliner (Bt) strains, a survey was carried out of B. thuringiensis isolate pests belonging to Coleoptera, Lepidoptera and Diptera and from soils in hazelnut fields. Of 16 isolates having Bacillus cereus-B. thuringiensis morphology, eight were classified as B. thuringiensis because of the production of parasporal delta-endotoxin crystals. In this study, eight isolates of B. thuringiensis from hazelnut pests (isolates Bn1, Mm2, Mnd and Xd3) and from hazelnut soils (isolates 6, 27, 40 and 46) have been characterised in detail. These isolates were compared with reference strains by electron microscopy, SDS-PAGE analysis, cry gene content, serological test and insecticidal activity. Results indicate that Bn1 and MnD are B. thuringiensis subsp. kurstaki, and Mm2 and Xd3 are B. thuringiensis subsp. tenebrionis. In addition, isolate 6 is B. thuringiensis subsp. israelensis, isolates 27 and 46 are B. thuringiensis subsp. kumamotoensis and isolate 40 is B. thuringiensis subsp. indiana. The four B. thuringiensis isolates from hazelnut pests may be valuable as biological control agents against coleopteran and lepidopteran insects.


The ins and outs of molecular encapsulation.
Molecular capsules can act as hosts for appropriate guests, and bring them into well-defined nanoenvironments. Various spectroscopic methods have been used to deduce the mechanism of guest exchange in such systems. Generally, the guests get in and out of capsules through the opening and closing of host "flaps" but smaller capsules can exchange simply by dissociation of the host subunits.


Deep Learning-Based Image Reconstruction for CT Angiography of the Aorta.
To evaluate the impact of a novel, deep-learning-based image reconstruction (DLIR) algorithm on image quality in CT angiography of the aorta, we retrospectively analyzed 51 consecutive patients who underwent ECG-gated chest CT angiography and non-gated acquisition for the abdomen on a 256-dectector-row CT. Images were reconstructed with adaptive statistical iterative reconstruction (ASIR-V) and DLIR. Intravascular image noise, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) were quantified for the ascending aorta, the descending thoracic aorta, the abdominal aorta and the iliac arteries. Two readers scored subjective image quality on a five-point scale. Compared to ASIR-V, DLIR reduced the median image noise by 51-54% for the ascending aorta and the descending thoracic aorta. Correspondingly, median CNR roughly doubled for the ascending aorta and descending thoracic aorta. There was a 38% reduction in image noise for the abdominal aorta and the iliac arteries, with a corresponding improvement in CNR. Median subjective image quality improved from good to excellent at all anatomical levels. In CT angiography of the aorta, DLIR substantially improved objective and subjective image quality beyond what can be achieved by state-of-the-art iterative reconstruction. This can pave the way for further radiation or contrast dose reductions.


Multiple infarcts and hemorrhages in the central nervous system of a dog with cerebral amyloid angiopathy: a case report.
β-amyloid (Aβ) can accumulate in the brain of aged dogs, and within vessels walls, the disease is called cerebral amyloid angiopathy (CAA). In humans, Alzheimer's disease and CAA are strongly correlated with cerebrovascular disease. However, in dogs, this association has not been extensively studied yet. The present report highlights the pathological and clinical features of a concomitant cerebrovascular disease and amyloid precursor protein (APP) accumulation in the brain of a dog. A female, 16-year-old, Standard Poodle with a one-year history of cognitive deficits presented with an acute onset of right-sided postural reaction deficit and circling, left-sided head tilt, positional nystagmus, and ataxia. Due to poor prognosis the dog was euthanized, and pathological examination of the brain revealed an acute lacunar infarction within the thalamus extending to rostral colliculus. Additional findings included subacute and chronic areas of ischemia throughout the brain and areas of hemorrhage within the medulla. Immunolabeling revealed APP deposition within intraparenchymal vessels of frontal, temporal and occipital cortex, hippocampus, diencephalon, mesencephalon and myelencephalon, besides meningeal vessels walls. Glial fibrillary acidic protein (GFAP) immunolabeling showed marked astrocytosis around the acute area of infarction and within chronic areas of ischemia. Histological examination of the brain along with immunohistochemistry results showed a concomitant APP, which is an Aβ precursor, accumulation within the neuroparenchyma and vessels (CAA) with histological evidences of a cerebrovascular disease in an aged dog. This report shows that APP accumulation in the brain can occur concomitantly to a severe cerebrovascular disease in a dog. Further studies are necessary to elucidate if cerebrovascular disease is associated with Aβ accumulation in the brain of dogs.


Enhanced patterns of oriented edge magnitudes for face recognition and image matching.
A good feature descriptor is desired to be discriminative, robust, and computationally inexpensive in both terms of time and storage requirement. In the domain of face recognition, these properties allow the system to quickly deliver high recognition results to the end user. Motivated by the recent feature descriptor called Patterns of Oriented Edge Magnitudes (POEM), which balances the three concerns, this paper aims at enhancing its performance with respect to all these criteria. To this end, we first optimize the parameters of POEM and then apply the whitened principal-component-analysis dimensionality reduction technique to get a more compact, robust, and discriminative descriptor. For face recognition, the efficiency of our algorithm is proved by strong results obtained on both constrained (Face Recognition Technology, FERET) and unconstrained (Labeled Faces in the Wild, LFW) data sets in addition with the low complexity. Impressively, our algorithm is about 30 times faster than those based on Gabor filters. Furthermore, by proposing an additional technique that makes our descriptor robust to rotation, we validate its efficiency for the task of image matching.


Exogenous hydrogen sulfide (H2S) reduces blood pressure and prevents the progression of diabetic nephropathy in spontaneously hypertensive rats.
The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H2S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in spontaneously hypertensive rats (SHR) that were diabetic. Eighteen SHR were divided into three groups: SHR, SHR diabetic, and SHR diabetic treated with a group of Wistar-Kyoto rats serving as normotensive nondiabetic control. Diabetes was induced with streptozotocin (STZ) in two groups and one diabetic group received sodium hydrosulfide (NaHS), a H2S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H2S levels, creatinine concentrations, and electrolytes were measured on three different occasions throughout the 35-day period. Diabetic SHR had higher blood pressure, lower plasma and urinary H2S levels, and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance, and decreased urinary sodium-to-potassium ratio and renal cortical blood perfusion. NaHS reduced blood pressure, increased H2S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H2S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.


Prevalence, biosecurity factor, and antimicrobial susceptibility analysis of Salmonella species isolated from commercial duck farms in Korea.
Duck meat consumption in South Korea has increased in recent years, but no standard about duck farm-specific biosecurity and hygiene guidelines have yet been established. We here investigated Salmonella contamination levels in duck farms to evaluate biosecurity and hygiene practices. We collected 1,116 environmental samples from 31 duck farms in Jeonnam Province, South Korea. The Salmonella-positive farm rate dramatically increased, from 22.6 to 71.0%, on introduction of ducklings. As the ducklings aged 4-6 wk, the positive rate slightly decreased to 64.5%. The Salmonella detection rate on each sampled surface, such as the feed pan (34.4%), wall (33.9%), litter (32.3%), and nipples (24.2%), was highest at 3 wk of age. The most frequently detected Salmonella serovars were Salmonella London (22.2%), Salmonella Albany (21.6%), Salmonella Bareilly (17.0%), and Salmonella Indiana (16.5%). Implementation of cleaning and disinfection procedures, rodent control, and metal house walls significantly lowered the prevalence of Salmonella (P < 0.001, P < 0.01, and P < 0.05, respectively). A high proportion of Salmonella isolates exhibited antimicrobial resistance: 100 and 62.9% exhibited resistance to erythromycin and nalidixic acid, respectively. Furthermore, a majority of S. Albany and all Salmonella Enteritidis isolates were multidrug resistant. These results indicate the level of Salmonella contamination in duck farm environments in Korea is high. Good biosecurity and hygiene practices are the most effective measures for controlling Salmonella contamination.


[Exercise therapy for obesity].
It is very difficult for an obese person to lose weight or maintain a standard body weight, even when exercise therapy is carried out. However, in studies in recent years, it has been reported that the risk of metabolic diseases may be reduced, even regarding physical activities that do not meet the guidelines (for physical activity). Physical activities that allow for sustainable everyday life, rather than goals that are difficult to accomplish, are therefore required in future exercise therapies.


Ultrastructure and electron immunocytochemistry of insulin-producing B-cell tumors from transgenic mice: comparison with counterpart human tumors.
This paper reports on an ultrastructural and electron-microscopic immunocytochemical study of pancreatic B cells from normal mice, pancreatic B cells and derivative tumors from transgenic mice, and tissue from human pancreatic B-cell tumors. In normal and neoplastic B cells from both species, typical immature and mature beta-granules (with spherical cores of variable density) were observed, whereas typical beta-granules with a crystalloid core were only present in human B cells (normal and tumor). A small number of atypical granules were found in distinct neoplastic cells which contained no typical beta-granules. The atypical granules were smaller (100-200 nm diameter) than typical beta-granules (250-450 nm diameter) seen in other cells. Immunoreactivity for proinsulin was localized only to immature granules, whereas insulin and C-peptide immunoreactivities were demonstrated in atypical, immature, and mature granules. In transgenic mouse and human B-cell tumors, insulin immunoreactivity was consistently weaker than the immunostaining for C-peptide. An intragranular, topographic segregation of immunoreactive C-peptide was observed in a population of transgenic tumor cells. Our results showed similarities in antigenic distribution and only slight differences in morphology between human and mouse B cells. Therefore, the transgenic mouse system may prove to be an effective model for studying mammalian B-cell tumorigenesis.


