Lacosamide-Induced Recurrent Ventricular Tachycardia in the Acute Care Setting.
Lacosamide is a new-generation antiepileptic drug (AED) most commonly used adjunctively in the setting of partial-onset seizures refractory to traditional therapy. We describe the first case report, to our knowledge, of a patient who developed recurrent, sustained ventricular tachycardia with multiple administrations of lacosamide in an acute setting. A 70-year-old woman with a history significant for valvular heart disease was admitted to the inpatient cardiology service for worsening heart failure. On hospital day 7, she received a bioprosthetic aortic valve. Prior to surgery and immediately after, the patient's electrocardiogram (ECG) was normal. After developing multiple generalized tonic-clonic seizures refractory to levetiracetam, fosphenytoin, and valproic acid, the decision was made to initiate lacosamide. Two hours following the second lacosamide dose, the patient developed a wide complex QRS that transitioned into sustained ventricular tachycardia requiring electrical cardioversion. Sustained ventricular tachycardia occurred again, just hours after the third dose of lacosamide was given. Following cessation of lacosamide, the patient's QRS interval normalized and has since had no documented episodes of ventricular tachycardia. Clinicians should be aware of the potential for life-threatening rhythmic disturbances in patients initiated on lacosamide and the need for vigilant ECG, electrolyte, and drug-drug monitoring.


Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: Results from a multicenter, prospective study.
In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard-of-care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2-5 ng/mL) until after month 6 post-enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m2 . Two patients experienced treated biopsy-proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2-18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.


Time-dependent contrast effects in a multiple schedule of food reinforcement.
Four rats were rewarded for running in a wheel under two alternating conditions of food reinforcement. These periods of frequent and infrequent reinforcement, each accompanied by a particular stimulus, were presented a number of times in each daily session. Following shifts from high to low frequency of reinforcement, responding decreased suddenly and markedly, and then recovered within the next few minutes. The magnitude of this temporary depression was an increasing function of the duration of the immediately preceding component of high-frequency reinforcement. A transient elevation in performance, which did not vary with the duration of the prior component, was noted in two subjects following shifts from low to high frequency of reinforcement. The elevation and depression effects did not appear simultaneously during the 48 experimental sessions. A possible relation between the difficulty of the discrimination and the extent of contrast effects is discussed.


Nanoparticle platforms for dermal antiaging technologies: Insights in cellular and molecular mechanisms.
Aging is a continuous process defined by a progressive functional decline in physiological parameters. Skin, being one of the most vulnerable organs, shows early signs of aging which are predominantly affected by intrinsic factors like hormone, gender, mood, enzymes, and genetic predisposition, and extrinsic factors like exposure to radiation, air pollution, and heat. Visible morphological and anatomical changes associated with skin aging occur due to underlying physiological aberrations governed by numerous complex interactions at cellular and subcellular levels. Nanoparticles are perceived as a powerful tool in the cosmeceutical industry both for augmenting the efficacy of existing agents and as a novel standalone therapy. Both organic and inorganic nanoparticles have been extensively investigated in antiaging applications. The use of nanoparticles helps to enhance the activity of antiaging molecules by selectively targeting cellular and molecular pathways. On the other hand, the nanoparticle platforms also gained increasing popularity as the skin protectant against extrinsic factors such as UV radiation and pollutants. This review comprehensively discusses skin aging and its mechanism by highlighting the impact on cellular, subcellular, and epigenetic elements. Importantly, the review elaborates on the examples of organic and inorganic nanoparticle-based formulations developed for antiaging application and provides mechanistic insights on how they modulate the mechanisms of skin aging. The clinical progress of nanoparticle antiaging technologies and factors that impact clinical translation are also explored. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study.
Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the Optical Quality Analyzing System, Visiometrics (OQAS). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an ocular surface disease index (OSDI) score >23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there were no significant variations in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204, P<0.05), the average slope of OSI (0.04 versus 0.01, P<0.05) and the number of blinks (4.2 versus 2.8, P<0.05). Among the patients, 65% preferred the OF eye, 24% did not have a preference, and 11% preferred the normal saline eye. Objective quality of vision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a reduction of dry eye symptoms such as poor quality of vision. This study demonstrates that 0.5% carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear film and thus a significant improvement in the quality of vision compared to normal saline.


[Distribution of mononuclear cells in peripheral blood of females with spontaneous abortion].
The quantitative distribution of peripheral T cells, monocytes/granulocytes, natural killer cells and B cells was estimated in aborting women using the peroxidase-antiperoxidase technique with monoclonal antibodies. 30 women with spontaneous abortions were included in the study and 30 fertile and 50 healthy pregnant women as control groups. It could established that the normal pregnancy has no influence on the distribution of mononuclear cells. In cases with threatened abortions was the number of monocytes/granulocytes and of natural killer cells increased if the loss of pregnancy occurred. The differentiation of mononuclear cells may be helpful for the prognosis of abortions.


