An online automatic sorting system for defective Ginseng Radix et Rhizoma Rubra using deep learning.
To establish a deep-learning architecture based on faster region-based convolutional neural networks (Faster R-CNN) algorithm for detection and sorting of red ginseng (Ginseng Radix et Rhizoma Rubra) with internal defects automatically on an online X-ray machine vision system. A Faster R-CNN based classifier was trained with around 20 000 samples with mean average precision value (mAP) of 0.95. A traditional image processing method based on feedforward neural network (FNN) obtained a bad performance with the accuracy, recall and specificity of 69.0%, 68.0%, and 70.0%, respectively. Therefore, the Faster R-CNN model was saved to evaluate the model performance on the defective red ginseng online sorting system. An independent set of 2 000 red ginsengs were used to validate the performance of the Faster R-CNN based online sorting system in three parallel tests, achieving accuracy of 95.8%, 95.2% and 96.2%, respectively. The overall results indicated that the proposed Faster R-CNN based classification model has great potential for non-destructive detection of red ginseng with internal defects.


Dynamic regulation of innate immunity by ubiquitin and ubiquitin-like proteins.
Protein post-translational modifications (PTMs) are central to the host innate immune regulations. Dynamically, PTMs fine-tune the spatial and temporary responses of immune- and non-immune-cells, in accordance with extracellular and intracellular stresses. Ubiquitin and ubiquitin-like proteins (Ubls) are emerging as the important multi-functional signals, controlling the activation, stability, affinity and location of many signaling proteins. Recent investigations, at the molecular-cellular-animal models, have shed new light on the versatility of the ubiquitin, SUMO and ISG15, for shaping the strength and duration of the innate immune responses. This review summarizes our current knowledge on the functions and regulatory mechanisms of the ubiquitin and Ubls in the innate immunity, the first line of host defense against microbial infection.


Hunteriasines A - D, tryptamine-derived alkaloids from Hunteria umbellata.
Four undescribed tryptamine-derived alkaloids, hunteriasines A - D, were isolated and identified from Hunteria umbellata (Apocynaceae), together with fifteen known indole alkaloids. The chemical structure and absolute configuration of hunteriasine A were determined by spectroscopic and X-ray crystallographic data analyses. Hunteriasine A, featuring with a unique scaffold comprised of tryptamine and an unprecedented "12-carbon unit" moiety, is a zwitterionic indole-derived and pyridinium-containing alkaloid. Hunteriasines B - D were identified by spectroscopic data analyses and theoretical calculations. A plausible biogenetic pathway for hunteriasines A and B was proposed. The lipopolysaccharide-stimulated mouse macrophage cell line J774A.1 cell-based bioactivity assays revealed that (+)-eburnamine, strictosidinic acid, and (S)-decarbomethoxydihydrogambirtannine enhance the release of interleukin-1β.


Managing frostbite in a South African patient.
This report focuses on a 23-year-old man of African-Caribbean origin who presented to a Burns unit with soft-tissue loss following a road traffic collision (RTC) in an extremely cold weather. Having been involved in the RTC, he walked from the scene to the hospital subsequently sustaining frostbite to both his feet. This case illustrates the management of frostbite and highlights some key principles in the management of this problem.


Prevalence of non-alcoholic fatty liver and liver fibrosis in patients with moderate-severe psoriasis: A cross-sectional cohort study.
Several studies have reported that non-alcoholic fatty liver disease (NAFLD) is more frequent in patients with psoriasis, but few have reviewed the presence of liver fibrosis in those patients. Cross-sectional cohort, single-centre study, continuously selecting all patients with moderate-severe psoriasis seen at the Psoriasis Unit of a Tertiary Hospital. The grade of liver steatosis was assessed using liver ultrasound, and the quantity of liver fibrosis was graded using a transitional vibration-controlled elastography (Fibroscan®). A total of 71 patients (66.2% male) were included, with an average age of 46.6 years old. The maximum historical PASI average was 14.4 while the baseline PASI average at the time of the study was 2. A third (36%) of patients met the criteria for metabolic syndrome 52% of patients had steatosis; being male, having metabolic syndrome comorbidities, elevated AST/ALT enzymes, dyslipidemia and high initial PASI were significantly related. 14% of patients had moderate liver fibrosis (≥7.6 KPa). In 30% of them, no ultrasound liver steatosis was observed. Elastography may be a useful tool along with ultrasound to evaluate liver disease in patients with psoriasis.


Combination of Dual Wavelength Picosecond and Nanosecond Pulse Width Neodymium-Doped Yttrium-Aluminum-Garnet Lasers for Tattoo Removal.
Tattoo removal by laser has been mostly performed using Q-switched laser, which has nanosecond pulse width. In recent years, the efficacy of treatment with picosecond pulse width laser has also been reported. Using a picosecond-domain, neodymium-doped yttrium-aluminum-garnet laser with a potassium-titanyl-phosphate frequency-doubling crystal, we performed a retrospective clinical study with combination treatment using pulse widths of 750 ps and 2 ns. The number of treatments was compared with the Kirby-Desai score. Tissue changes immediately after laser irradiation at 2 ns and 750 ps were compared using an electron microscope. The combination treatment using pulse widths of 2 ns and 750 ps was safe and more effective than the Q-switched neodymium-doped yttrium-aluminum-garnet laser treatment. Tattoo removal was possible with significantly fewer treatment numbers than the Kirby-Desai score, without adverse events. The results from the scanning electron microscope revealed that ink particles irradiated by 750 ps were more dispersed than those by 2 ns. The combination treatment with pulse widths of 2 ns and 750 ps and 1064 nm and 532 nm wavelengths using the neodymium-doped yttrium-aluminum-garnet laser was safe and effective and can be a useful option for tattoo removal. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.


Treatment of invasive grade 3 transitional cell bladder cancer. A retrospective study of 10 years' experience with external irradiation, and preoperative irradiation and cystectomy.
Three hundred and seventy-four patients with invasive grade 3 bladder cancer treated with either external irradiation or preoperative irradiation and cystectomy were re-evaluated. Cancer-free survival was markedly better for patients who underwent preoperative irradiation and operation than irradiation only, even if a complete clinical response had occurred initially.


Fat-storing cells in the liver of rats kept on a low-magnesium diet.
While studying the effect of low-magnesium diet on the rat liver considerable proliferation and enlargement of cells, identified as the Ito cells, has been observed. These events were accompanied by the accumulation of lipid substances in the cells. It is the authors' opinion that the lipid accumulation in the Ito cells is due to the deficiency in the lipid metabolising and transporting enzymes. Disturbances in the production of enzymatic proteins may result from the considerable and longlasting magnesium deficiency. The contribution of the fat-storing cells to the collagen biosynthesis is also discussed.


Role of Intraoperative Cytology in Head and Neck Lesions: A Prospective Study.
To study the technique of intra-operative imprint cytology for intraoprative diagnosis and management in cases of Head and Neck malignant lesions and to compare its result with postoperative histopathology. Prospective study conducted over 2 yrs period at the Department of ENT of a tertiary care centre in central India. A total of 60 patients who were operated for Head and Neck malignant lesions were studies with regards to intraoperative diagnosis, marginal status and lymphnodal status and compared with postoperative histopathology. Mean age-group was 47.70 (± 13.7) years. There was male preponderance. Bucco-aveolar complex lesions constituted the majority followed by Tongue and thyroid lesions. Intraoperative cytology technique showed a sensitivity of 92.98%, 80.60% and 92.30% as regards the intraoperative diagnosis, marginal clearance and nodal metastases respectively; while the specificity was 100%, 90.09% and 83.33% respectively. At the end of the study we conclude that intra-operative cytology is a good technique for intra-operative evaluation in Head and Neck lesions, where facilities for frozen section are not available. It can be used as a simple, non-expensive and rapid alternative to frozen section. A larger and longer study can validate its routine use in surgical setups where high-end pathology setup is not available.


The heterogeneity of the microcirculation in critical illness.
Microcirculation, a complex and specialized facet of organ architecture, has characteristics that vary according to the function of the tissue it supplies. Bedside technology that can directly observe microcirculation in patients, such as orthogonal polarization spectral imaging and sidestream dark field imaging, has opened the way to investigating this network and its components, especially in critical illness and surgery. These investigations have underscored the central role of microcirculation in perioperative disease states. They have also highlighted variations in the nature of microcirculation, both among organ systems and within specific organs. Supported by experimental studies, current investigations are better defining the nature of microcirculatory alterations in critical illness and how these alterations respond to therapy. This review focuses on studies conducted to date on the microcirculatory beds of critically ill patients. The functional anatomy of microcirculation networks and the role of these networks in the pathogenesis of critical illness are discussed. The morphology of microvascular beds that have been visualized during surgery and intensive care at the bedside are also described, including those of the brain, sublingual region, skin, intestine, and eyes.


South African Herbal Extracts as Potential Chemopreventive Agents: Screening for Anticancer Splicing Activity.
RT-PCR is an invaluable tool for the detection and characterization of mRNA. Cancer cell lines are treated with crude plant extracts and RNA is extracted and purified with DNase prior to RT-PCR. RT-PCR first-strand cDNA synthesis is done using random primers and can be refrigerated at 4 °C. PCR from the stored cDNA is performed using transcript-specific primers and electrophoresed on a molecular grade agarose gel to separate the splice variants.