Annexins in the secretory pathway.
Among the multiplicity of roles suggested for proteins of the annexin family, those implicating these proteins in regulated exocytosis remain among the most convincing. Studies in this area of annexin biology have focused on annexin II, which because of its unusually low Ca(2+)-requirement for phospholipid-binding has many of the requisite properties of a membrane fusogenic Ca2+ sensor. Other annexins are also good candidates for exocytotic mediators, especially annexins I and VII, which have strong vesicle-aggregating activities. In contrast, annexin VI appears to block vesicle aggregation, perhaps acting as a negative regulator of exocytosis. In this review, we consider the evidence for and against annexins having functions in the secretory pathway.


Physiologic and anesthetic alterations on spinal-sciatic evoked responses in swine.
Spinal-sciatic evoked responses (ScER) have been used successfully to monitor the integrity of the anterior spinal cord during spinal surgery. To evaluate the effects of hypercarbia, hypocarbia, induced hypotension, and hypothermia on the ScER, ten swine anesthetized with ketamine were subjected to varying levels of PaCO2, hypothermia, and induced hypotension. During variation of one physiologic variable, the other variables were closely regulated. There were no significant changes associated with variations in PaCO2. Decreasing temperature provided a consistent increase in latency (r = -0.78, P < 0.001) with no significant alteration in amplitude. Graded hypotension caused little increase in latency (3.2% at 30 mm Hg). The amplitude decrease averaged 23% at 60 mm Hg with a maximal decrease of 50% at 30 mm Hg. To study inhaled anesthetics, 21 swine anesthetized with ketamine were subjected to nitrous oxide (50% and 70%). After termination of the nitrous oxide, one of the potent inhaled anesthetics (n = 7 each) was administered in 0.25 minimum alveolar concentration (MAC) increments. Nitrous oxide caused a significant decrease in amplitude (average 43% and 61% at 50% and 70%) with minimal changes in latency. There was a dose-dependent decrease in amplitude and increase in latency with all inhaled anesthetics. The ScER disappeared at 1.0 MAC with all anesthetics. There were no differences between effects of equipotent concentrations of inhaled anesthetics. These findings may be helpful in the interpretation of the ScER response during anesthesia and surgery.


Highly Efficient and Photostable Ternary Organic Solar Cells Enabled by the Combination of Non-Fullerene and Fullerene Acceptors with Thienopyrrolodione-based Polymer Donors.
Two polymer donors, PFBDT-8ttTPD and PClBDT-8ttTPD, consisting of halogenated thiophene-substituted benzo[1,2-b:4,5-b']dithiophene and alkyl-substituted thieno[3,2-b]thiophene linked thieno[3,4-c]pyrrole-4,6(5H)-dione, were designed and synthesized for the evaluation of photovoltaic performances. The fabricated IT-4F-based organic solar cells (OSCs) exhibited maximum power conversion efficiency (PCE) values of 12.81 and 11.12% for PFBDT-8ttTPD and PClBDT-8ttTPD, respectively. Furthermore, PFBDT-8ttTPD:Y6 showed significantly improved PCE (15.05%) due to the extended light harvesting in the broad solar spectrum, whereas the PClBDT-8ttTPD:Y6 displayed relatively low PCE (10.02%). A ternary system incorporating PC71BM as the third component into bulk-heterojuction composites (PFBDT-8ttPTD:non-fullerene) was investigated with the aim of utilizing the advantages of PC71BM. As a result, PFBDT-8ttTPD:IT-4F:PC71BM exhibited an improved PCE (13.67%) compared to that of the corresponding binary OSC. In particular, ternary OSC of PFBDT-8ttTPD:Y6:PC71BM showed outstanding photovoltaic performance (PCE = 16.43%) as well as photostability, retaining approximately 80% of the initial PCE after 500 h under continuous illumination. The introduction of a small amount of PC71BM resulted in favorable and dense molecular packing with improved crystallinity as well as enhanced charge carrier mobility for efficient OSC.


An unusual presentation of all the mandibular anterior teeth with two root canals--a case report.
A rare case of two root canals in all mandibular anterior teeth is presented. The patient initially reported for the treatment of mandibular right central and lateral incisors. However, radiographic evaluation revealed variant root canal and apical foramen patterns.


Diagnostic Accuracy of H. pylori Status by Conventional Endoscopy: Time-Trend Change After Eradication and Impact of Endoscopic Image Quality.
To assess the time trend of diagnostic accuracy of pre- and post-eradication H. pylori status and interobserver agreement of gastric atrophy grading. A series 100 of conventional endoscopic image sets taken from subjects undergoing gastric cancer screening at a polyclinic were evaluated by 5 experienced assessors. Each assessor independently examined endoscopic findings according to the Kyoto classification and then determined the H. pylori status (never, current, or past infected). Gastric atrophy was assessed according to the Kimura-Takemoto classification and classified into 3 grades (none/mild, moderate, or severe). The image series that ≥3 assessors considered to have good quality were arbitrarily defined as high-quality image (HQI) series, and the rest were defined as low-quality image (LQI) series. The overall diagnostic accuracy of H. pylori status was 83.0%. It was lowest in subjects with current infection (54%), gradually increased at 1 year (79%, P < 0.001) and 3 years (94.0%, P = 0.002), but then did not significantly change at 5 years (91.0%, P = 0.420) after eradication. The rate of LQI series was 28%. The overall diagnostic accuracy of H. pylori status dropped from 88.9% to 67.9% (P < 0.001), and the mean kappa value on gastric atrophy grading dropped from 0.730 to 0.580 (P = 0.002) in the HQI and LQI series, respectively. Diagnostic accuracy of H. pylori status increased over time after eradication. LQI series badly affected the diagnostic accuracy of H. pylori status and the level of agreement when grading gastric atrophy.


Beclin‑1 exerts protective effects against cerebral ischemia‑reperfusion injury by promoting DNA damage repair through a non‑autophagy‑dependent regulatory mechanism.
Cerebral ischemia‑reperfusion (I/R) can result in severe brain injury, for which there are no optimal treatment options. I/R is often accompanied by increased autophagy. Beclin‑1, a central player in autophagy, has been extensively studied in I/R; however, to date, at least to the best of our knowledge, there are no definitive descriptions of its specific role. Thus, the aim of the present study was to explore the regulatory role played by Beclin‑1 in I/R. In vivo experiments were performed using an animal model of brain I/R with male Sprague‑Dawley rats. Brain tissue damage was observed using 2,3,5‑triphenyltetrazolium chloride, and hematoxylin and eosin staining. Tissue apoptosis levels were evaluated using a TUNEL assay, as well as western blot analysis. Immunofluorescence together with western blot analysis was used to detect autophagy in the tissues. Immunohistochemistry and western blot analysis were used to analyze DNA double‑stranded breaks (DSBs). Moreover, HT22 cells overexpressing Beclin‑1 were subjected to oxygen glucose deprivation/reoxygenation injury to simulate I/R pathological damage in vitro. Apoptosis was assessed using TUNEL and flow cytometric assays in this in vitro model, and autophagy was assessed using immunofluorescence and western blot analysis. The DSBs of the cells were analyzed using western blot analysis. I/R activated autophagy and induced DSBs. Autophagy inhibitors decreased brain tissue damage and reduced cell apoptosis; however, the degree of decrease in damage and apoptosis was not highly associated with the change in autophagy, and the frequency of DSBs slightly increased. The overexpression of Beclin‑1 in neurons significantly attenuated I/R‑induced damage and promoted DSB repair. On the whole, the present study demonstrates that Beclin‑1 protects neurons from ischemic damage through the non‑autophagy‑dependent regulation of DNA repair processes.


Experimental transferable vascular bed for laryngotracheal reconstruction: further observations.
Free fascia flaps have proven most reliable in providing a vascular bed for an epithelial free graft without adding bulk. They may be a useful tool for laryngotracheal reconstruction. A free flap consisting of a vascular network running in connective tissue can be developed on the rabbit external ear. The vascular characteristics of this flap were examined to test the reliability of the transferable vascular bed in laryngotracheal repair. The perichondrial free flap is useful for bringing an internal lining inside the lumen and for circumferential protection of supporting tissue. However, the natural tendency for surface contraction of perichondrium is a major disadvantage.