Control of Yersinia enterocolitica in raw pork and pork products by gamma-irradiation.
gamma-Radiation response of Y. enterocolitica 5692 and 152 was studied at 0 degrees C and at -40 degrees C in phosphate buffer (pH 7.00) as well as in 10% raw meat/salami homogenate. The strains investigated did not differ in their response and were found to be sensitive to gamma-radiation but exhibited a tailing phenomenon in the survival curve. The D10 in homogenate was 0.25 kGy at 0 degrees C. This response was not affected at -40 degrees C. Storage studies of packs, inoculated artificially with heavy inoculum of Y. enterocolitica (10(6) cfu/g) showed that while samples of salami and cooked ham could be decontaminated at doses of 4 and 3 kGy respectively; cells could not be eliminated from raw pork meat even at the higher dose of 6 kGy. The role of different treatments given prior to irradiation for revival of Y. enterocolitica after irradiation storage was studied. The dose of 1 kGy at -40 degrees C was efficient in eradicating low numbers (< 10(3)) of naturally occurring of Y. enterocolitica from raw pork meat without any revival during storage at refrigeration temperature.


The Norton score: an early warning of pressure sores?
This paper investigates the predictive power of the Norton score in the problem of anticipating pressure lesions, and looks at some variants on that score. The Norton score is now nearly 20 years old but is still not in frequent use by nurses, and has been the subject of little research, especially in its predictive ability. By following the progress of two matched samples over a 15-month period in a district general hospital it is established that the Norton score does perform at least as well as a number of reasonable variants of it, and that in particular the physical score and incontinence score are the crucial elements. A follow-up sample in which the variants are retested confirms the usefulness of the Norton score.


Active fixation of a thin transvenous left-ventricular lead by a side helix facilitates targeted and stable placement in cardiac resynchronization therapy.
Suboptimal placement, phrenic nerve stimulation, and dislodgements of left-ventricular (LV) leads are main challenges in cardiac resynchronization therapy. We investigated the handling, performance, safety, and stability for a novel 4Fr LV lead with a small side helix located proximal to the ring electrode for active fixation of the LV lead. The novel LV lead was successfully implanted in 103 of 106 patients. Patients with dislodged LV leads and with demanding coronary vein anatomies were included. The lead body was rotated clockwise to engage the active fixation side helix in the vein wall. The stimulating electrode was located in basal LV segment and middle LV segment in 54 and 46% of the patients, respectively. The lead was targeted to a vein concordant to the LV segment with latest mechanical activation. Concordant LV lead placement was achieved in 73% of the patients and in adjacent segment in 24%. The average pacing capture threshold (PCT) at implantation was 1.04 ± 0.6 V (n = 103) and at an average follow-up at 7 months, the PCT remained low and no dislodgements have been observed. During follow-up, four leads have been explanted without complications. Active fixation of this 4Fr LV lead by using a side helix, offers flexibility to place the lead precisely in targeted vein segments over a wide range of vein anatomies. The average LV pacing threshold was low at implantation and follow-ups. The lead seems to be extractable and no late dislodgements have been observed.


The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors.
Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.


A comparative study of spiramycin and erythromycin in acute tonsillo-pharyngitis.
In a clinical and bacteriological study of 42 patients with acute tonsillo-pharyngitis or chronic tonsillo-pharyngitis with acute exacerbation, patients were allocated at random to receive either a 3-day course of spiramycin or a 5-day course of erythromycin, both antibiotics being given in a dosage of 500 mg 3-times daily. The median time to disappearance of patient complaints such as fever, difficulty in swallowing, sore throat, cough and mucus was 3 days in each group and there was a significant reduction from pre-treatment to normal levels in total white cell count and erythrocyte sedimentation rate after treatment. Although more patients were considered to have shown a good clinical response to spiramycin, the difference was not statistically significant. From a bacteriological point of view, however, treatment with the regimen used was considered a failure in all cases in that neither antibiotic completely eradicated the pathogens identified at the start of treatment even though, with 3 exceptions, all of the micro-organisms were shown to be sensitive to the antibiotics before and after treatment. Few side-effects were reported in either group.