Genetic differences and phenotypic plasticity as causes of variation in oviposition preference in Battus philenor.
Bradshaw (1965) proposed that phenotypic plasticity would be more common than adaptive genetic variability in species for which environmental fluctuations occur over periods roughly equal to that species' generation time. In an effort to examine this notion, sources of seasonal variation in two components of oviposition behavior in an east Texas population of pipevine swallowtail butterflies (Battus philenor) were investigated under natural and seminatural conditions. Variability in a visually-based prealighting component involving orientation to leaf shape was primarily due to phenotypic plasticity in the form of adult learning; no seasonally-based genotypic differences in leaf-shape discrimination behavior were observed. By contrast, a chemotactile post-alighting component involving elicitation of oviposition after landing on the host plant was not phenotypically plastic, i.e., not susceptible to learning. In addition, only slight and nonsignificant seasonally-based differences in post-alighting responses to different host species were observed.


The role of the cognitive activity context in the conservatism of unconscious visual sets.
Studies in healthy adults were performed to compare measures of the rigidity of a verbal set in three series of experiments: in series 1, pseudowords were presented at the set-forming stage of the experiment, while common words were presented in the test stage; series 2 used the pseudoword/word conditions of series 1 with the additional task of identifying the position of a target stimulus in a matrix, requiring discrimination from other symbols in terms of two characteristics; in series 3, the pseudoword/word test was followed by an initial task consisting of identifying the matrix position of a target stimulus in conditions in which the need to discriminate was minimized. The results supported the hypothesis that the rigidity of a visual set depends on the cognitive activity context. This property is significantly dependent on the loading applied to working memory and the cognitive tasks solved by the subject, particularly the ratio of involvement of the ventral and dorsal visual systems in the cortical processing of sequentially acting verbal and non-verbal visual stimuli. The cognitive set paradigm serves as a model for experimental studies of the roles of the ventral and dorsal visual systems in organizing recognition functions.


Current Evidence of Adult Stem Cells to Enhance Anterior Cruciate Ligament Treatment: A Systematic Review of Animal Trials.
To systematically review the available preclinical evidence of adult stem cells as a biological augmentation in the treatment of animal anterior cruciate ligament (ACL) injury. Systematic review. PubMed (MEDLINE) and Embase were searched for the eligible studies. The inclusion criteria were controlled animal trials of adult stem cells used in ACL treatment (repair or reconstruction). Studies of natural ACL healing without intervention, in vitro studies, ex vivo studies, and studies without controls were excluded. Evidence level, methodologic quality, and risk of bias of each included study were identified using previously established tools. Thirteen animal studies were included. Six of 7 studies using bone marrow-derived mesenchymal stem (stromal) cells (BMSCs) reported a positive enhancement in histology, biomechanics, and biochemistry within 12 weeks postoperatively. Four studies using ACL-derived vascular stem cells showed a promoting effect in histology, biomechanics, and imaging within 8 weeks postoperatively. Two studies focusing on animal tendon-derived stem cells (TDSCs) and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) reported promotable effects for the early healing in a small animal ACL model. BMSCs, ACL-derived vascular stem cells, TDSCs, and hUCB-MSCs were shown to enhance the healing of ACL injury during the early phase in small animal models. Results of clinical trials using adult stem cells in ACL treatment are conflicting, and a systematic review of the current best preclinical evidence is crucial to guide further application.


Expression of Ia antigens on the surface of human oligodendrocytes and astrocytes in culture.
Oligodendrocytes and astrocytes were isolated from normal adult human brains 3-15 h postmortem using a Percoll density gradient centrifugation and were cultured for 10-135 days. The presence of HLA-DR(Ia) antigens on the surface of these human oligodendrocytes and astrocytes was studied using double immunofluorescence procedures. Only half of separate culture series (6/12 donors) contained HLA-DR-positive oligodendrocytes, while all of the culture series (12/12 donors) revealed HLA-DR-positive astrocytes. Among the HLA-DR-positive cultures, 4-16% of galactocerebroside-positive oligodendrocytes and 9-24% of GFAP-positive astrocytes were found to immunoreact with HLA-DR antibody. The presence of Ia antigens on the surface of certain populations of oligodendrocytes and astrocytes may be important in the induction of an immune response to these cells.


DM-PhyClus: a Bayesian phylogenetic algorithm for infectious disease transmission cluster inference.
Conventional phylogenetic clustering approaches rely on arbitrary cutpoints applied a posteriori to phylogenetic estimates. Although in practice, Bayesian and bootstrap-based clustering tend to lead to similar estimates, they often produce conflicting measures of confidence in clusters. The current study proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as DM-PhyClus (Dirichlet-Multinomial Phylogenetic Clustering), that identifies sets of sequences resulting from quick transmission chains, thus yielding easily-interpretable clusters, without using any ad hoc distance or confidence requirement. Simulations reveal that DM-PhyClus can outperform conventional clustering methods, as well as the Gap procedure, a pure distance-based algorithm, in terms of mean cluster recovery. We apply DM-PhyClus to a sample of real HIV-1 sequences, producing a set of clusters whose inference is in line with the conclusions of a previous thorough analysis. DM-PhyClus, by eliminating the need for cutpoints and producing sensible inference for cluster configurations, can facilitate transmission cluster detection. Future efforts to reduce incidence of infectious diseases, like HIV-1, will need reliable estimates of transmission clusters. It follows that algorithms like DM-PhyClus could serve to better inform public health strategies.


Animal models for assessing the impact of natural products on the aetiology and metabolic pathophysiology of Type 2 diabetes.
Type 2 diabetes mellitus is a complex and heterogeneous disorder which in its most common manifestation arises from insulin resistance and later insulin insufficiency. Type 2 diabetes is characterised by impaired insulin sensitivity and diagnosed as hyperglycaemia. Because of its cardiovascular consequences, Type 2 diabetes represents one of the world's leading causes of mortality and morbidity. Drug discovery and development are required to produce better ways to prevent, treat and manage diabetes and its complications. Diabetes is a human, not an animal disease, so animals do not get Type 2 diabetes. However there are animal models which are variously suitable for the investigation of new agents for the treatment of Type 2 diabetes. In this Review we have examined the various models that are available for the study of natural products with a focus on models (genetic, nutritional and spontaneous) for the metabolic abnormities of diabetes. These models are also relevant to the investigation of Western medicines for the treatment of diabetes. A suitable experimental model plays an important role in drug discovery for translational studies leading to increased understanding of the molecular basis and management of diabetes.


Adenovirus arming human IL-24 inhibits neuroblastoma cell proliferation in vitro and xenograft tumor growth in vivo.
Data have increasingly shown that interlukin-24 (IL-24) has growth suppression activity and can induce apoptosis in a broad spectrum of tumor cells. However, the therapeutic effect of IL-24 on human neuroblastoma has rarely been explored. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to reveal the effect of adenovirus-mediated IL-24 (Ad-IL24) gene therapy for neuroblastoma. We showed that Ad-IL24 effectively inhibited the proliferation of SH-SY5Y cells in vitro by conspicuously inducing apoptosis. To further explore the molecular mechanism by which Ad-IL24 induced apoptosis in SH-SY5Y tumor cells, we found that Ad-IL24 increased the expression of Bax and promoted the activation of caspase-3, while decreasing Bcl-2 levels. We also demonstrated that Ad-IL24 significantly inhibited tumor growth in vivo in a xenograft neuroblastoma tumor in athymic nude mice. In summary, Ad-IL24 overexpression exerted potent antitumor activity via inducing apoptosis in neuroblastoma cells. Therefore, IL-24 has the potential to serve as an agent for gene therapy in the treatment of neuroblastoma.


[Effect of carminomycin on the enzyme systems of the metabolism of active forms of oxygen and on free-radical lipid oxidation in August rats with Walker carcinosarcoma 256].
The influence of carminomycin (CM) on enzymic systems of metabolism of oxygen active forms, free radical lipid peroxidation and microviscosity of membrane lipids as well as toxic and antitumour action of CM were studied in normal and tumour-bearing rats. Detected responses of the system of superoxide anion- and H2O2 metabolism reflected the role of active oxygen forms in CM toxicity. The investigation results of the lipid peroxidation fluorescent products level and microsomal lipid phase microviscosity did not suppose stimulation of lipid peroxidation as key mechanism for CM toxic effects. Problems on the prevention and treatment of anthracyclines side effects are discussed.


Evaluation of ground water denitrification at a biosolids disposal site.
A study was conducted at a sanitary sewage sludge (biosolids) disposal site in Springfield, Illinois, U.S.A. to determine if biological denitrification played a significant factor in attenuation of ground water nitrate values. The site selected for this study is a 23 ha (57 acre) dedicated biosolids disposal facility located adjacent to a 75.7 million liter per day (20 million gallons per day) municipal treatment plant that uses anaerobic solids stabilization for treatment of generated biosolids material. Biosolids have been disposed of by fixed-point spray applicators at the site since 1976, which has caused ground water nitrate levels to increase significantly above background levels. A method was developed using a conservative chemical tracer to simulate the biosolids application process and monitor the ground water directly beneath the simulated disposal site. Results demonstrated a net decline of nitrates that could not be attributed to dilution alone. While the monitoring methodology developed for this study did not directly estimate the denitrification rate, a rate for overall nitrate reduction was calculated that could be considered to take into account all transport and reduction mechanisms such as denitrification, advection, dispersion and dilution.


[Ultrasonic technique for removing bone cement in total hip revision arthroplasty].
Review of the literature and authors experience in ultrasonic technique application for cement removal at revision hip arthroplasty is presented. Ultrasonic tool proved very useful in those cases.