Role of insulin in the neuroendocrine control of reproduction.
Infertility associated with insulin resistance is characterised by abnormal hormone secretion by the hypothalamus, pituitary gland and gonads. These endocrine tissues can maintain insulin sensitivity even when tissues such as the muscle and liver become insulin-resistant, resulting in excessive insulin stimulation as hyperinsulinaemia develops. Experiments conducted to determine the role of neuronal insulin signalling in fertility were unable to recapitulate early findings of hypogonadotrophic hypogonadism in mice lacking insulin receptors throughout the brain. Rather, it was eventually shown that astrocytes critically mediate the effects of insulin on puberty timing and adult reproductive function. However, specific roles for neurones and gonadotrophs have been revealed under conditions of hyperinsulinaemia and by ablation of insulin and leptin receptors. The collective picture is one of multiple insulin-responsive inputs to gonadotrophin releasing hormone neurones, with astrocytes being the most important player.


[Early surgical rehabilitation due to modified exenteration technique].
Orbital exenteration is a life intruding surgical procedure with severe functional, aesthetic and psychological consequences. Apart from the correct tumor treatment, early aesthetic and psychosocial rehabilitation is crucial for the well-being of the patient. We discuss reasons leading to exenteration and present new surgical techniques. Local flaps in the anterior socket improve wound healing allowing early placement of the prosthesis and therefore faster social rehabilitation of the patient. Between 2007 and 2011 seven patients with malignant orbital tumors (1 × plasmocytoma, 1 × melanoma, 1 × sarcoma, 1 × squamous cell carcinoma and 3 × basal cell carcinoma) received a radical orbital exenteration at the Department of Ophthalmology of the Zurich University Hospital. The medical histories were evaluated according to reasons for exenteration, surgical techniques and postoperative follow-up. Reconstruction of the anterior socket border succeeded using local flaps (Mustardé, Glabella and combined with further modified pedicled local full thickness skin flaps). The central defects were covered with split skin graft from the thigh. Three weeks after surgery the anterior border of the socket was completely healed without problems by local flaps with good blood supply. This allowed the early prosthetic fitting and wearing as well as quick social rehabilitation of the patient. The use of local flaps improves wound healing even in anticoagulated patients. This reduces the time of hospitalization and rehabilitation, and allows an early, satisfactory, social reintegration of the patient.


Glycerol lidocaine eardrops for the treatment of acute abacterial otitis externa.
Inflammations of the external auditory canal number among the most frequently occurring ear-nose-throat diseases. For local treatment, substances from various groups of active ingredients are used as combinations and as single-agent drugs, e.g. antibiotics, glucocorticoids or analgesics [1]. In the case of acute otitis externa, treatment measures focus on the reduction of pain and swelling. The study described here investigates the efficacy and safety of glycerol lidocaine eardrops for the treatment of acute abacterial otitis externa (CAS No. for glycerol: 56-81-5, lidocaine-HCl: 73-78-9). In this double-blind, three-arm study, 105 patients diagnosed with acute abacterial otitis externa were included and randomized to receive either glycerol eardrops, glycerol eardrops with 0.5% lidocaine, or glycerol eardrops with 2% lidocaine for seven days. The primary outcome parameter was the change of the five typical clinical symptoms, earache, itching, otorrhea, hearing impairment, and "clogged ear" at Visit 2 (Day 7) based on the initial examination on Day 0. Both therapy groups treated with a combination of glycerol and lidocaine exhibited definite improvement in overall symptoms after seven days. This improvement differed from the mild reduction of symptoms under treatment with glycerol eardrops alone. Overall improvement of symptoms, expressed by the area under the curve of the baseline-adjusted symptom sum score, yielded a mean value of 10.95 (standard deviation 27.4) for the morning survey of the groups receiving eardrops containing only glycerol; in comparison, for eardrops containing glycerol and 2% lidocaine it was 15.71 (+/- 23.6) and for glycerol with 0.5% lidocaine, 23.16 (+/- 19.4). No severe adverse events occurred. Five adverse events were documented during the clinical investigation, none of which was considered by the investigators to be related to the study medication. Local therapy with glycerol lidocaine eardrops is a safe, and cost-effective treatment for the widely spread clinical picture of acute abacterial otitis externa. The advantage regarding efficacy of this combination compared with glycerol eardrops must be demonstrated in an adequately powered clinical trial.


Annotated list of the assassin bugs (Heteroptera: Reduviidae) of Belize, with the description of two new species.
Fifty-one species of Reduviidae (Hemiptera: Heteroptera) are recorded from Belize; literature citations are provided where relevant, and specimen data are included for examined material. Thirteen previously-described species are reported from Belize for the first time, ten of which represent new generic records: Eupheno histrionicus Stål, 1862 (Cetherinae); Ghinallelia signoreti (Dohrn, 1860) (Emesinae); Rasahus albomaculatus (Mayr, 1865) (Peiratinae); Leogorrus interruptus Champion, 1899; Microlestria laevis Champion, 1899; Nalata quadrituberculata Champion, 1899; Nalata setulosa Stål, 1862; Pseudozelurus superbus (Champion, 1899); Zelurus spinidorsis (Gray, 1832) (all Reduviinae); Oncerotrachelus conformis Uhler, 1894; Saica fuscipes Stål, 1862 (both Saicinae); Gnathobleda litigiosa Stål, 1862; and Stenopoda wygodzinskyi Giacchi, 1969 (both Stenopodainae). Among the ten subfamilies reported, Belizean records for one subfamily, Saicinae, are reported for the first time. Accompanying the checklist are the descriptions of Castolus omega Swanson sp. nov. (Harpactorinae) and Pygolampis aptena Swanson sp. nov. (Stenopodainae).


Circuit-tunable sub-wavelength THz resonators: hybridizing optical cavities and loop antennas.
We demonstrate subwavelength electromagnetic resonators operating in the THz spectral range, whose spectral properties and spatial/angular patterns can be engineered in a similar way to an electronic circuit. We discuss the device concept, and we experimentally study the tuning of the resonant frequency as a function of variable capacitances and inductances. We then elucidate the optical coupling properties. The radiation pattern, obtained by angle-resolved reflectance, reveals that the system mainly couples to the outside world via a magnetic dipolar interaction.


Estrogens and development.
The normal development of the genital organs of mammals, including humans, is under hormonal control. A role for the female sex hormone estrogen in this process is still unclear. However, exposure of experimental animals or humans to the potent exogenous estrogen, diethylstilbestrol (DES), results in persistent differentiation effects. Since many chemicals in the environment are weakly estrogenic, the possibility of hormonally altered differentiation must be considered.


Changing the future of health professions: embedding interprofessional education within an academic health center.
Institutions are increasingly considering interprofessional education (IPE) as a means to improve health care and reduce medical errors in the United States. Effective implementation of IPE within health professions education requires a strategic institutional approach to ensure longevity and sustainability. In 2007, the Medical University of South Carolina (MUSC) established Creating Collaborative Care (C), an IPE initiative that takes a multifaceted approach to weaving interprofessional collaborative experiences throughout MUSC's culture to prepare students to participate in interprofessional, collaborative health care and research settings.In this article, the authors describe C's guiding conceptual foundation and student learning goals. They present its implementation framework to illustrate how C is embedded within the institutional culture. It is housed in the provost's office, and an overarching implementation committee functions as a central coordinating group. Faculty members develop and implement C activities across professions by contributing to four collaborating domains-curricular, extracurricular, faculty development, and health care simulation-each of which captures an IPE component. The authors provide examples of IPE activities developed by each domain to illustrate the breadth of IPE at MUSC. The authors believe that MUSC's efforts, including the conceptual foundation and implementation framework, can be generalized to other institutions intent on developing IPE within their organizational cultures.


[Treatment of colorectal cancer--hepatic metastases].
The aim of this study was to evaluate the effect of the local therapy for colorectal liver metastases on overall survival. Seventy-two patients who had resected liver metastases from colorectal cancer during the period from 1982 to 2001 were evaluated for survival. There was no significant difference in overall survival by either surgical method for colorectal liver metastases or postoperative arterial infusion chemotherapy. However, the 5-year survival rate of resected metachronous liver metastases with postoperative arterial infusion chemotherapy was 44.9%, and that for patients with no extra hepatic metastases was 57.4%. Patients who have metachronous liver metastases from colorectal cancer should therefore be considered for postoperative arterial infusion chemotherapy. It is necessary to improve the outcome for cases that have extra hepatic metastases.


Vitamin D and cardiovascular disease.
Vitamin D participates in numerous physiologic and pathologic processes. Most tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator of gene expression. Approximately 1 billion people worldwide have insufficient levels of vitamin D. Deficiency has been associated with many chronic diseases, including cardiovascular disease (CVD), which is the leading cause of death in both men and women. A relationship between vitamin D and CVD is implicated; however studies show conflicting data. Epidemiologic evidence and observational studies demonstrate an association between vitamin D deficiency and CVD; however, this is not substantiated by randomized controlled trials (RCTs). Many questions remain unanswered, but growing evidence supports a beneficial role of vitamin D on cardiovascular health. Key teaching points: • Vitamin D influences many cellular functions. • A global pandemic of vitamin D deficiency exists. • Epidemiologic data and observational studies suggest that vitamin D deficiency may increase cardiovascular risk. • RCTs show no significant relationship (however, studies have significant limitations). • The association between vitamin D status and CVD is uncertain, but low vitamin D levels may be an independent and modifiable CV risk factor.