Chemical Markers for Short- and Long-Term Areca Nut Exposure.
Background: Areca nut (AN) chewing causes oral cancer. AN cessation programs are the most effective approach to reduce AN chewing induced cancers but require biomarkers to determine program compliance and success. Objectives: To explore chemical markers for short- and long-term AN exposure using non-invasively collected saliva, buccal cells (BCs), and scalp hair of chewers. Methods: Saliva was collected from a male chewer before and up to 2 days after AN chewing. Saliva was separated into supernatant and pellet (BCs) then analyzed by spectrophotometry and liquid chromatography (LC) with UV/VIS detection. Scalp hair was collected from four chewers and analyzed for areca alkaloids using direct analysis in real time-tandem mass spectrometry (DART-MSMS). Results: The red pigmented saliva after chewing showed no valuable signals when either the saliva supernatant or pellet (BCs) were analyzed by spectrophotometry. Saliva analysis by LC-UV/VIS showed diagnostically valuable signals at 488 nm up to 5 and 24 h post chewing in the supernatant and pellet, respectively. DART-MSMS analysis detected two of the four AN specific alkaloids (arecoline and arecaidine) in male but none in female hair. Conclusions/Importance: LC-UV/VIS analysis of the red pigments extracted from saliva and BCs after AN chewing showed distinct signals up to 24 h post chewing while DART-MSMS analysis in BCs and scalp hair showed selective signals of AN alkaloids for several weeks or months after AN exposure. Chemical hair treatment might prevent detection of areca alkaloids in hair. AN cessation trials and other programs now have essential tools for bioverification.


MM 14201, a new epoxyquinone derivative with antibacterial activity produced by a species of Streptomyces.
A new antibiotic designated MM 14201 has been detected in a culture of Streptomyces sp. NCIB 11813. Methods for the production and purification of MM 14201 are described. Biological evaluation has shown it has broad spectrum antibacterial activity being most effective against Serratia and Pseudomonas sp. Structural studies are reported which have demonstrated MM 14201 is a new epoxyquinone derivative.


Factors associated with survival exceeding 5 years after transcatheter arterial embolization for hepatocellular carcinoma.
During the period between April 1981 and March 1988, 232 consecutive patients underwent transcatheter arterial embolization (TAE) for hepatocellular carcinoma at the Department of Radiology, Wakayama Medical College. A > or = 5-year course calculated from the time of the initial TAE was able to be confirmed in 216 patients, who became the subjects of this study. Five-year survival rates were calculated by the direct method, while the clinical features existing at the time of the initial therapy and the clinical course of patients surviving > or = 5 years were studied. The 5-year survival rate was 6.0%. Comparison of the patients dying within 1 year and the patients surviving for > or = 5 years revealed differences in the severity of liver cirrhosis and the tumor type. The long-term survivors tended to have low serum alpha-fetoprotein values. The clinical picture of the patients surviving > or = 5 years after TAE was characterized by relatively mild liver cirrhosis (Child's class A or B), a serum alpha-fetoprotein value of < or = 1,500 ng/dL, relatively small nodular-type tumors with a maximum main tumor diameter of < or = 5.5 cm, a tumor-occupying rate of less than 20%, and absence of portal vein involvement by the tumor. There were patients in whom a relatively small number of TAE sessions was effective in controlling the tumor for a prolonged period, with the patients then dying of causes unrelated to the tumor, as well as patients in whom proliferation of the tumor was controlled by numerous applications of transcatheter therapy, resulting in > or = 5-year survival but with eventual death due to the tumor. Transcatheter arterial embolization makes a major contribution to achieving long-term survival of > or = 5 years in patients with hepatocellular carcinoma.


How list composition affects the emotional enhancement of memory in younger and older adults.
Young adults show an immediate emotional enhancement of memory (EEM) when emotional and non-emotional information are presented in mixed lists but not pure lists, but it is unclear whether older adults' memories also benefit from the cognitive factors producing the list-composition effect. The present study examined whether the list-composition effect extended to older adults (55+), testing the following alternatives: (1) younger and older adults could show the list-composition effect, (2) due to age-related decreases in cognitive resources, older adults may show weaker effects of list-composition, or (3) due to age-related positivity effects, older adults' list-composition effect may vary by valence. Results supported the first alternative: the list-composition effect occurred for older as well as younger adults, when testing memory for pictures (Experiment 1) or words (Experiment 2). In a third experiment, we explored whether mixing information at only encoding or retrieval (and blocking in the other phase) would suffice for the list composition effect to occur. Results revealed that mixed encoding/blocked retrieval did not elicit the EEM in either age group. Overall, the results suggest age-related stability in the cognitive processes that give rise to the immediate EEM.