High-Dimensional Flow Cytometry Analysis of Regulatory Receptors on Human T Cells, NK Cells, and NKT Cells.
The field of flow cytometry has witnessed rapid technological advancements in the last few decades. While the founding principles of fluorescent detection on cells (or particles) within a uniform fluid stream remains largely unchanged, the availability more sensitive cytometers with the ability to multiplex more and more florescent signals has resulted in very complex high-order assays. This results in the co-use of fluorophores with increased levels of emission overlap and/or spillover spreading than in years past and thus requires careful and well thought out planning for flow cytometry assay development. As an example, we present the development of a large 18-color (20 parameter) flow cytometry assay designed to take an in depth analysis of effector lymphocyte phenotypes, with careful attention to assay controls and panel design.


Environmental non-occupational risk factors associated with bladder cancer.
Bladder carcinoma (BC), due its high morbidity and relapsing course, generates significant economic and health care costs. Accordingly, review the environmental nonoccupational risk factors (RF), more or less evidence-based, in the etiology and pathogenesis of BC, because the involvement of urologists is essential for prevention. Review of the peer-reviewed literature (1987-2012) on nonoccupational environmental RF associated with BC retrieved from Medline, Embase and Science Citation Index. The search profiles have been "Risk factors/Epidemiology/Tobacco-smoking/Diet-nutrition-water-liquids/Radiation/Infectious/Farmacological drugs" and "Bladder cancer". Smoking was associated with 50% of BC in both sexes. Smokers have a 2-5 times higher risk than nonsmokers, directly proportional to the amount and duration of addiction. Drinking water contaminated with arsenic and chromium chlorination byproducts increases the risk of BC. High consumption of red meat and saturated fat may increase the risk, while high intake of fruits and vegetables decreases it. Patients treated with cyclophosphamide, ifosfamide and ionizing radiation have an increased risk of BC. Frequent and prolonged use of hair dyes and Schistosoma haematobium infestation increases the risk of BC. The reduction or the cessation of smoking decrease BC. The contaminant-free water consumption with the increase of vegetal foods favour BC prevention. Cancer survivors treated with cyclophosphamide, ifosfamide and radiation therapy should be monitored for early diagnosis of BC.


Dietary glycine protects from chemotherapy-induced hepatotoxicity.
Hepatotoxic side effects of neoadjuvant chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality. Glycine protects liver from injury in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy. Sprague-Dawley rats (200-220 g) were fed a synthetic diet containing 5% glycine for 5 days. Subsequently, chemotherapy (FOLFIRI: irinotecan, folinic acid and fluorouracil, or FOLFOX: oxaliplatin, folinic acid and fluorouracil) was administered at standard doses. Transaminases, histology, immunohistochemistry and in vivo microscopy were used to index liver injury, to monitor intrahepatic microperfusion and activation of Kupffer cells. Glycine significantly decreased transaminases after chemotherapy to 25-50% of control values (p < 0.05). Microvesicular steatosis was significantly reduced from 18.5 ± 3.4 and 57.1 ± 8.6% in controls to 9.5 ± 1.8 and 37.7 ± 4.4% after FOLFIRI and FOLFOX, respectively. Furthermore, phagocytosis of latex beads was reduced by about 50%, while leukocyte adherence in central and midzonal subacinar zones decreased to 60-80% after glycine (p < 0.05). Glycine significantly reduced expression of inducible nitric oxide synthase after chemotherapy, while hepatic microcirculation was increased (p < 0.05). This study shows for the first time that glycine reduces chemotherapy-induced liver injury. The underlying mechanisms most likely include Kupffer cells and an improved intrahepatic microperfusion.


Morphometric characterization and temporal temperature measurements during hepatic microwave ablation in swine.
Heat-induced destruction of cancer cells via microwave ablation (MWA) is emerging as a viable treatment of primary and metastatic liver cancer. Prediction of the impacted zone where cell death occurs, especially in the presence of vasculature, is challenging but may be achieved via biophysical modeling. To advance and characterize thermal MWA for focal cancer treatment, an in vivo method and experimental dataset were created for assessment of biophysical models designed to dynamically predict ablation zone parameters, given the delivery device, power, location, and proximity to vessels. MWA zone size, shape, and temperature were characterized and monitored in the absence of perfusion in ex vivo liver and a tissue-mimicking thermochromic phantom (TMTCP) at two power settings. Temperature was monitored over time using implanted thermocouples with their locations defined by CT. TMTCPs were used to identify the location of the ablation zone relative to the probe. In 6 swine, contrast-enhanced CTs were additionally acquired to visualize vasculature and absence of perfusion along with corresponding post-mortem gross pathology. Bench studies demonstrated average ablation zone sizes of 4.13±1.56cm2 and 8.51±3.92cm2, solidity of 0.96±0.06 and 0.99±0.01, ablations centered 3.75cm and 3.5cm proximal to the probe tip, and temperatures of 50 ºC at 14.5±13.4s and 2.5±2.1s for 40W and 90W ablations, respectively. In vivo imaging showed average volumes of 9.8±4.8cm3 and 33.2±28.4cm3 and 3D solidity of 0.87±0.02 and 0.75±0.15, and gross pathology showed a hemorrhagic halo area of 3.1±1.2cm2 and 9.1±3.0cm2 for 40W and 90W ablations, respectfully. Temperatures reached 50ºC at 19.5±9.2s and 13.0±8.3s for 40W and 90W ablations, respectively. MWA results are challenging to predict and are more variable than manufacturer-provided and bench predictions due to vascular stasis, heat-induced tissue changes, and probe operating conditions. Accurate prediction of MWA zones and temperature in vivo requires comprehensive thermal validation sets.


Permanent neurological sequelae due to lithium toxicity.
Lithium intoxication is well known to produce acute and chronic symptoms but development of permanent neurological deficit is a rarity. Six cases of manic depressive psychosis who developed neurological sequelae following treatment with lithium carbonate are described. There were multiple lesions in the central nervous system. However, the main brunt was borne by cerebellum. The serum lithium levels of five patients were within therapeutic range. The value of identifying the precipitating factors, early diagnosis and prompt intervention in the prevention of persistent neurological dysfunction is emphasized.


Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly.
Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.


Body size, time and dimensions of oxygen diffusion.
The body masses of extant mammals span over seven orders of magnitude. Within that size range there is extraordinary diversity of function, phylogenetic diversity that understandably presents fertile ground for uncovering biological insights. Remarkably transcending that diversity, are patterns that reveal body size-dependent constraints of "form and function", patterns that become visible only through comparison. Thus, "Comparative Physiology" provides an additional tool for discovery of additional biological insights that may be otherwise hidden. Among these are the linear (isometric) scaling of volumes and the disproportionate (allometric) scaling of biological times and rates. When the diffusion of oxygen through the lungs and tissues is re-examined through this lens it is apparent that body size alone has profound impacts. The smallest mammals have no apparent "structural reserve;" oxygen diffusion in both the lungs and tissues is apparently functioning at full capacity. Because small body size is the ancestral state, it may be an evolutionary consequence of increased body size that large mammals seem to have "excess capacity" for oxygen diffusion in both the lungs and tissues. There is scant evolutionary evidence that physiological variables pivot around "normal" values of humans.


Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinson's Disease.
Levodopa-carbidopa intestinal gel (LCIG; Duodopa®) is used for continuous infusion in advanced Parkinson's disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses.


Role of tropoelastin fragmentation in elastogenesis in rat smooth muscle cells.
Neonatal rat aortic smooth muscle cell cultures produce two major soluble elastin molecules termed protropoelastin (77 kDa) and tropoelastin (71 kDa). Cell layer extracts are protroproelastin-enriched, while protropoelastin, tropoelastin, and significant amounts of discrete elastin fragments (Mr of 66,000, 61,000, 56,000, and 45,000) are present in preparations from the medium of these cultures. To determine the role of the various elastin molecules in the metabolism of elastin in neonatal rat aortic smooth muscle cell cultures, the amino termini of these proteins were sequenced. All soluble elastin components present in the medium were purified as a single peak by high performance liquid chromatography; further separation of the components was achieved by polyacrylamide gel electrophoresis and electroblotting. The bands were excised and sequenced. The amino-terminal sequences of protropoelastin, tropoelastin, and the 66-kDa, 61-kDa, and 56-kDa fragments were identical: Gly-Gly-Val-Pro-Gly-Ala-Val-Pro-Gly-Gly. This sequence is identical with published amino-terminal sequences of tropoelastins from several other species. As expected, when the cell cultures were pulsed with [3H]valine, all the soluble elastin molecules were radioactive, while only protropoelastin appeared radioactive after [35S] cysteine pulsing. Since cysteine is present only in the carboxyl-terminal end of the molecule, all the data indicate that the cleavage of the elastin fragments identified in the culture are occurring at the carboxyl end of protropoelastin. These results are consistent with the original hypothesis that a precursor-product relationship exists between the 77-kDa and 71-kDa soluble elastin molecules. Based on known tropoelastin sequences and the molecular weights of the discrete fragments, additional fragmentation of protropoelastin and/or tropoelastin most likely occurs at the lysine/alanine-enriched domains presumably involved in cross-link formation.


Partial cloning of CB1 cDNA and CB1 mRNA changes in stress responses in the Solea solea.
Endogenous cannabinoids, through the CB1 receptor, are involved in the control of several functions including stress responses. The aim of this study was to investigate the presence of cannabinoid receptor CB1 in the sole ovary by partial cloning of brain CB1 cDNA; in a stress paradigm of disturbance by handling, which consisted in catching, netting and hand-sorting, changes of CB1 mRNA were related with those of proopiomelanocortin (POMC) mRNA; the trend and timing of stress responses and adaptation were monitored by measuring plasma cortisol levels. We characterized two forms of CB1-like receptor, termed CB1A and CB1B. The two sole CB1 (both 799bp) share 76% identity in their cDNAs, and the deduced amino acid sequences are 80% identical. The handling stress induced a sustained increase in plasma cortisol levels 1h after the handling began and decreased to low levels 12h after initiation of handling, showing the same trend of ovarian POMC mRNA expression. In addition, while CB1A mRNA did not show any significant changes during handling stress, significantly lower levels of CB1B mRNA were found in stressed fish 1h after the beginning of handling, with CB1 expression increased 24h after stress induction, both in the ovary and brain. It can be concluded that endocannabinoid system is involved in the modulation of adaptive responses to environmental conditions.