Pharmaceutical and biological properties of poly(amino acid)/DNA polyplexes.
Physicochemical properties of polyplexes formed between pRSVlacZ and poly(amino acid)s were investigated as a paradigm of more complex, synthetic virus-like, DNA delivery systems, that are of interest to many gene delivery laboratories. We observed the interaction between polymer and DNA using ethidium exclusion, and determined the size distributions and the zeta potentials of polyplexes. We correlated these properties with their fundamental interactions with cultured B16 murine melanoma cells, and the resulting efficiency of transfection. A variety of poly(amino acid)s each condensed DNA to produce particles with mean hydrodynamic diameters of approximately 100 nm (a typical span of a population was 80-120nm). Poly(amino acid) polyplexes were unstable in electrolyte solutions such as cell culture media. The apparent particle size increased in electrolyte, depending on the charge ratio, to diameters up to 700 nm. This was thought to be due to aggregation, since neutral particles were most sensitive. When the charge ratio (+/-) exceeded unity polyplexes had positive zeta potentials (which peaked at approximately +30 mV), bound non-specifically to cells, were internalised and in the presence of an endosomolytic agent were able to transfect cells. Though all cationic poly(amino acid)s investigated formed polyplexes with similar physical properties, their biological properties were significantly different. Polyplexes prepared with poly-L-ornithine were the most effective transfection agents, but poly(lys-co-ala, 1: 1) systems appeared to be inactive. This may reflect the differences in uncoupling of DNA and polymer, which is expected to be necessary for passage through the nuclear pore. Uncoupling of polycation and DNA was investigated by exposing the complexes to dextran sulphate. Release of DNA was detected by increased fluorescence at 600 nm in the presence of ethidium. Release of DNA was incomplete from polyplexes formed with high molecular weight polylysine. This may explain the lower levels of transfection observed with high molecular weight polylysine. The significance of these observations for design of advanced non-viral gene delivery systems is discussed.


Kin or self-recognition? Colonial fusibility of the bryozoan Celleporella hyalina.
We estimated fusion frequency with respect to coancestry in the bryozoan Celleporella hyalina, whose briefly planktonic sexually produced larvae settle on algal substrata and proceed to form encrusting colonies by iterative budding. Frequency of fusion between paired colonies growing on an artificial substratum was positively correlated with coefficient of relatedness, with allorecognition ability increasing during the early stages of colonial growth after larval settlement. Parents repressed the growth of F1 progeny with which they had fused. The results are concordant with the Feldgarden-Yund model of selection for self-recognition, which regards fusion with kin as an inevitable source of error whose cost diminishes with increasing relatedness. Contrary to fusion compatibility, gametic compatibility is negatively correlated with coancestry, indicating a need for further research on the possibility of common or linked genetic control that has opposite effect at somatic and gametic levels.


Spatially controlled synthesis of silver nanoparticles and nanowires by photosensitized reduction.
The present paper reports on the spatially controlled synthesis of silver nanoparticles (NPs) and silver nanowires by photosensitized reduction. In a first approach, direct photogeneration of silver NPs at the end of an optical fiber was carried out. Control of both size and density of silver NPs was possible by changing the photonic conditions. In a further development, a photochemically assisted procedure allowing silver to be deposited at the surface of a polymer microtip was implemented. Finally, polymer tips terminated by silver nanowires were fabricated by simultaneous photopolymerization and silver photoreduction. The silver NPs were characterized by UV-visible spectroscopy and scanning electron microscopy.


[Cerebral infarction disclosing neurocysticercosis].
An ischaemic stroke related to neurocysticercosis observed in the Paris neighbourhood is reported. A 32-year-old man originating from Cape Verde presented a left lacunar stroke. CT scan showed multiple areas of calcifications and a left capsulostriatal lucency. Gadolinium enhanced MRI disclosed significant abnormalities surrounding the left middle cerebral artery in the sylvian fissure. The titers of anticysticercian antibodies were highly positive in the serum and the CSF. The investigations in search of another cause of the stroke were negative. The outcome was good after a treatment associating albendazole and methylprednisolone. The increasingly recognized links between neurocysticercosis and stroke, especially in endemic areas are reviewed. Neurocysticercosis is an exceptional cause of ischaemic stroke in non endemic areas. In non-endemic areas, this cause of stroke has to be systematically suspected in patients coming from endemic areas. The diagnosis is based upon MRI, CT scanner and serologic tests. Treatment requires anti-parasitic drugs. The role of the corticosteroids is discussed.


One-year retrospective clinical evaluation of hybrid composite restorations placed in United Kingdom general practices.
The purpose of this study was to assess Pertac II restorations placed in general dental practice. A total of 86 restorations (14 Class I, 10 Class II, 17 Class III, 5 Class IV, and 40 Class V) using a hybrid composite material (Pertac II) placed in 56 patients (mean age, 39 years) in 5 dental practices in the United Kingdom were assessed after 1 year by a trained evaluator and the dental practitioner who had placed the restoration. All the restorations were assessed for anatomic form, marginal adaptation, surface roughness, sensitivity or discomfort, gingival condition, and the presence or absence of secondary caries. Thirty-five (43%) restorations were placed in load-bearing situations, 9% of which were assessed as being in "heavy" occlusion. Five (6%) of the restorations were lost (all Class V restorations), 4 from premolars and 1 from a molar. Four were in wedge-shaped cavities and 1 small restoration was actually dislodged during examination. The remaining 81 (94%) restorations were found to be intact, with no secondary caries detected. A high percentage of optimal scores were recorded for both anatomic form and surface roughness. It is concluded that the evaluation demonstrated satisfactory clinical performance of Pertac II restorations after 1 year of clinical service in the wide variety of clinical situations seen in general dental practice. However, the potential for failure of hybrid composite materials in Class V situations appears high. It may be argued that clinicians who wish to use a resin-based material in a Class V situation should use a compomer or microfilled composite.


Peptide conjugation at the 5'-end of oligodeoxynucleotides abrogates toll-like receptor 9-mediated immune stimulatory activity.
Bacterial and synthetic DNA containing unmethylated CpG motifs act as ligands of Toll-like receptor 9 (TLR9). Our earlier studies showed that 5'-accessibility of synthetic oligodeoxynucleotides containing CpG motif (ODN) is required for TLR9-mediated immune stimulatory activity. Blocking the 5'-end of ODN through conjugation to a variety of moieties reduces immune stimulatory activity (Bioconjugate Chem. 2002, 13, 966-974). In the present study, we conjugated a model peptide, a 28-amino-acid-long beta-amyloid peptide, to either the 5'- or the 3'-end of an ODN via C3 and C6 alkyl linkers. We compared the immune stimulatory activity of the resulting conjugates with that of a parent ODN without conjugation in TLR9-transfected cells, mouse spleen cell cultures, and in vivo in mice. ODN with the peptide conjugated at the 3'-end via C3 and C6 linkers had immune stimulatory activity similar to that of the parent ODN in both in vitro and in vivo in mice. On the contrary, conjugation of peptide at the 5'-end of the ODN significantly abrogated immune stimulatory activity. In conclusion, the results presented here demonstrate that peptide/protein conjugation to ODN is optimal at the 3'-end with either C3 or C6 linker and conjugation at the 5'-end leads to significant loss of TLR9-mediated immune stimulation.


Interplay between epigenetics & cancer metabolism.
Nutrient utilization is dramatically altered when cells receive signals to proliferate. Characteristic metabolic changes enable cells to meet the large biosynthetic demands associated with cell growth and division. Changes in rate-limiting glycolytic enzymes redirect metabolism to support growth and proliferation. Metabolic reprogramming in cancer is controlled largely by oncogenic activation of signal transduction pathways and transcription factors. Although less well understood, epigenetic mechanisms may seem to contribute to the regulation of metabolic gene expression in cancer. Reciprocally, accumulating evidence suggests that metabolic alterations may affect the epigenome. Understanding the relation between metabolism and epigenetics in cancer cells may open new avenues for anti-cancer strategies. In multi-cellular systems, molecular signals promoting cell growth and proliferation mediate the switch between catabolism and anabolism. Both normal proliferating and cancer cells must achieve high levels of macromolecular biosynthesis to provide the raw materials needed to produce new daughter cells. From a therapeutic view point, it is of great interest to determine metabolic differences that exist between normal proliferating cells and cancer cells. Cancer cells also exhibit significant alterations in the epigenome. Recent data indicate that cellular metabolism and epigenetic phenomenon are engaged in crosstalk. Considering current efforts to target both cancer metabolism and epigenetics, an understanding of the relationship between these two key features is of paramount importance. Here we discuss the role of cellular metabolism in regulation of the epigenome. Moreover, we discuss how epigenetic changes may contribute to establish cancer-specific metabolic features.