[About the impact of the dendritic cell autovaccine on the results of treatment of non-small-cell lung cancer patients].
In thoracic department of the National Cancer Institute studied the effectiveness of dendritic cell autovaccine in the postoperative period in non-small-cell lung cancer patients. The results, showing good tolerance dendritic cell autovaccine. Shows the formation of the expressed antigen immune response after repeated injections dendritic cell autovaccine, as manifested after 4 revaccination. Results of survival patients non-small-cell lung cancer who received postoperative dendritic cell autovaccines demonstrate the high efficiency of the method and its applicability with a minimum of side effects. Further study of survival of patients non-small-cell lung cancer who received immunotherapy treatment, monitoring of compliance with the best mode of repeated injections.


Incidence, Risk Factors and Effective Treatment Strategies for Chylothorax After Pediatric Heart Surgeries: Retrospective Analysis of Large Database in Single Institution.
Risk factors for postoperative chylothorax in children who had cardiothoracic procedures are not always clear. Due to complex course in post-operative care, It's always challenging to find the risk factors, and their management. The aim of our study was to identify the incidence, risk factors and effective treatment approaches for chylothorax after pediatric heart surgery. Children who had the cardiac surgery and subsequently developed chylothorax were included in the study. The ratio of the experimental group to the control group was 1:2. Decannulations of extracorporeal membrane oxygenation (ECMO) were not included in the analysis of patient outcomes. For each patient, we keep track of their age, weight, gender, syndrome, RACH-1 scoring, fluid balance, bypass time, clamp time, redo operations, open or close heart surgeries, and rhythm difficulties. Care logs were kept for every single therapy that was administered. Primary outcome was chylothorax, with secondary outcomes included time in the intensive care unit (ICU), length of hospital stay (LOS), and death. 5210 surgeries were performed in six years. 96 patients developed the chylothorax with incidence of 1.8%. In chylothorax group, mean weight was 6.7 ± 4.2, while mean age was 11.7 ± 15.2. Clamp time was 74.5 ± 53.5 versus 39.9 ± 13.7. Mean bypass time was 128.34(76.25) versus 84.3 ± 25.1 with an odds ratio 1.02 (Z test 0.0001). Six (6.3%) children with chylothorax had redo cardiac surgeries in the same admission (p-value 0.01) while none in other. Five (5.2%) cases got operated by thoracotomy, three from left side. Mean Chest tube duration was 10±7.8 days versus 3.8±2.4 in control group. (p-value 0.02). chylothorax resolved (mean resolving time = 4 days) in 76 (79.2%) children with monogen formula. Two patients receive midodrine with no significant effect. Four children underwent surgical repair for chylothorax. Bypass time linearly increases incidence of chylothorax. Younger age, low weight, syndromic children, redo operations, non-open-heart surgeries, and arrhythmias also contribute to this. Gender, fluid balance, and RACHS-1 Scoring were not significant. While further research and testing are required for the use of midodrine. However, the low-fat formula of Monogen has proven to be an effective treatment.


Changes in retinol-binding protein concentrations and thyroid homeostasis with nonoccupational exposure to DDT.
The insecticide dichlorodiphenyltrichloroethane (DDT) has been used for malaria vector control in the northern and eastern parts of the Vhembe District of Limpopo Province, South Africa, since 1945. Bioaccumulation of DDT raises concern because it reportedly affects thyroid function. Our objective was to investigate the association between DDT uptake (as reflected in plasma concentrations) and thyroid homeostasis while considering related factors. We compared dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations, and liver and thyroid function between cases with evidence of a body burden of DDT in the circulation (concentration of any DDT isomer ≥ 0.02 µg/g lipid; n = 278) and controls (concentration of all DDT isomers < 0.02 µg/g lipid; n = 40) in a cross-sectional study. Further analyses were performed to assess the relevance of changes in RBP status associated with DDT uptake. RBP concentrations below the reference range were more prevalent in cases (54% vs. 10% in controls; χ² = 27.4; p < 0.001), which could not be explained by nutrient intake. We observed significantly lower thyroid hormone concentrations among cases (p ≤ 0.01). We also observed a significant linear trend for serum concentrations of free thyroxine and free triiodothyronine (p < 0.001) and a significant quadratic trend for serum thyroid-stimulating hormone (p = 0.025) and TTR (p < 0.001) across the control group and case groups with normal and relatively low RBP concentrations. Relatively low RBP concentrations were associated with significantly higher DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) isomer concentrations and with a higher DDE/DDT ratio (p ≤ 0.01), which signifies long-term exposure. Inadequate intake of vitamin A and zinc were observed in 84% and 58%, respectively, of the total study population. RBP concentrations appear to decrease in the presence of long-term DDT uptake, which may have deleterious effects on thyroid function and vitamin A nutritional status. This is of major concern in a population with poor vitamin A and zinc intake.