Snaring of a coronary artery causing distal atheroma embolization.
We report a case of total occlusion of the left anterior descending coronary artery with atheromatous debris after "off-pump" grafting. Atheroma break-off and distal embolization probably occurred from proximal snare occlusion of the target coronary artery, and this was recognized by intraoperative angiography. Alternatives to suture snaring should be considered whenever an atherosclerotic artery is to be grafted without cardiopulmonary bypass.


Intensive rotational grazing assists control of gastrointestinal nematodosis of sheep in a cool temperate environment with summer-dominant rainfall.
While rotational grazing methods have an accepted role in the management of gastrointestinal nematodosis (GIN) of small ruminants in humid tropical regions, their efficacy and application in cool temperate regions is more controversial. This study evaluated GIN over 2 years in three classes of fine wool Merino sheep (lambs, hoggets and ewes) under three different sheep management systems in a cool tableland environment near Armidale NSW Australia (950m altitude, 30 degrees 31'S, 151 degrees 39'E). The management systems were High input (HI) with high fertiliser inputs, a target of 100% sown pasture, high stocking rate (13.4 dry sheep equivalents/ha) and relatively long grazing periods; Typical (TYP) New England management system with moderate fertiliser inputs and stocking rate (9.3DSE/ha) and relatively long grazing periods; and Intensive rotational grazing (IRG) with moderate fertiliser inputs and stocking rate (8.8DSE/ha) but very short (mean 5 days) grazing periods and long (mean 103 days) rest periods. Twenty sheep of each class in each management treatment were sampled monthly for faecal worm egg counts (WEC, followed by larval differentiation), and body weights with a blood sample taken for haematology every second month. The proportion of sheep with WEC above zero did not differ between management systems but the magnitude of WEC did, with sheep under IRG displaying lower mean WEC than those on the other treatments (IRG: 326, HI: 594, TYP: 536, eggs/g P<0.0001). This was despite a significantly longer mean interval between anthelmintic treatments (IRG: 144 days, HI: 77 days, TYP: 78 days, P<0.0001). The IRG management system also influenced the composition of the infections with sheep on this treatment having a significantly lower proportion of Haemonchus contortus in their faecal cultures (IRG: 59.7%, HI: 79.4%, TYP: 80.9%, P<0.05) and a significantly higher proportion of Trichostrongylus spp. Sheep on the IRG treatment also had a significantly higher haematocrit (HCT) than those on the other management systems. Despite the lower WEC and higher HCT, sheep under IRG also had significantly lower bodyweights and fleece weights overall, although this was only evident in sheep raised to adulthood prior to the experiment, not those raised during the 2-year experimental period. The results demonstrate that IRG systems with short grazing periods and long rest periods between grazing events can assist with control of GIN in cool temperate climates where H. contortus is the dominant parasite.


Kinematics and paraspinal muscle activation patterns during walking differ between patients with lumbar spinal stenosis and controls.
The narrowing of the spinal canal due to degenerative processes may lead to symptomatic lumbar spinal stenosis (sLSS) and impairments in the patients' gait. Changes in lower extremity joint kinematics and trunk flexion angles have been reported, yet less is known about muscle activation patterns of paraspinal and gluteal muscles in patients with sLSS compared to healthy participants. Do muscle activation patterns together with sagittal joint kinematics differ between patients with sLSS and healthy controls and do these differences-quantified using gait scores-correlate with clinical scores? In 20 patients with sLSS scheduled for surgery and 19 healthy participants, gait was assessed using seven inertial sensors and muscle activation of gluteus medius, erector spinae and multifidus using wireless surface electromyography (EMG). Differences in joint kinematics and EMG patterns were assessed using statistical parametric mapping with non-parametric independent sample t tests (P < 0.05). Gait scores that describe the overall deviation in joint angles (mGPS) and muscle activation patterns (EMG-Profile Score) were calculated as root mean square distances between patients and healthy participants and their associations with clinical scores (pain, Oswestry Disability Score (ODI)) were analyzed using Spearman's correlation coefficients rho (P < 0.05). Patients had larger mGPS (+1.9°) and EMG-Profile Scores (+50%) and walked on average slower (-0.26 m/s) than controls. EMG patterns revealed higher activation of multifidus, erector spinae and gluteus medius during midstance in patients compared to controls. Clinical scores (pain, ODI) did not correlate with mGPS or EMG-Profile Scores within patients. Observed differences in gait and muscle activation patterns and in the summary scores of gait and EMG deviations between patients with sLSS and healthy controls may represent additional functional outcomes reflecting the functional status of patients that can be measured using wearable sensors and hence is suitable for application in clinical practice.


Bacteriophages isolated from Lake Michigan demonstrate broad host-range across several bacterial phyla.
The study of bacteriophages continues to generate key information about microbial interactions in the environment. Many phenotypic characteristics of bacteriophages cannot be examined by sequencing alone, further highlighting the necessity for isolation and examination of phages from environmental samples. While much of our current knowledge base has been generated by the study of marine phages, freshwater viruses are understudied in comparison. Our group has previously conducted metagenomics-based studies samples collected from Lake Michigan - the data presented in this study relate to four phages that were extracted from the same samples. Four phages were extracted from Lake Michigan on the same bacterial host, exhibiting similar morphological characteristics as shown under transmission electron microscopy. Growth characteristics of the phages were unique to each isolate. Each phage demonstrated a host-range spanning several phyla of bacteria - to date, such a broad host-range is yet to be reported. Genomic data reveals genomes of a similar size, and close similarities between the Lake Michigan phages and the Pseudomonas phage PB1, however, the majority of annotated genes present were ORFans and little insight was offered into mechanisms for host-range. The phages isolated from Lake Michigan are capable of infecting several bacterial phyla, and demonstrate varied phenotypic characteristics despite similarities in host preference, and at the genomic level. We propose that such a broad host-range is likely related to the oligotrophic nature of Lake Michigan, and the competitive benefit that this characteristic may lend to phages in nature.


Clinical significance of anaplasia in childhood rhabdomyosarcoma.
The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age⩾10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8±10.6% and 53.4±5.8%, respectively (p=0.014) and the 3-year overall survival rates were 35.3±11.6% and 61±6%, respectively (p=0.019). The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome.


Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat.
1. The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2. Administration of either NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3. In capsaicin-pretreated rats, however, L-NMMA (12.5-100 mg kg-1 i.v.) dose-dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer D-NMMA (100 mg kg-1 i.v.) did not induce any detectable mucosal damage. 4. This mucosal injury induced by L-NMMA was inhibited by concurrent administration of L-arginine (300 mg kg-1 i.v.). 5. In indomethacin (5 mg kg-1 i.v.)-pretreated rats, L-NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin-pretreated rats, L-NMMA induced widespread, severe haemorrhagic necrotic damage. 6. These findings suggest a role for endogenous NO formed from L-arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.


Uptake of inert microparticles in normal and immune deficient mice.
Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles.


Advances in congenital heart surgery.
We provide an overview of the past year's literature on congenital heart surgery. This review focuses on selected disease entities, operative techniques, perioperative management strategies, and quality of care. Congenital heart surgery is an evolving field.


Virus-Induced Gene Silencing in Maize with a Foxtail mosaic virus Vector.
Virus-induced gene silencing (VIGS) is a powerful technology for rapidly and transiently knocking down the expression of plant genes to study their functions. A VIGS vector for maize derived from Foxtail mosaic virus (FoMV), a positive-sense single-stranded RNA virus, was recently developed. A cloning site created near the 3' end of the FoMV genome enables insertion of 200-400 nucleotide fragments of maize genes targeted for silencing. The recombinant FoMV clones are inoculated into leaves of maize seedlings by biolistic particle delivery, and silencing is typically observed within 2 weeks after inoculation. This chapter provides a protocol for constructing FoMV VIGS clones and inoculating them into maize seedlings.


Sensorineural hearing loss due to cochlear otospongiosis: etiology.
This presentation discusses the most valuable way to correlate specific morphologic changes in cochlear otospongiosis with sensorineural hearing loss. Both biochemical and vascular factors may be responsible for the association of far advanced otospongiosis and histopathologic changes. An enzymatic concept of the disease is proposed on the basis of experimental findings and cytoclinical correlations, and the spread of proteolytic enzymes from the bursting lysosomes in histiocytes of the otospongiotic microfoci of the lateral wall. In addition, according to Ruedi's vascular concept, abnormal vascular connections called "shunts", provoked by active foci breakiny oxygen. Such extensive otospongiotic bone transformation breaking the endosteum of the cochlear is much less frequent than the progressive cochlear component encountered by otologic surgeons in far advanced otospongiosis. It is for this reason that the authors believe that their enzymatic concept of otospongiosis may explain the most important part of the sensorineural impairment in cochlear otospongiosis.