Oxytocin requirements at elective cesarean delivery: a dose-finding study.
Oxytocin is frequently used by intravenous bolus and infusion to minimize blood loss and prevent postpartum hemorrhage at cesarean delivery. Current dosing regimens are arbitrary whereas large doses may pose a serious risk to the mother. The purpose of this study was to estimate the minimum effective intravenous bolus dose of oxytocin (ED90) required for adequate uterine contraction at elective cesarean in nonlaboring women. A randomized, single-blinded study was undertaken in 40 healthy term pregnant women presenting for elective cesarean under spinal anesthesia. Oxytocin was administered by bolus according to a biased coin up-and-down sequential allocation scheme with increments or decrements of 0.5 IU. Uterine contraction was assessed by the obstetrician, who was blinded to the dose of oxytocin, as either satisfactory or unsatisfactory. After achieving sustained uterine contraction, an infusion of 40 mU/min of oxytocin was started. Oxytocin-induced adverse effects and intraoperative complications were recorded and blood loss was estimated. Data were interpreted by parametric analysis based on logistic regression model and nonparametric analyses at 95% confidence intervals (CIs). The ED90 of oxytocin as determined by logistic regression model fitted to the data was estimated to be 0.35 IU (95% CI 0.18-0.52 IU), with nonparametric estimates of 97.1% (95% CI 84.9-99.8%) response rate at 0.5 IU, and 100% (95% CI 92.2-100%) at 1.0 IU. The estimated blood loss was 693 +/- 487 mL (mean +/- standard deviation). The bolus dose of oxytocin used at elective cesarean deliveries in nonlaboring women can be significantly reduced while maintaining effective uterine contraction. Alteration in practice will likely reduce the potential adverse effects of this drug when given in large bolus doses, but may require modification of the techniques to remove the placenta.


Use of blood in transurethral prostatectomy--routine or selective cross-matching?
In our series of 700 transurethral resections of the prostate 464 patients (66%) received no blood transfusions, while 121 patients (17%) received two or more units of blood. A significant relationship was demonstrated between the size of the prostate and the estimated blood loss, as well as between the presence of a preoperative urethral catheter and the blood loss.


ct-DNA Binding and Antibacterial Activity of Octahedral Titanium (IV) Heteroleptic (Benzoylacetone and Hydroxamic Acids) Complexes.
Five structurally related titanium (IV) heteroleptic complexes, [TiCl2(bzac)(L(1-4))] and [TiCl3(bzac)(HL(5))]; bzac = benzoylacetonate; L(1-5) = benzohydroximate (L(1)), salicylhydroximate (L(2)), acetohydroximate (L(3)), hydroxyurea (L(4)), and N-benzoyl-N-phenyl hydroxylamine (L(5)), were used for the assessment of their antibacterial activities against ten pathogenic bacterial strains. The titanium (IV) complexes (1-5) demonstrated significant level of antibacterial properties as measured using agar well diffusion method. UV-Vis absorption spectroscopic technique was applied, to get a better insight into the nature of binding between titanium (IV) complexes with calf thymus DNA (ct-DNA). On the basis of the results of UV-Vis absorption spectroscopy, the interaction between ct-DNA and the titanium (IV) complexes is likely to occur through the same mode. Results indicated that titanium (IV) complex can bind to calf thymus DNA (ct-DNA) via an intercalative mode. The intrinsic binding constant (K b ) was calculated by absorption spectra by using Benesi-Hildebrand equation. Further, Gibbs free energy was also calculated for all the complexes.


[Occult hepatic metastases from colorectal carcinoma: diagnostic and prognostic considerations].
Occult hepatic metastases (OHM) from colorectal cancer are those not evident to the surgeon at laparotomy. In this retrospective and "deductive" study the Authors evaluated the accuracy of hepatic CT scan and ultrasonography (US) to detect hepatic metastases. The CT and US accuracy rate was 78.4% and 79.8% respectively, and proved to be correlated to the intraoperative dimensions of the lesions. Sensitivity of these examinations, in the light of OHM identification, decreased to 69% and 69.2% respectively. This study shows that hepatic US and CT scan are not sufficient to identify OHM; the attempt to reduce the frequency of OHM by means of intraoperative ultrasonography could allow to obtain a more careful stadiation and prognosis of these neoplasms with possible therapeutic advantages.


5000 h Multi-Factor Accelerated Aging Test of FRP Made Transmission Tower: Characterization, Thermal Decomposition and Reaction Kinetics Study.
Three kinds of fiber reinforced plastic (FRP) composites, including modified polyurethane resin (LGD), epoxy resin (E44) and modified unsaturated polyester resin (D33) glass-fiber reinforced plastics, were subjected to a 5000 h multi-factor accelerated aging test according to the power industry standard. To examine aging resistance and thermal stability of transmission towers made by these three composites, relevant bending properties, thermogravimetric analysis (TGA) and derivative thermogravimetry (DTG), activation energy, as well as microscopic morphology were revealed. The results showed that for these composites, bending modulus retention rates were higher than 94% under the aging test and that of the LGD was highest. Additionally, the onset degradation temperature, temperature at maximum rate of weight loss and T5% reduced at 5000 h, with D33 having highest value and lowest decline rate. The activation energy was calculated with the Bagchi, Coats-Redfern and Broido method, respectively. Although the activation energy of all composites decreased after test, the D33, LGD materials had the highest activation energy which enjoys slight decline. Analysis of the whole experimental results suggested that D33 and LGD composites have good aging resistance, whose basic performance could still perform well after 5000 h aging test, so they can be used to composite towers and applied to engineering practice.


[Problems and solutions in giving an expert evaluation].
According to the law for the prevention of cruelty to animals, the officially employed veterinarians are the experts per se. All administrative legal steps are based on their reports. Such reports are also of major significance at court hearings. However, veterinary colleagues working in private practices or clinics are often requested to submit an expert evaluation in cases of cruelty to animals. The problems which occur in putting together an expert's report are often based on a lack of knowledge about the clear structure of such a report (preliminary details, description of the situation as found, assessments of results, evaluation of findings, justification). The situation is made more complicated by the two different languages of lawyers (that of administrative officials, advocates of district courts and higher district courts or public prosecutors) and of veterinarians. A detailed description and a clear assessment together with a detailed justification of the concluding findings are absolutely essential. By providing examples of the correct way to write an expert's report, both the problems and solutions to improve the situation can be pointed out. This will be of the utmost importance in the future when quality management of animal rights is introduced. Specific training should be introduced during studies, in training courses for district examinations and in practical, further education. In addition, the range of problems caused by the constantly rising number of expert's reports made as a favour should also be considered.


Tolerogenic DNA vaccine for prevention of autoimmune ovarian disease.
DNA vaccines have been widely used to induce immune responses against molecular targets. In this study, we explored the possibility of using DNA vaccine combined with the immunosuppressant FK506 (tacrolimus) to antigen-specifically suppress unwanted immune responses and prevent autoimmune ovarian disease. To that end, we immunized C57BL/6 mice with a DNA vaccine encoding mouse zona pellucida 3 (ZP3) together with FK506. The immunization induced ZP3-specific CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg), which suppressed the induction of ZP3-specific delayed-type hypersensitivity in the animals. Significantly, the immunization also protected the animals from experimentally induced autoimmune ovarian disease. These results suggest that DNA vaccination in the presence of FK506 may be used to induce Treg cells and prevent AOD.


Utilizing the Promise of Omadacycline in a Resistant, Non-tubercular Mycobacterial Pulmonary Infection.
The non-tubercular mycobacterium, Mycobacterium abscessus (M. abscessus), is a resistant, opportunistic pathogen that causes lung infections that are not curable, but which can be controlled with appropriate antibiotic regimens. A new broad-spectrum tetracycline analog called omadacycline was approved in 2018 in the United States for the treatment of bacterial, community-acquired pneumonia and acute skin infections. We discuss a case to assess the effect of this novel antibiotic in the management of a nefariously resistant M. abscessus infection. Our patient had underlying chronic bronchiectasis and a long-standing M.abscessus infection, along with numerous drug allergies and previously failed antibiotic regimens. All of these factors entailed a disease process that was difficult to manage and a worsening morbidity. The utilization of omadacycline in this case addressed a multitude of problems by improving ease of administration and circumventing the patient's allergic reaction to antibiotics; on follow-up, the patient demonstrated an improved clinical status including well-controlled symptoms and weight gain.


Configuration of Multifunctional Polyimide/Graphene/Fe3O4 Hybrid Aerogel-Based Phase-Change Composite Films for Electromagnetic and Infrared Bi-Stealth.
Electromagnetic (EM) and infrared (IR) stealth play an important role in the development of military technology and the defense industry. This study focused on developing a new type of multifunctional composite film based on polyimide (PI)/graphene/Fe3O4 hybrid aerogel and polyethylene glycol (PEG) as a phase change material (PCM) for EM and IR bi-stealth applications. The composite films were successfully fabricated by constructing a series of PI-based hybrid aerogels containing different contents of graphene nanosheets and Fe3O4 nanoparticles through prepolymerizaton, film casting, freeze-drying, and thermal imidization, followed by loading molten PEG through vacuum impregnation. The construction of PI/graphene/Fe3O4 hybrid aerogel films provides a robust, flexible, and microwave-absorption-functionalized support material for PEG. The resultant multifunctional composite films not only exhibit high microwave absorption effectiveness across a broad frequency range, but also show a good ability to implement thermal management and temperature regulation under a high latent-heat capacity of over 158 J/g. Most of all, the multifunctional composite films present a wideband absorption capability at 7.0-16.5 GHz and a minimum reflection loss of -38.5 dB. This results in excellent EM and IR bi-stealth performance through the effective wideband microwave absorption of graphene/Fe3O4 component and the thermal buffer of PEG. This study offers a new strategy for the design and development of high-performance and lightweight EM-IR bi-stealth materials to meet the requirement of stealth and camouflage applications in military equipment and defense engineering.


In the previous cytogenetic study of new human stem cell line 4BL at the 205th passage we observed the ploidy of chromosomal set and regular aberrations. To investigate the nature of monosomy of certain chromosomes the array CGH and FISH analyses have been used. The aberrations of chromosomes have been identified in all the cases of monosomies previously revealed by G-banding. The largest changes of the DNA balance have been detected in the chromosomes 2, 4, 10, 13 and 17. The probable cause of the monosomies of chromosomes 4, 10, 13 and 17 is massive loss of the genetic material. The monosomy of the second chromosome pair is caused by significant transformation one of the homologs in a type of numerous duplications and formation of der(2)t(2;?)(q21;?). Due to application of array CGH the regions of the structural aberrations of the chromosomes 2, 4, 10, 13 and 17 have been concretized, what permitted to perform their clarifying identification by multicolored FISH method. The results obtained by us confirm the hypothesis about coordinated appearance of the deletions and duplications and their stabilization impact on the transformed chromosomes.


Correction versus palliation of congenital heart diseases in the first year of life.
In the period 1971-1981 220 children below 1 year of age have been operated upon in our Hospital for Congenital Heart Diseases (CHD). Among them, 125 children were selected, in whom, because of the type of CHD present, either a palliation or a correction could have been chosen as the surgical approach. The first three common malformation treated are presented.


Analysis of amino acids, hydroxy acids, and amines in CR chondrites.
The abundances, relative distributions, and enantiomeric and isotopic compositions of amines, amino acids, and hydroxy acids in Miller Range (MIL) 090001 and MIL 090657 meteorites were determined. Chiral distributions and isotopic compositions confirmed that most of the compounds detected were indigenous to the meteorites and not the result of terrestrial contamination. Combined with data in the literature, suites of these compounds have now been analyzed in a set of six CR chondrites, spanning aqueous alteration types 2.0-2.8. Amino acid abundances ranged from 17 to 3300 nmol g-1 across the six CRs; hydroxy acid abundances ranged from 180 to 1800 nmol g-1; and amine abundances ranged from 40 to 2100 nmol g-1. For amino acids and amines, the weakly altered chondrites contained the highest abundances, whereas hydroxy acids were most abundant in the more altered CR2.0 chondrite. Because water contents in the meteorites are orders of magnitude greater than soluble organics, synthesis of hydroxy acids, which requires water, may be less affected by aqueous alteration than amines and amino acids that require nitrogen-bearing precursors. Two chiral amino acids that were plausibly extraterrestrial in origin were present with slight enantiomeric excesses: L-isovaline (~10% excess) and D-β-amino-n-butyric acid (~9% excess); further studies are needed to verify that the chiral excess in the latter compound is truly extraterrestrial in origin. The isotopic compositions of compounds reported here did not reveal definitive links between the different compound classes such as common synthetic precursors, but will provide a framework for further future in-depth analyses.


Immunohistochemical characterization of T-lymphocytes subsets in Egyptian hepatic schistosomiasis.
Liver biopsies from 20 schistosomal patients in the compensated stage were studied by immunoalkaline phosphatase technique for the relative distribution of T-cell subpopulations. T-cell subsets were defined for OKT3 (+) (pan T-lymphocytes), OKT4 (+) (helper-inducer), and OKT8 (+) (suppressor-cytotoxic) cell by using mouse hybridoma monoclonal antibodies. Sections showed marked pan T-lymphocytic infiltration predominantly in the portal tract within liver lobules and in the granulomatous lesions. Marked relative increment of suppressor/cytotoxic OKT8 (+) lymphocytes over the helper/inducer OKT4 (+) were observed. Alkaline phosphatase activity showed inverse significant correlation with OKT3 (+) and OKT8 (+) % and a direct significant correlation with OKT4 (+) % lymphocytes. This may suggest that suppressor cytotoxic OKT8 lymphocytes may be responsible for the modulation of the granulomata and stabilization of the morbidity state.


[Lung carcinoma. An unusual case of survival].
Lung cancer incidence is continuously increasing over the world, despite significant advances in both the diagnostic and therapeutic fields. At the diagnosis, more than 2/3 of patients present a locally advanced disease associated with a 5-year survival of less than 35%, or with distant metastases associated with no long-time survival. Chemotherapy with cisplatin remains a well established option in the treatment of lung cancer, as confirmed by recent meta-analyses, and its action seems strengthened by the introduction of new agents (taxans, gemcitabine, vinorelbine, topotecan, and others), that are giving promising results for a better control of this disease.


Psychosis and enuresis during disulfiram therapy.
Disulfiram is the drug that is commonly prescribed for the treatment of alcohol dependence syndrome, and transient functional psychosis has been reported as one of its side-effects. Enuresis is another rare adverse effect reported. This report discusses a case of acute psychosis and enuresis in a patient on disulfiram who had ingested alcohol.


Myc regulates embryonic vascular permeability and remodeling.
Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic endothelial cells using a tetracycline-regulated system. Endothelial Myc overexpression resulted in severe defects in the embryonic vascular system. Myc-expressing embryos undergo widespread edema formation and multiple hemorrhagic lesions. They die between embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole-mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc-expressing embryos is characterized by a reduction in vessel branching, which occurs despite upregulation of the proangiogenic factors vascular endothelial growth factor-A and angiopoietin-2. Thus, the net outcome of an excess of vascular endothelial growth factor-A and angiopoietin-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity.


Periosteal Fixation Procedures in the Management of Incomitant Strabismus.
Managing a case of incomitant strabismus from nerve palsy or extraocular muscle loss is a major challenge. Among possible management options are globe or extraocular muscle fixation to the orbital wall coupled with weakening or strengthening of the relevant antagonist. Extraocular muscle fixation to the orbital wall can also be used in cases of abnormal synkinesis to eliminate the abnormal eye movements of a misfiring extraocular muscle, which thereby allows the use of standard paralytic strabismus surgery techniques. This review article summarizes indications and techniques of periosteal fixation procedures for incomitant strabismus.


Implicit and explicit memory for novel visual objects: structure and function.
Six experiments compared the effects of structural and functional encoding tasks on implicit and explicit memory for novel objects. Implicit memory was assessed with a possible-impossible object decision test, and explicit memory was assessed with a yes-no recognition test. Results revealed that recognition memory was higher after functional than after structural encoding tasks, whereas priming effects on the object decision test were unaffected by the same manipulations. The priming effects that were observed after functional encoding tasks could be attributed to structural analyses that are carried out in the course of making judgments about functional properties of novel objects. Results are consistent with the hypothesis that implicit memory for novel objects depends on a presemantic structural description system that can operate independently of episodic memory.


Paving the Way to Personalized Genomic Medicine: Steps to Successful Implementation.
Over the last decade there has been vast interest in and focus on the implementation of personalized genomic medicine. Although there is general agreement that personalized genomic medicine involves utilizing genome technology to assess individual risk and ensure the delivery of the "right treatment, for the right patient, at the right time," different categories of stakeholders focus on different aspects of personalized genomic medicine and operationalize it in diverse ways. In order to move toward a clearer, more holistic understanding of the concept, this article begins by identifying and defining three major elements of personalized genomic medicine commonly discussed by stakeholders: molecular medicine, pharmacogenomics, and health information technology. The integration of these three elements has the potential to improve health and reduce health care costs, but it also raises many challenges. This article endeavors to address these challenges by identifying five strategic areas that will require significant investment for the successful integration of personalized genomics into clinical care: (1) health technology assessment; (2) health outcomes research; (3) education (of both health professionals and the public); (4) communication among stakeholders; and (5) the development of best practices and guidelines. While different countries and global regions display marked heterogeneity in funding of health care in the form of public, private, or blended payor systems, previous analyses of personalized genomic medicine and attendant technological innovations have been performed without due attention to this complexity. Hence, this article focuses on personalized genomic medicine in the United States as a model case study wherein a significant portion of health care payors represent private, nongovernment resources. Lessons learned from the present analysis of personalized genomic medicine could usefully inform health care systems in other global regions where payment for personalized genomic medicine will be enabled through private or hybrid public-private funding systems.