Tyrosine kinase expression profile in clear cell renal cell carcinoma.
To profile different tyrosine kinase (TK) expression patterns in clear cell renal carcinoma (ccRCC). We analysed mRNA expression levels of 89 receptor and non-receptor TK in corresponding cancer and normal renal tissue from 5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and corresponding normal renal tissues was performed, applying quantitative real-time PCR. To confirm mRNA expression levels on protein level, we studied ERBB4 and HCK using immunohistochemistry. A total of 12 TK were significantly upregulated in ccRCC (ABL2, FLT1, BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK, PTPRC, FYN and CSK), coherently 7 TK demonstrated a down-regulation (ERBB4, PDGFRA, NRTK3, SYK, ERBB2, FGFR3 and PTK7). These findings were validated by the utilization of RT-PCR for ABL2, FLT1 BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK and vice versa for ERBB4 and PDGFRA. Immunohistochemistry revealed ERBB4 expression to be significantly lower in ccRCC in comparison to papillary RCC, chromophobe RCC, renal oncocytoma and normal renal tissue (P < 0.001). HCK protein expression was reduced in ccRCC in contrast to papillary RCC (P < 0.001) or oncocytoma (P = 0.023), but similar to chromphobe RCC (P = 0.470), sarcomatoid RCC (P = 0.754) and normal renal tissue (P = 0.083). Neither ERBB4 nor HCK were correlated (P > 0.05) with clinical-pathological parameters. TK constitute valuable targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict significantly lower expression levels in renal cancer tissues.


Quantitative Analysis of Thymus-Independent Donor-Derived T Cell Expansion in Transplant Patients.
Although thymus-independent donor-derived T cell expansion may determine the occurrence of graft-versus-host disease (GVHD) and relapse after transplantation, the characteristics and dynamics of the expansion process remain unclear. To address this issue, we monitored T cell receptor β repertoire at day 0, day 28, and day 61 after transplantation in 30 patients with hematologic malignancies by next-generation sequencing. The clonality index showed an increasing clonality over time (P = .001). The top 200 clonotypes accounted for more than half of the total clonotypes (median frequency, 63.55%) at day 61, and there was a remarkable overlapping between the top 200 clonotypes of each repertoire and its former repertoire (>50%). A normalized index, called the T Cell Response Index (TCRI), was designed on the basis of rank-shift analysis to quantify antigen-driven expansion. The TCRI during the first month was not related to relapse or GVHD (P> .05), whereas the TCRI during the second month was related to relapse (P = .006). Recipients with a TCRI below 1.0 during the second month had a higher cumulative relapse rate (31.25% versus 0%, P = .0323) and had a lower 1-year survival rate (56.25% versus 78.57%, P = .281). The clonotypes with strong competitiveness in the second month in the nonrelapse group preferentially used TRBV2, TRBV12-3, TRBJ1-1 and TRBJ1-5 segments (P< .01). In conclusion, homeostatic expansion predominates in the first month due to nonspecific T cell proliferation, whereas antigen-driven expansion predominates in the second month and results in a graft-versus-tumor (GvT) effect. Moreover, TCRI could serve as a quantitative indicator of GvT against relapse within the first year. The difference in V and J segment usage reveals that T cells responsible for potent GvT effect are similar among patients.


Detection of rare prostate cancer cells in human urine offers prospect of non-invasive diagnosis.
Two molecular cytology approaches, (i) time-gated immunoluminescence assay (TGiA) and (ii) Raman-active immunolabeling assay (RiA), have been developed to detect prostate cancer (PCa) cells in urine from five prostate cancer patients. For TGiA, PCa cells stained by a biocompatible europium chelate antibody-conjugated probe were quantitated by automated time-gated microscopy (OSAM). For RiA, PCa cells labeled by antibody-conjugated Raman probe were detected by Raman spectrometer. TGiA and RiA were first optimized by the detection of PCa cultured cells (DU145) spiked into control urine, with TGiA-OSAM showing single-cell PCa detection sensitivity, while RiA had a limit of detection of 4-10 cells/mL. Blinded analysis of each patient urine sample, using MIL-38 antibody specific for PCa cells, was performed using both assays in parallel with control urine. Both assays detected very low abundance PCa cells in patient urine (3-20 PCa cells per mL by TGiA, 4-13 cells/mL by RiA). The normalized mean of the detected PCa cells per 1 ml of urine was plotted against the clinical data including prostate specific antigen (PSA) level and Clinical Risk Assessment for each patient. Both cell detection assays showed correlation with PSA in the high risk patients but aligned with the Clinical Assessment rather than with PSA levels of the low/intermediate risk patients. Despite the limited available urine samples of PCa patients, the data presented in this proof-of-principle work is promising for the development of highly sensitive diagnostic urine tests for PCa.


Effects of epinephrine on thermoregulatory behavior in lean and obese Zucker rats in the cold.
This series of experiments examined whether epinephrine (EPI) produces the same thermoregulatory effects in the cold that have been reported for norepinephrine and isoproterenol. Lean and obese Zucker rats were trained to press a lever to activate infrared heat lamps in a cold (-8 degrees C) environment. Operant thermoregulatory behavior increased dose-dependently following EPI (0-100 micrograms/kg), but posttest colonic temperature (Tc) fell. Thermal balance calculations showed a substantial increase in net heat loss, more so in obese than lean animals. EPI is therefore thermolytic--i.e., disrupts thermal balance. A low dose (100 micrograms/kg) of the alpha-antagonist phentolamine produced a marked improvement in operant behavior, Tc, and thermal balance, whereas a comparable dose of the beta-antagonist propranolol had no beneficial effect. Increasing the dose of phentolamine worsened the responses with respect to the 100-micrograms/kg dose. The selective alpha 1-antagonist prazosin ameliorated the decrease in Tc induced by EPI but had little effect on operant behavior or thermal balance; the selective alpha 2-antagonist yohimbine had no effect on any parameter compared to EPI alone. These results suggest that the paradoxical effects of EPI in the cold are mediated by alpha-adrenoceptors, but definitive identification of the subclass of receptor involved cannot be determined.


Project 6 Summit: SAGES telementoring initiative.
Advances in telecommunications technology have facilitated telementoring initiatives that virtually link a mentor and mentee in the operating room and have shown significant promise in conferring high rates of safe procedure adoption. Recognizing that telementoring has the potential to be one solution to the global demand for what is sure to be a constant need for surgical retraining and safe incorporation of new technologies, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) convened the Project 6 Summit. Content experts in minimally invasive surgery, surgical mentoring and telementoring, surgical education, business development, healthcare innovation, and regulation were invited to attend a two-day summit to outline the current state of surgical telementoring and chart the challenges and opportunities going forward. Five opportunity buckets consisting of: Legal and Regulatory, Business Development and Proving Value, Effective Communication and Education Requirements, Technology Requirements and Logistics were the subject of focused working groups and subsequent review and consensus by summit attendees. The current state-of-the-art and guiding principles are presented herein. Telementoring activities are poised for exponential growth but will require a coordinated effort by stakeholders working through and around a healthcare system not yet suited for this paradigm shift.


Food intolerance in patients with manifest autoimmunity. Observational study.
In the professional medical and scientific world, there is not many interest in the correlation of food intolerance and autoimmune diseases. However there is a lot of evidence that e.g. gluten or gliadine can induce autoimmmune diseases: example the interest in coeliac disease and autoimmunity. There is however a lot of informationavailable about leaky gut and autoimmunity. We performed an observational study in our data base;, where we selected 100 patients with manifest autoimmune disease with clear symptoms and autoimmune antibodies in the form of positive anf more tehn 160 titer. These patients were compared with 25 control patients without any autoimmunity. We could clearly find a difference in food intolerance profiles when we compared AI patients with people without any AI. Overall there is a much greater reaction to several food epitopes, which can be observed on the level of specific antibodies tot he food epitopes. These igG levels for specific food antibodies are significantly higher in the patient group then in the control group. We can also see that some food epitopes provocate a very pronounced reaction, while other show no increased level of igG. Among the most reactive food epitopes are caseine, cow milk, wheat, gliadine, white of egg and rice. A variable reaction can bes een on nuts e.g.; walnuts and almonds. Almost no antibody reaction is noticed on vegetables, fish and meat products, who seem tob e immunologially very neutral. We conclude that food intolerance test is very important tool in patients with AI disease, and should be performed in each patient to tailor an individual diet program, which if properly followed, could relieve symptoms and probably stop or slow the the progression of the autoimmune disease. Also interesting for global research in AI disease is the fact that food is probably an important trigger for autoimmunity in vulnerable patients. More research on great scale and multicenter around this topic is mandatory and urgent.


Adolescents in crisis: A geographic exploration of help-seeking behavior using data from Crisis Text Line.
Nearly 3 out of 4 all lifelong mental disorders occur by the age of twenty-four. Remote crisis support holds great potential in filling a critical gap in complementing and expanding access to mental health services for acute episodes of mental distress in adolescents and young adults; yet little is understood about the individual factors that influence help-seeking behavior in this group. Recent evidence suggests technology-based mental health services have high acceptability among youth and may be used to treat anxiety and depression. The objective of this study was to examine county-level help-seeking behavior among adolescents and young adults using Crisis Text Line (CTL). CTL is a free, text-based crisis counseling service that has been available nationally since 2013. Spatial error regression was used to (1) identify the individual-level factors that correlate with help-seeking behavior for depression, anxiety, and suicidal thoughts and (2) to explore the geographic trends in text-based help-seeking behavior between adolescents and young adults across the rural-urban continuum. Increased rates of text-based help-seeking occurred in counties with higher mean household incomes, higher divorce rates, and lower residential stability. Rurality was the strongest predictor for low rates of help-seeking, and this finding is particularly concerning in light of elevated rates of suicide among rural counties. Rural communities, particularly those with low support-seeking behavior and comparatively high suicide rates, should be the target of future research and outreach.