ANGPTL6 Genetic Variants Are an Underlying Cause of Familial Intracranial Aneurysms.
To understand the role of the angiopoietin-like 6 gene (ANGPTL6) in intracranial aneurysms (IAs), we investigated its role in a large cohort of familial IAs. Individuals with family history of IA were recruited to the Genetic and Observational Subarachnoid Haemorrhage (GOSH) study. The ANGPTL6 gene was sequenced using Sanger sequencing. Identified genetic variants were compared to a control population. We found 6 rare ANGPTL6 genetic variants in 9/275 individuals with a family history of IA (3.3%) (5 missense mutations and 1 nonsense mutation leading to a premature stop codon), none present in controls. One of these had been previously reported: c.392A>T (p.Glu131Val) on exon 2; another was very close: c.332G>A (p.Arg111His). Two further genetic variants lie within the fibrinogen-like domain of the ANGPTL6 gene, which may influence function or level of the ANGPTL6 protein. The last 2 missense mutations lie within the coiled-coil domain of the ANGPTL6 protein. All genetic variants were well conserved across species. ANGPTL6 genetic variants are an important cause of IA. Defective or lack of ANGPTL6 protein is therefore an important factor in blood vessel proliferation leading to IA; dysfunction of this protein is likely to cause abnormal proliferation or weakness of vessel walls. With these data, not only do we emphasize the importance of screening familial IA cases for ANGPTL6 and other genes involved in IA, but also highlight the ANGPTL6 pathway as a potential therapeutic target. This is a Class III study showing some specificity of presence of the ANGPTL6 gene variant as a marker of familial intracranial aneurysms in a small subset of individuals with familial aneurysms.


Interleukin-6 in synovial fluid and HLA-DR expression in synovium from patients with temporomandibular disorders.
Interleukin-6-dependent mouse hybridoma cell line KD83 was used to test the biologic activity of interleukin-6 in synovial fluid from 37 patients with temporomandibular disorders. The results showed that the interleukin-6 level was greater than 100 U/mL in 13 of 18 patients with degenerative joint disease and in five of 12 patients with temporomandibular disc displacement. However, the interleukin-6 level was less than 100 U/mL (range, 20 to 75 U/mL) in all patients with masticatory muscle disorder. It has been found that degenerative joint disease tends to have acute and chronic stages, and interleukin-6 activity was probably related to the acute stage in the patients. Histologic studies of the synovium from seven patients with degenerative joint disease showed a variable degree of hyperplasia of the synovial lining cells and chronic inflammation in five of eight specimens. Immunostaining studies clearly showed the presence of significantly more HLA-DR-expressing cells (human leukocyte antigen-D-related) in synovium. Although it is unlikely that immune responses play an important primary role in initiating synovial inflammation and cartilage destruction, immune reactions may be one important factor in the maintenance and severity of some patients with temporomandibular disorders.


Preoperative tumor embolization.
We performed an embolization of tumors which we considered to need preoperative embolization, such as deep-seated tumors, or hypervascular tumors. We experienced 12 such cases in the two-year period from September 1996. Eight cases were meningiomas, one case was a hemangiopericytoma, one case was an angiofibroma and two cases were glomus tumors. As embolic material, we usually use estrogen-alcohol and polyvinyl acetate which soften the tumor. When a provacative test is either impossible or positive, the distal induction of a microcatheter is impossible or a dangerous anastomosis is present, we select polyvinyl alchol particles (120 approximately 250mum) and liquid coils. We performed an embolization of a very hypervascular tumor, juvenile angiofibroma, by a direct tumor puncture, using a mixure of N-butylcyanoacrylate, lipiodol and tantalum powder. Angiography in all cases showed a reduction of the tumor stain. The embolic method should be selected based on a combination of such factors as the purpose of embolization, the identification of the feeding artery and the histological findings.


A sex difference in interference between identity and expression judgments with static but not dynamic faces.
Facial motion cues facilitate identity and expression processing (Pilz, Thornton, & Bülthoff, 2006). To explore this dynamic advantage, we used Garner's speeded classification task (Garner, 1976) to investigate whether adding dynamic cues alters the interactions between the processing of identity and expression. We also examined whether facial motion affected women and men differently, given that women show an advantage for several aspects of static face processing (McClure, 2000). Participants made speeded identity or expression judgments while the irrelevant cue was held constant or varied. Significant interference occurred with both tasks when static stimuli were used (as in Ganel & Goshen-Gottstein, 2004), but interference was minimal with dynamic displays. This suggests that adult viewers are either better able to selectively attend to relevant cues, or better able to integrate multiple facial cues, when viewing moving as opposed to static faces. These gains, however, come with a cost in processing time. Only women showed asymmetrical interference with static faces, with variations in identity affecting expression judgments more than the opposite. This finding may reflect sex differences in global-local processing biases (Godard & Fiori, 2012). Our findings stress the importance of using dynamic displays and of considering sex distributions when characterizing typical face processing mechanisms.


Research and dermatologic excellence.
Nearly everyone, even within our small specialty, has a slightly different idea, or bias, as to what constitutes research. We hear of clinical research and academic research and pharmaceutical research and descriptive research and cutting-edge research, but the distinctions often blur and are unimportant. What is important is that research of all kinds increases knowledge and adds information that improves patients' well-being. Perhaps we can agree with a general definition: Research is inquiry. In its simplest form, it may be nothing more than a literature review pertinent to an observation or interest. More often we think of systematic research (a progression starting with questions and ideas) moving forward to a hypothesis, then planning approaches and methods for experiments, all directed toward characterizing normal features and disease mechanisms to prevent and treat illness.


RIPK3 Contributes to Lyso-Gb3-Induced Podocyte Death.
Fabry disease is a lysosomal storage disease with an X-linked heritage caused by absent or decreased activity of lysosomal enzymes named alpha-galactosidase A (α-gal A). Among the various manifestations of Fabry disease, Fabry nephropathy significantly affects patients' morbidity and mortality. The cellular mechanisms of kidney damage have not been elusively described. Necroptosis is one of the programmed necrotic cell death pathways and is known to play many important roles in kidney injury. We investigated whether RIPK3, a protein phosphokinase with an important role in necroptosis, played a crucial role in the pathogenesis of Fabry nephropathy both in vitro and in vivo. The cell viability of podocytes decreased after lyso-Gb3 treatment in a dose-dependent manner, with increasing RIPK3 expression. Increased reactive oxygen species (ROS) generation after lyso-Gb3 treatment, which was alleviated by GSK'872 (a RIPK3 inhibitor), suggested a role of oxidative stress via a RIPK3-dependent pathway. Cytoskeleton rearrangement induced by lyso-Gb3 was normalized by the RIPK3 inhibitor. When mice were injected with lyso-Gb3, increased urine albuminuria, decreased podocyte counts in the glomeruli, and effaced foot processes were observed. Our results showed that lyso-Gb3 initiated albuminuria, a clinical manifestation of Fabry nephropathy, by podocyte loss and subsequent foot process effacement. These findings suggest a novel pathway in Fabry nephropathy.


Changes in the cupula after disruption of the membranous labyrinth.
Various changes were observed in the cupula, including shrinkage and enlarged volume, following the disruption of the membranous labyrinth. Cupular change after membranous labyrinth disruption may be a pathology of vestibular disorders. To observe the morphological changes of the cupula after disruption of the membranous labyrinth and to compare the cupular changes with changes in the compound action potential (CAP) of the ampullary nerve. A labyrinthine injury model was created by puncturing the membranous labyrinth of bullfrogs. The cupula was observed from 3 to 17 days after the membrane puncture. The CAP in response to mechanical endolymphatic flow was recorded from the ampullary nerve. The correlation between cupular change and CAP positivity was evaluated using the authors' scale. Various kinds of cupular changes including shrinkage were observed. Cupular change was more severe after a longer survival period. Large or elongated volume of the cupula was also observed, which was not observed in our previous study using gentamicin. The CAP could be recorded even when the cupular change was severe.


Additions to Hohenbuehelia (Basidiomycota, Pleurotaceae): two new species and notes on H.tristis from northern Thailand.
Two new species and a first geographical record of Hohenbuehelia are described from Thailand. Macroscopic and microscopic descriptions with photoplates, as well as a multigene phylogeny are provided. Hohenbueheliaflabelliformissp. nov. is recognised by large flabelliform basidiomata, densely villose yellowish-white pileus with white hairs near the point of attachment, basidiospores that mostly are ellipsoid in front view and phaseoliform in side view, the absence of cheilocystidia, and a trichoderm pileipellis. Hohenbuehelialageniformissp. nov. is characterised by fleshy basidiomata, velutinous pileus with whitish hairs near the point of attachment and the margin, elsewhere pale greyish-yellow and with only sparse white hairs, pale brown to light brown and mucilaginous context, subglobose basidiospores, lageniform cheilocystidia, an ixotrichoderm pileipellis, and the absence of pileoleptocystidia. Hohenbueheliatristis is characterised by small creamy-white, spathuliform basidiomata that are larger than the type subspecies, minutely pubescent pileus with tiny greyish hairs that disappear when mature, leaving the surface glutinous, faintly translucent and shiny, ellipsoid to sub-ellipsoid basidiospores, lecythiform to sublageniform cheilocystidia, and an ixotrichoderm pileipellis. Hohenbueheliatristis is recorded for Thailand for the first time. Based on the polymorphism observed in part of the nrLSU gene, the presence of two divergent lineages within H.tristis is discussed.


Adoptive transfer studies demonstrate that macrophages can induce proteinuria and mesangial cell proliferation.
Glomerular macrophage accumulation is a feature of proliferative human and experimental glomerulonephritis. However, our understanding of the role of macrophages in the induction of renal injury is based upon indirect evidence from depletion studies, most of which lack specificity for this cell type. Therefore, an adoptive transfer approach was used to directly assess the potential of macrophages to induce renal injury. Accelerated anti-glomerular basement membrane (anti-GBM) disease was induced in rats by immunization with sheep IgG (day -5), followed by administration of sheep anti-rat GBM serum (day 0), with animals killed on day 2. To facilitate the adoptive transfer studies, immunized animals were made leukopenic by cyclophosphamide (CyPh) given on day -2. Bone marrow-derived (BM) or NR8383 macrophages were transferred by tail vein injection 24 hours after injection of anti-GBM serum, with animals killed 3 or 24 hours after transfer. Pretreatment with CyPh prevented glomerular leukocyte accumulation and completely inhibited proteinuria, glomerular cell proliferation and hypercellularity in accelerated anti-GBM disease. Adoptive transfer led to significant glomerular accumulation of BM or NR8383 macrophages within 3 hours of injection, and this was still evident 24 hours later. Adoptive transfer of BM or NR8383 macrophages induced proteinuria (63 +/- 16 BM vs. 5 +/- 2 mg/24 h CyPh control; P < 0.001), glomerular cell proliferation (5.1 +/- 1.2 BM vs. 0.5 +/- 0.1 PCNA+ cells/gcs CyPh; P < 0.001) and glomerular hypercellularity (51.2 +/- 2.0 BM vs. 41.9 +/- 0.9 nuclei/gcs CyPh; P < 0.001). The degree of renal injury correlated with the number of transferred glomerular macrophages. Two-color immunostaining demonstrated that most glomerular proliferative cell nuclear antigen+ (PCNA+) proliferating cells were OX-7+ mesangial cells. CyPh treatment did not prevent up-regulation of glomerular intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression or an increase in urinary monocyte chemoattractant protein-1 (MCP-1) excretion. This study provides the first direct evidence that macrophages can induce renal injury in terms of proteinuria and mesangial cell proliferation.


Neurotoxicity of lead, methylmercury, and PCBs in relation to the Great Lakes.
There is ample evidence identifying lead, methylmercury, and polychlorinated biphenyls (PCBs) as neurotoxic agents. A large body of data on the neurotoxicity of lead, based on both epidemiologic studies in children and animal models of developmental exposure, reveals that body burdens of lead typical of people in industrialized environments produce behavioral impairment. Methylmercury was identified as a neurotoxicant in both adults and the developing organism based on episodes of human poisoning: these effects have been replicated and extended in animals. High-dose PCB exposure was recognized as a developmental toxicant as a result of several episodes of contamination of cooking oil. The threshold for PCB neurotoxicity in humans is less clear, although research in animals suggests that relatively low-level exposure produces behavioral impairment and other toxic effects. Tissue levels in fish below which human health would not be adversely affected were estimated for methylmercury and PCBs based on calculated reference doses (RfDs) and estimated fish intake. Present levels in fish tissue in the Great Lakes exceed these levels for both neurotoxicants. Great Lakes fish and water do not pose a particular hazard for increased lead intake. However, the fact that the present human body burden is in a range at which functional deficits are probable suggests that efforts should be made to eliminate point sources of lead contamination in the Great Lakes basin.


Application-Specific Adaptable Coatings for Sensors: Using a Single Polymer-Plasticizer Pair to Detect Aromatic Hydrocarbons, Mixtures, and Interferents in Water with Single Sensors and Arrays.
A relatively simple design procedure is presented for new, adaptable chemical sensor coatings made from a single polymer-plasticizer pair to detect single or a mixture of chemical compounds (e.g., BTEX, the small aromatic hydrocarbon family). Affinity between coating components and target analytes, expressed through Hansen solubility parameters and relative energy difference values, describes the sensitivity of the resultant coatings to each analyte. While analyte affinity is paramount for plasticizer selection, for the aqueous-phase sensing application described here, it must be traded off with the permanence in the host polymer, i.e., resistance to leaching into the ambient aqueous phase; deleterious effects including coating creep must also be minimized. By varying the polymer:plasticizer mixing ratio, the physical and chemical properties of the resultant coatings can be tuned across a range of sensing properties, in particular the differential response magnitude and rate, for multiple analytes. Together with the measurement of multiple sensor response parameters (relative sensitivity and response time constant) for each coating, this approach allows for identification and quantification of target analytes not previously separable using commercial off-the-shelf (COTS) polymer sensor coatings. Sensing results using a five-sensor array based on five different mixing ratios of a single plasticizer polymer pair (plasticizer: ditridecyl phthalate; polymer: polystyrene) demonstrate unique identification of mixtures of BTEX analytes, including differentiation of the chemical isomers ethylbenzene and total xylene (or "xylenes"), something not previously feasible for separation-free liquid-phase sensing with commercially available polymer coatings. Ultimately, the response of a single optimized sensor coating identified and quantified the components of various mixtures, including identification of likely interferents, using a customized estimation-theory-based multivariate signal-processing technique.


Fish Loss/Waste and Low-Value Fish Challenges: State of Art, Advances, and Perspectives.
The sustainability of fishery is a global challenge due to overfishing and reduced stocks all over the world; one of the leading factors of this threat is fish loss/waste. As a contribution to the global efforts towards a sustainable world, this review addresses the topic from different sides and proposes an overview of biorefinery approaches by discussing bioactive compounds that could be produced from fish loss (nitrogen compounds, lipids, minerals and pigments, and fish-based compounds such as chitosan). The second part of this review reports on the possibility of using loss or unwanted fish to design products for human consumption or for animal feeding, with a focus on economic criteria, consumers' segmentation, and some examples of products. The final focus is on Food and Agriculture Organization FAO guidelines as a roadmap for the future with respect to solving this threat by addressing the problem from different sides (technology, skills, market, policy, social and gender equity, and infrastructures).


Value of the application of the heart rate performance curve in sports.
The heart rate performance curve (HRPC) has been shown to be nonlinearly related to work load. This phenomenon has been used to determine a deflection point and to be related to the lactate anaerobic threshold. The original method was heavily criticized, and the method was challenged by several authors. However, some authors also demonstrated a high value for this method's application in various sports conditions. Unfortunately, the HRPC was shown to be not uniform and three different patterns were found. Basic investigations have shown a dependence of the HR-deflection on beta1-receptor sensitivity, which gave a plausible explanation of the phenomenon. Important details regarding the testing protocol and the method of turn point determination are given in this review. As a conclusion, we may state that based on numerous studies the method is plausible and valid to determine aerobic exercise performance in various laboratory ergometer and specific sports-related field conditions. Standard protocol conditions adjusted to the exercise performance level of subjects and a computer-supported determination of turn points are necessary to obtain reliable results. Large-scale investigations to validate the heart rate turn point with maximal lactate steady state are still needed. However, from the available literature, the application of this noninvasive method can be recommended to determine aerobic exercise performance in various sports. This noninvasive test is easy to perform repeatedly, which gives interesting possibilities for the monitoring of training adaptation in the short term, such as altitude training or specific taper forms.


Digoxin prophylaxis following coronary artery bypass surgery.
The effect of the postoperative administration of digoxin to patients undergoing coronary artery bypass surgery on the incidence of supraventricular arrhythmias was studied. Patients were randomly assigned to a control group (n = 51) or digoxin group (n = 47) on a prospective basis. Patient characteristics were similar in both groups, and no patients were receiving digoxin therapy preoperatively or other antiarrhythmic medications. All patients had normal systolic ejection fractions, renal function, and hepatic function. Eight patients (16%) in the control group developed postoperative arrhythmias while seven patients (15%) in the digoxin group developed supraventricular arrhythmias. This difference was not significant. Two patients in the digoxin group developed digoxin-induced arrhythmias, and two other patients experienced digoxin-related nausea and vomiting, which were resolved with discontinuation of the drug. The postoperative administration of digoxin to patients undergoing coronary artery bypass surgery had no effect on the incidence of supraventricular arrhythmias. The prophylactic use of digoxin therapy in this patient population is not recommended unless there is a history of arrhythmias responsive to digoxin therapy.


Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs.
A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-PAMPA Pampa) was validated using a Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-PAMPA were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for eight Biopharmaceutic Classification System (BCS) model drugs cited in the FDA guidance and another six drugs (acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-PAMPA. Apparent permeability (Papp) Franz-PAMPA values were correlated with fraction of dose absorbed in humans (Fa%) from the literature. Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-PAMPA performance. Mannitol and metoprolol Papp values across Franz-PAMPA were lower (3.20 × 10-7 and 1.61 × 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10-5 and 2.55 × 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-PAMPA method for use during the drug discovery process.