A new turn-on fluorimetric method for the rapid speciation of Cr(III)/Cr(VI) species in tea samples with rhodamine-based fluorescent reagent.
A new fluorimetric method with rhodamine-based fluorescent agent was developed for the rapid speciation of Cr(III)/Cr(VI) in tea, soil and water samples. The system, which utilizes a fluorescent reagent, was used for the first time after synthesis/characterization of 3',6'-bis(diethylamino)-2-{[(1E)-(2,4-dimethoxyphenyl)methylene] amino}spiro[isoindole-1,9'-xanthen]-3(2H)-one (BDAS). The reagent responds instantaneously at room temperature in a 1:1 stoichiometric manner to the amount of Cr(III). The selectivity of this system for Cr(III) over other metal ions is remarkably high, and its sensitivity is below 0.01mgL-1 in aqueous solutions which enables a simplification without any pretreatment of the real sample. The method has a wide linear range of 0.1-10mgL-1 and a detection limit of 0.15μgL-1 for Cr(III) while the relative standard deviation was 0.1% for 0.1mgL-1 Cr(III) concentration. The results of detection and recovery experiments for Cr(III) in tea, soil and water were satisfactory, indicating that the method has better feasibility and application potential in the routine determination and speciation of Cr(III)/Cr(VI). The results of analysis of the certified reference material (INCT-TL-1 tea sample and CWW-TM-D waste water) are in good agreement with the certified value.


Schedule-dependent synergism of edatrexate and cisplatin in combination in the A549 lung-cancer cell line as assessed by median-effect analysis.
The methotrexate analog edatrexate has been shown to have greater antitumor activity and an improved therapeutic index as compared with its parent compound in preclinical systems. These studies suggest that edatrexate may have a broad role in the treatment of solid tumors. Information regarding edatrexate in combination with other chemotherapeutic agents is limited. We evaluated the interaction of edatrexate with cisplatin in vitro as assessed by median-effect analysis in the A549 human lung-cancer cell line. The effects of dose, exposure time, and schedule dependence were assessed. Cytotoxicity was evaluated using the tetrazolium-based colorimetric (MTT) assay. The inhibitory concentration producing 50% absorbance (IC50 for edatrexate with 1 h exposure was 1.4 microM. For all combination experiments, the edatrexate dose was fixed at 0.2 microM (IC10) whereas cisplatin (CDDP) concentrations were varied for 1-, 3-, and 24-h exposures either before or after edatrexate treatment. Drug interactions were assessed using the combination-index method as defined by median-effect analysis. A synergistic interaction was documented in experiments when edatrexate was applied prior to CDDP (combination index, < 1). The combination studies in which edatrexate was used prior to CDDP resulted in significant reduction of all three CDDP IC50 values: 1-h IC50, from 30.0 to 3.9 microM; 3-h IC50, from 21.3 to 1.4 microM; and 24-h IC50, from 1.7 to 0.03 microM. In contrast, synergism was not observed in experiments in which edatrexate treatment occurred after cisplatin exposure. Median-effect analysis is a useful method of determining drug interactions. In the present study, the combination of edatrexate and CDDP demonstrated schedule-dependent synergism, with the synergism being observed only in the setting of edatrexate treatment before CDDP exposure. Due to the potential broad spectrum of activity of edatrexate plus CDDP, further studies are warranted to determine the mechanism responsible for the synergism and to investigate this combination in a variety of tumor models.


Molecular basis for "null" lipoprotein(a) phenotypes and the influence of apolipoprotein(a) size on plasma lipoprotein(a) level in the baboon.
High plasma levels of lipoprotein(a) (Lp(a)) and its unique apolipoprotein, apo(a), are an independent risk factor for cardiovascular disease. Plasma Lp(a) levels vary over a 1000-fold range and are determined by the apo(a) locus, which has at least 34 alleles expressing apo(a) isoforms with molecular weights from < 300,000 to > 800,000. In addition, "null" apo(a) alleles produce no detectable plasma apo(a). We used primary cultures of baboon hepatocytes to investigate the molecular basis for null apo(a) phenotypes. Immunoprecipitation of apo(a) after radiolabeling of hepatocytes revealed that some null alleles gave rise to intracellular protein products that were not secreted. Pulse-chase analysis and endoglycosidase digests demonstrated that these proteins were retained in the endoplasmic reticulum. We also examined the molecular basis for the documented inverse correlation between apo(a) size and plasma Lp(a) concentration. Steady-state labeling and pulse-chase analysis of hepatocytes from animals expressing two isoforms of apo(a) revealed that the endoplasmic reticulum residence time of secreted apo(a) isoforms was determined by their size. This accounted for the inverse relationship between isoform size and level of secretion. We conclude that the efficiency of post-translational processing of apo(a) is a major determinant of plasma Lp(a) concentration.


[Periradicular infiltration therapy : Clinical indications, technique and results].
Minimally invasive procedures have played an emerging role in pain management during recent years. Evaluation of the different types of periradicular infiltration as fundamental procedures in the progressive stepwise concept of pain management. Comparison of the different therapeutic substances. In the mid-term and long-term periradicular infiltration is effective in 60-80 % of patients regarding analgesic and functional aspects. Compliance with the guidelines should help to minimize potentially fatal complications. Periradicular infiltration is of significant importance concerning the treatment of spinal nerve root irritation. Periradicular infiltration is regarded as a safe procedure, especially when supported by computed tomography (CT) scans.


Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats.
The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male.


Tim4 regulates NALP3 inflammasome expression and activity during monocyte/macrophage dysfunction in septic shock patients.
Sepsis is the leading cause of death in burn patients. Monocytes/macrophages rapidly exhibit impaired production of proinflammatory cytokines and an elevated generation of anti-inflammatory cytokines in septic patients with immunosuppression. However, the expression patterns of Tim4 and Nod-like receptor protein 3 (NALP3) inflammasome and their roles during immunosuppression in septic shock patients are not well understood. Tim4 and NALP3 inflammasome expression in monocytes were downregulated in immunosuppressive patients with sepsis compared with healthy volunteers. Meanwhile, NALP3 inflammasome expression was upregulated by Tim4 overexpression in murine bone marrow-derived macrophages (BMDMs) and J774A.1 macrophages. Tim4 overexpression improved the ability of BMDMs and J774A.1 macrophages to produce proinflammatory cytokines and increased the expression of cleaved-caspase-1 (p10) after LPS/ATP stimulation. In addition, overexpression of Tim4 enhanced phagocytosis of apoptotic polymorphonuclear neutrophils (PMNs) by BMDMs and J774A.1 macrophages, while depletion of NALP3 in Tim4 overexpressing BMDMs and J774A.1 macrophages decreased phagocytosis of apoptotic PMNs. In summary, the expression of Tim4 and NALP3 inflammasome in monocytes/macrophages was downregulated in septic shock patients, and diminished expression of Tim4 and NALP3 inflammasome in monocytes/macrophages might play a critical role in sepsis-elicited immunosuppression.


Pulmonary function studies of conjoined thoracopagus twins.
Lung functions were measured on 13-day-old conjoined thoracopagus twins. Mean values for tidal volume and minute ventilation were 14.8 ml and 1102 ml/min for twin A and 12.8 ml and 963 ml/min for twin B. Functional residual capacities (FRC) were 35 ml/kg and 39 ml/kg for twins A and B, respectively. Pulmonary compliance and flow resistance for twin A were 2.8 ml/cm H2O and 75 cm H2O/liter.sec-1 with 45% of the total work used to overcome elastic resistance. Although values for resistance and work of breathing are within the normal range for studies reported elsewhere, these results tend to be elevated and probably reflect an abnormal state.


Cloning and paratope analysis of an antibody fragment, a rational approach for the design of a PAI-1 inhibitor.
This study reports the cloning, characterization and paratope analysis of the plasminogen activator inhibitor-1 (PAI-1) neutralizing single-chain variable fragment 56A7C10 (scFv-56A7C10). ScFv-56A7C10-wt exhibits a similar affinity (KA = 1.01 +/- 0.3 x 109 m-1) and PAI-1 inhibitory capacity (90 +/- 6% PAI-1 inhibition at a 16-fold molar excess and IC50 = 44 +/- 14 ng mL-1) as MA-56A7C10 (KA = 1.43 +/- 0.4 x 109 m-1, 90 +/- 2% PAI-1 inhibition at a 16-fold molar excess and IC50 = 122 +/- 26 ng mL-1). Subsequently, alanine scanning of the six complementarity determining regions (CDRs) was performed and the scFv-56A7C10-mutants (n = 26) were analyzed for their PAI-1 binding and PAI-1 inhibitory properties. Mutation of the residues Y32 and V33 in the CDR1 of the heavy chain (HCDR1) and the residues R98, H99, W100 or F100a (HCDR3) resulted in reduced PAI-1 inhibitory capacities (IC50 >/= 418 ng mL-1), confirmed by reduced affinities (14-, 17-, 7-, 9- and 16-fold reduced, respectively, vs. scFv-56A7C10-wt). In the light chain, mutation of the residues W50 (LCDR2), H91, Y92, D93, or W96 (LCDR3) resulted in reduced PAI-1 inhibitory properties (IC50 >/= 160 ng mL-1) and decreased affinities (i.e. 4-, 9-, 3-, 3- and 2-fold reduced affinity, respectively, vs. scFv-56A7C10-wt). Furthermore, an overlapping peptide scan confirmed the importance of the HCDR3 region. These data, combined with a three-dimensional model of scFv-56A7C10, reveal the molecular and structural properties of the paratope and contribute to the rational design of PAI-1 neutralizing compounds.


Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition.
R2 is a non-LTR retrotransposable element that inserts at a specific site in the 28S rRNA genes of most insects. We have expressed the open reading frame of the R2 element from Bombyx mori, R2Bm, in E. coli and shown that it encodes both sequence-specific endonuclease and reverse transcriptase activities. The R2 protein makes a specific nick in one of the DNA strands at the insertion site and uses the 3' hydroxyl group exposed by this nick to prime reverse transcription of its RNA transcript. After reverse transcription, cleavage of the second DNA strand occurs. A similar mechanism of insertion may be used by other non-LTR retrotransposable elements as well as short interspersed nucleotide elements.


The majority of calf muscle cell messenger RNAs contain poly(A).
Previous studies from our laboratory have investigated messenger RNA metabolism in calf muscle cells in tissue culture. The analysis of mRNA was based on its poly(A) content. We have now examined directly the proportion of mRNA which contains poly(A) in these cells. After separation of poly(A)+ -and poly(A) - -RNA on oligo(dT) -cellulos, the two fractions were translated in a reconstituted, heterologous cell-free protein-synthesizing system and the products were compared with those from the translation of total RNA. The great majority of mRNA form either prefusion or postfusion cultures was poly(A)- containing; quantitative determinations show that about 70-90% of the actin mRNA is poly(A)-containing. In order to determine if a large fraction of the calf muscle mRNA can be translated by a heterologous cell-free system, [3H]-POLY(A)+ -RNA was added to reticulocyte lysates and the formation of initiation complexes was followed. These experiments suggest that the bulk of calf muscle cell mRNA would be utilized in such a system and justify the use of cell-free systems to examine the poly(A) content of total mRNA. Thus, differential polyadenylation does not seem to be an important aspect of mRNA metabolism in cultured muscle cells. The previous study of mRNA in these cells, based on poly(A) content, is apparently a valid measure of overall mRNA metabolism.


The duality of the inflammatory response to traumatic brain injury.
One and a half to two million people sustain a traumatic brain injury (TBI) in the US each year, of which approx 70,000-90,000 will suffer from long-term disability with dramatic impacts on their own and their families' lives and enormous socio-economic costs. Brain damage following traumatic injury is a result of direct (immediate mechanical disruption of brain tissue, or primary injury) and indirect (secondary or delayed) mechanisms. These secondary mechanisms involve the initiation of an acute inflammatory response, including breakdown of the blood-brain barrier (BBB), edema formation and swelling, infiltration of peripheral blood cells and activation of resident immunocompetent cells, as well as the intrathecal release of numerous immune mediators such as interleukins and chemotactic factors. An overview over the inflammatory response to trauma as observed in clinical and in experimental TBI is presented in this review. The possibly harmful/beneficial sequelae of post-traumatic inflammation in the central nervous system (CNS) are discussed using three model mediators of inflammation in the brain, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). While the former two may act as important mediators for the initiation and the support of post-traumatic inflammation, thus causing additional cell death and neurologic dysfunction, they may also pave the way for reparative processes. TGF-beta, on the other hand, is a potent anti-inflammatory agent, which may also have some deleterious long-term effects in the injured brain. The implications of this duality of the post-traumatic inflammatory response for the treatment of brain-injured patients using anti-inflammatory strategies are discussed.


Drop-out and efficacy of group versus individual cognitive behavioural therapy: What works best for Obsessive-Compulsive Disorder? A systematic review and meta-analysis of direct comparisons.
Cognitive behavioural therapy (CBT) is the first-line psychological treatment for Obsessive-Compulsive Disorder (OCD). However, a relevant proportion of individuals with OCD remain untreated or inadequately treated. Group cognitive behavioural therapy (GCBT) may be an alternative treatment modality. Little knowledge is available about the efficacy between GCBT versus individual CBT, particularly on long-term secondary outcomes including anxiety and depression. In addition, drop-out rates have not been investigated by previous meta-analyses. The current systematic review and meta-analysis summarized evidence comparing drop-out rates between GCBT and individual CBT and efficacy at post-treatment and follow-up on OCD symptoms, depression and anxiety. A systematic review and meta-analysis according to PRISMA guidelines was conducted. Online databases were searched. Studies were included if using randomized designs comparing GCBT versus individual CBT. Six studies were included (n = 327). No difference was found between GCBT and individual CBT on drop-out rates with a medium non-significant effect. No difference resulted at post-treatment on OCD symptoms, depression, and anxiety. Analyses on a smaller number of studies indicated no difference at follow-up. Findings provided preliminary evidence that GCBT can be as effective as individual CBT. Further trials are required with higher quality and long-term assessments of quality of life.


Protective activity of a murine monoclonal antibody against European bat lyssavirus 1 (EBL1) infection in mice.
A mouse model was designed to test in vivo the efficacy of rabies immune globulins and specific neutralizing monoclonal antibodies to prevent European bat lyssavirus 1 infection. Human or equine rabies immune globulins previously found to contain variable amounts of neutralizing bat lyssavirus crossreactive antibodies were passively transferred to mice receiving intramuscularly a lethal dose of bat lyssavirus type 1. Immune globulins did not protect mice well against bat lyssavirus 1 whereas they reduced the mortality caused by rabies virus. In contrast, mice inoculated with bat lyssavirus 1 or rabies virus survived when passively immunized with bat lyssavirus 1 specific monoclonal antibody (mAb 8-2). This monoclonal antibody, an IgG2 alpha, recognized an epitope located in the antigenic site IIa of rabies glycoprotein. A mutation replacing the lysine 198 by glutamate in a rabies variant abrogated sensitivity to this neutralizing antibody. Because of its broad neutralizing spectrum against wild virus isolates, including European bat lyssaviruses, this monoclonal antibody should be a good candidate for rabies immune globulin replacement. It could improve efficacy of rabies vaccination, used either alone or in conjunction with human rabies immune globulins or monoclonal antibody cocktail to supplement their lack of crossreactivity to European bat lyssavirus 1.


Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma.
Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future.


Coupling of ssRNA cleavage with DNase activity in type III-A CRISPR-Csm revealed by cryo-EM and biochemistry.
The type III CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated genes) systems are bacterially encoded adaptive immune systems for defense against invading nucleic acids. They accomplish this task through the coordinated cleavage of invading substrates of single-stranded RNA and DNA (ssDNA and ssRNA) by the Csm (type III-A) or Cmr (type III-B) effector complexes. The ssRNA is complementarily bound to the CRISPR RNA (crRNA). However, the structural basis for the DNase and RNase activation of the Csm nucleoprotein complex is largely unknown. Here we report cryo-EM structures of the Csm-crRNA complex, with or without target ssRNA, at near-atomic resolution. Our cryo-EM maps allow us to build atomic models of the key macromolecular components, including Cas10, Csm2, Csm3, Csm4, crRNA and the invading ssRNA. Our structure resolves unambiguously the stoichiometry and tertiary structures of the Csm protein complex and the interactions between protein components and the crRNA/ssRNA. Interestingly, the new atomic structures of the Csm proteins presented here are similar to those of previously known Csm proteins in other species despite their low sequence similarity. Our combined structural and biochemical data suggest that ssRNA cleavage is preferentially carried out near its 5'-end, that the extent of interactions among the ssRNA, crRNA and the protein components regulates the DNase activity of the Csm complex, and that the 3' flanking sequence of ssRNA activates the Cas10 DNase activity allosterically.


Specificity of human anti-carbohydrate IgG antibodies as probed with polyacrylamide-based glycoconjugates.
The TF, Tn, and SiaTn glycotopes are frequently expressed in cancer-associated mucins. Antibodies to these glycotopes were found in human serum. A set of polyacrylamide (PAA)--based glycoconjugates was applied to the direct and competitive enzyme-linked immunosorbent assays (ELISA) to characterize the specificity of serum IgG antibodies. The anti-TF, -Tn and -SiaTn IgG were affinity purified from serum of cancer patients and characterized using PAA-conjugates and free saccharides. The anti-TF and -Tn antibodies were shown to be specific. The anti-TF IgG bound both Galbeta1-3GalNAcalpha- and Galbeta1-3GalNAcbeta-PAA, the latter was three-four times more effective inhibitor of antibody binding. The anti-Tn IgG reacted only with GalNAcalpha-PAA. The anti-SiaTn IgG cross-reacted with Tn-PAA but SiaTn-PAA was five-six times more effective inhibitor in a competitive assay. The IC50 values for PAA-conjugates with the corresponding antibodies typically ranged from 2 to 5 x 10(-8) M. The antibodies display a low specificity to mucin-type glycoconjugates in comparison with PAA-conjugates as was shown for mucins isolated from human malignant tumor tissues, ovine submaxillary mucin (OSM) and asialo-OSM. The unusual IgG-antibody specificity to GalNAcbeta and GalNAcbeta1-3GalNAcbeta ligands was found in human serum.


Improvement of visual acuity after transcorneal electrical stimulation in case of Best vitelliform macular dystrophy.
To report an improvement of the visual acuity after transcorneal electrical stimulation (TES) in a case of Best vitelliform macular dystrophy (BVMD). A 26-year-old woman diagnosed with BVMD presented with reduced vision. Her best corrected visual acuity (BCVA) was reduced to 20/200 in the right eye, and TES was performed once a month for two sessions. The current of the biphasic pulses (anodic first; duration, 10 msec; frequency, 20 Hz) was delivered using a DTL-electrode, and the duration of the TES was 30 min. The BCVA in the right eye slowly improved after the TES, and 6 months later the BCVA was 20/25. The results of Humphrey visual field tests (VF) and multifocal ERGs (mfERGs) were only slightly changed. Two years later, the BCVA decreased, and it was improved again after another session of TES with the same parameters of the electrical pulses. The improvement of the visual acuity in our case of BVMD indicates that TES should be tried in other cases of retinal dystrophy. Further clinical and laboratory studies on TES are needed.


U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2.
Sequence analysis of the U2 regions of the B95-8 and AG876 Epstein-Barr virus (EBV) isolates reveals divergence within a long open reading frame previously identified as encoding 1.5 kilobases of the 3' end of a viral RNA expressed in latently infected, growth-transformed, B-lymphocyte cell lines. Differences among EBV isolates within the U2 open reading frame are shown to correlate with differences in an EBV nuclear antigen, EBNA2. B95-8, W91, Raji, Cherry, and Lamont EBV isolates have similar U2 domains and encode similar-size EBNA2 proteins, while AG876, Jijoye, and P3HR-1 have variant or absent U2 domains and variant or absent EBNA2 proteins. The AG876 U2 open reading frame and EBNA2 protein are both shorter than those of B95-8. These data indicate that the U2 open reading frame encodes EBNA2.


Inhibition of human antigen-specific T cell proliferation by anti-T blast sera.
Two antisera, one raised against activated human T lymphoblasts and one raised against the human T cell line HPB-ALL, have the ability to inhibit antigen-induced T cell proliferation. Antiproliferative activity is absorbed by T blasts and HPB-ALL cells, but not by B lymphoblastoid cell lines, alpha-ethylisothiouronium bromide-treated sheep red blood cell (AET-SRBC) receptor-negative lymphoid cells, or the T cell lines MOLT-4 and HSB. The effects of these antisera do not require the presence of complement and are not attributable to toxicity during culture. The F(ab')2 fragment of anti-T blast antiserum is also active.


Processing of four different cooking methods of Oudemansiella radicata: Effects on in vitro bioaccessibility of nutrients and antioxidant activity.
The purpose of this study is to evaluate the bioaccessibility of nutrients and antioxidant activity of O. radicata after subjecting to four types of domestic cooking and followed by in vitro digestion. The result demonstrated that the group with the lowest amino acid release and the degree of protein hydrolysis (5.6%) was frying, but both reducing sugar content and antioxidant activity were the highest. The composition of fatty acids was different than undigested samples, especially the relative content of linolenic acid was significantly decreased (e.g., 34.49 to 8.23%, boiled). The difference of the minerals bioaccessibility was slightly affected by the cooking method, but mainly related to their natural properties, such as the highest phosphorus (62.73%) and the lowest iron (21.53%) in the steaming. The above data provides a starting point for the design of processes at an industrial and gastronomic level.


Joubert syndrome: Clinical and radiological characteristics of nine patients.
Joubert Syndrome (JS) is a rare genetic developmental disorder, first identified in 1969. In patients with JS, certain regions of the brain (mainly cerebellar vermis and brainstem) are underdeveloped or malformed. This can lead to impaired attention, visual, spatial, motor, language and social functional skills. JS is characterized by a host of features, many of which do not occur in every patient. To spotlight and increase awareness of clinical profile and neuroimaging findings of children with Joubert syndrome. This is a retrospective case series study of patients with JS who attended the Pediatric Neurology Clinic in Aladan and Alfarawanya Hospitals in Kuwait, from September 2007 to September 2012. Clinical and radiological data were obtained from the patient medical records. Cerebellar vermis hypoplasia/aplasia and apnea were present in all patients, polydactly in 3 of 16, renal problems with cysts in 5 patients and 11 of 16 had abnormal electroretinograms (ERGs). Blood investigations of organic acids, amino acids and very-long-chain fatty acid, were normal in the all the nine patients. JS is a rare genetic brain malformation with association of retinal dystrophy and renal abnormalities. The retinal dystrophy may be progressive. The prognosis of patients depends mainly on the degree of brain malformation.


Conditioning the pecking motions of pigeons.
The spatio-temporal courses of head and neck motions of pigeons while pecking at small grains are described. Single and serial pecks are distinguished but the inter- and intraindividual variability of the peck kinetics is stressed. Pigeons were then trained with instrumental conditioning procedures to speed-up their pecking. A partial reinforcement schedule where pigeons had to peck repeatedly before receiving reward led to a mild shortening of inter-peck intervals at lower reinforcement rates but surprisingly, a lengthening at higher rates. A schedule where short inter-peck intervals were differentially rewarded yielded a pronounced abbreviation of the inter-peck intervals, but this was achieved by a reduction of the movement path rather than an increase in motion velocity. A schedule whereby increased approach velocities were differentially rewarded yielded marked movement accelerations. When pigeons were rewarded for diminished approach speeds they also showed significant movement decelerations. Finally, it is shown that pigeons could learn to reliably abort their peck approach movement when a visual stimulus signalling a penalty was occasionally presented during the approach movement. The proportion of successful peck interruptions decreased as these interruption signals occurred later during the approach phase. It is concluded that the pecking of pigeons is neither an innately fixed nor a visually ballistic movement. It is instead a multiply controlled and flexibly adaptable response pattern.


FoxP3+, and not CD25+, T cells increase post-transplant in islet allotransplant recipients following anti-CD25+ rATG immunotherapy.
Anti-CD25 antibodies are used as an induction therapy in islet allotransplantation for type 1 diabetes. Although previous reports suggested that anti-CD25 treatment may lead to depletion of CD4+CD25+ regulatory T cells (Tregs) and questioned its use in tolerance-promoting protocols for transplantation, the effect of anti-CD25 antibodies on the frequency and function of Tregs remains unclear. We examined the effect of anti-CD25 antibody, daclizumab, in vivo on Tregs in islet allograft recipients enrolled in a single-center study and monitored post-transplant. Our data shows that the reduction in CD25+ Treg cells observed post-transplant is due to masking of CD25 receptor by daclizumab and not due to depletion. In addition, using Treg marker, FoxP3, we show that anti-CD25+ ATG treatment leads to an increase in FoxP3+ Tregs post-transplant. These data suggest that anti-CD25-based therapy has beneficial effects on Tregs and combined with ATG may be a promising therapy for autoimmunity and transplantation.


[Pension Due to Full Reduction in Earning Capacity: Do Psychiatric Reports Meet the Quality Criteria for Socio-Medical Assessment?]
The quality of socio-medical expert opinions, which are prepared for the German Pension Insurance (GPI) in the context of applications for reduced earning capacity pension due to mental disorder, has hardly been investigated so far. The aim of the present study was to investigate to what extent expert medical reports on post-traumatic stress disorder (PTSD) comply with the guideline of the GPI on socio-medical reports for mental and behavioral disorders. To examine the quality of expert opinions, 52 socio-medical expert opinions in which a diagnosis of post-traumatic stress disorder (PTSD) was assigned and a performance capacity of less than three hours was determined were analyzed. The quality of the expert opinions was assessed both quantitatively by calculating quality points and qualitatively by analyzing the content. Percent agreement and Cohen's kappa were calculated for two raters to examine rater agreement based on a subsample (n=11). The analyzed appraisals scored an average of 36.1 (SD=7.4) out of a possible 92 quality points (range 22/56). In most of the expert opinions, the descriptions of participation limitations, epicrisis, and sociomedical conclusion were unsatisfactory. The inadequate presentation of the functional and participation limitations in the expert opinions may not do justice to the actual facts of the case, so that the evidence of a health disorder with the corresponding participation limitations cannot be provided beyond doubt. Accordingly, measures to improve the quality of expert opinions such as training and regular quality reviews are necessary.


A glycine-cleavage complex as part of the folate one-carbon metabolism of Plasmodium falciparum.
The glycine-cleavage complex (GCV) and serine hydroxymethyltransferase represent the two systems of one-carbon transfer that are employed in the biosynthesis of active folate cofactors in eukaryotes. Although the understanding of this area of metabolism in Plasmodium falciparum is still at an early stage, we discuss evidence that genes and transcription products of the GCV are present and expressed in this parasite. The potential role of the GCV and its relevance to the life cycle and pathogenesis of the malaria erythrocytic stages are also considered. According to its expression profile, the GCV seems to be particularly active in gametocytes. The GCV enzyme dihydrolipoamide dehydrogenase has two isoforms encoded by two different genes. It has been demonstrated recently that both genes are functional, with one of them identified as being part of a pyruvate dehydrogenase complex that is present exclusively in the apicoplast of Plasmodium species. The other isoform probably forms part of the Plasmodium GCV. The GCV is the first enzyme complex involved in folate metabolism in this parasite that can be assumed, with a good degree of certainty, to be located in the mitochondria.


Two new glucoside derivatives of truxinic and cinnamic acids from Lavandula angustifolia mill.
A phytochemical investigations on the n-butanol fraction of Lavandula angustifolia Mill. residues resulted in the isolation of ten compounds, including two new ones, 4,4'dimethoxy-2,2'di-O-β-d-glucopyranosyl-truxinate (1) and 2-(β-d-glucosyloxy)-trans-cinnamic acid butyl ester (2), along with eight known compounds. The structures of compounds were confirmed by NMR and HR-ESI-MS techniques and comparison with published data. The NMR data for 3 were attributed for the first time. Compound 2 was proofed to be a natural compound in plant rather than a butyl ester artifact formed by esterification reaction with butanol by comparative HPLC-DAD analysis with the ethanol extract which was obtained prior to the application of butanol. All isolated compounds were evaluated for their antioxidant and anti-hypoglycaemic activities. Among them, compounds 4 and 5 showed strong anti-oxidant activities against DPPH with IC50 values of 12.99 and 31.74 μM, respectively. Compound 5 exhibited moderate inhibitory activity against PTP1B with an IC50 value of 31.28 μM.