Down for the count: Cryptosporidium infection depletes the gut microbiome in Coquerel's sifakas.
Background: The gut microbiome (GMB) is the first line of defense against enteric pathogens, which are a leading cause of disease and mortality worldwide. One such pathogen, the protozoan Cryptosporidium, causes a variety of digestive disorders that can be devastating and even lethal. The Coquerel's sifaka (Propithecus coquereli) - an endangered, folivorous primate endemic to Madagascar - is precariously susceptible to cryptosporidiosis under captive conditions. If left untreated, infection can rapidly advance to morbidity and death. Objective: To gain a richer understanding of the pathophysiology of this pathogen while also improving captive management of endangered species, we examine the impact of cryptosporidiosis on the GMB of a flagship species known to experience a debilitating disease state upon infection. Design: Using 16S sequencing of DNA extracted from sifaka fecal samples, we compared the microbial communities of healthy sifakas to those of infected individuals, across infection and recovery periods. Results: Over the course of infection, we found that the sifaka GMB responds with decreased microbial diversity and increased community dissimilarity. Compared to the GMB of unaffected individuals, as well as during pre-infection and recovery periods, the GMB during active infection was enriched for microbial taxa associated with dysbiosis and rapid transit time. Time to recovery was inversely related to age, with young animals being slowest to recover GMB diversity and full community membership. Antimicrobial treatment during infection caused a significant depletion in GMB diversity. Conclusions: Although individual sifakas show unique trajectories of microbial loss and recolonization in response to infection, recovering sifakas exhibit remarkably consistent patterns, similar to initial community assembly of the GMB in infants. This observation, in particular, provides biological insight into the rules by which the GMB recovers from the disease state. Fecal transfaunation may prove effective in restoring a healthy GMB in animals with specialized diets.


Surgical trainees and trauma emergencies.
An accident and emergency (A&E) training has been suggested as an essential part of the basic surgical training. The A&E curriculum should be divided into three sections: a critical curriculum, a core curriculum and a comprehensive curriculum. For instance, the critical curriculum contains topics that provide the opportunity to translate the ABCDE principles of trauma management into practice. Furthermore, a post in the A&E department provides the surgical trainee with significant exposure to the management of the polytrauma patient and to the management of other acute general surgical, urological and orthopaedic conditions. By presenting better educational programs and by reducing the non-medical tasks a trainee has to deal with, the education of surgical trainees during A&E attachment can be improved.


Retroviral transduction of T-cell antigen receptor beta-chain and myc genes.
Support for multistage models of oncogenesis has been provided by several highly leukaemogenic retrovirus isolates that have transduced more than one host cell gene. Where functional studies have been performed, these retroviral oncogenes show synergy for in vitro transformation and leukaemogenesis. In naturally occurring feline leukaemias associated with feline leukaemia virus (FeLV), retroviral transduction of myc is a frequent oncogenic mechanism. But evidence suggesting that the FeLV v-myc genes might be insufficient for leukaemogenesis was provided by the latency (12 weeks) and clonality of FeLV/v-myc-induced tumours and the absence of demonstrable in vitro transformation by these viruses. In the search for secondary leukaemogenic events in FeLV/v-myc tumours, we have identified a case of FeLV transduction of a T-cell antigen receptor beta-chain gene. The proviruses carrying this gene (which we have named v-tcr) were a separate population from those carrying v-myc. In its normal role, the T-cell receptor beta-chain forms part of a multimeric complex involved in antigen recognition and T-cell activation. We suggest that v-tcr is a novel viral oncogene which assisted v-myc in the genesis of a naturally occurring case of thymic lymphosarcoma.


[Fundamental and applied aspects of neuroendocrine regulation of pro- and eukaryote interactions].
The paper presents the results of light, atomic-force, and electron microscopic studies of prokaryotes (various Staphylococcus aureus strains) and eukaryotes (Rat digestive and respiratory cells and tissues) in in vivo and in vivo interactions. It is concluded that hypothalamic nonapeptides play a modulating role in the persistence and symbiotic relations in the bacterium-host system and regulate cellular and tissue homeostasis through reparative histogenesis.


The impact of primary care reform on health system performance in Canada: a systematic review.
We aimed to synthesize the evidence of a causal effect and draw inferences about whether Canadian primary care reforms improved health system performance based on measures of health service utilization, processes of care, and physician productivity. We searched the Embase, PubMed and Web of Science databases for records from 2000 to September 2015. We based our risk of bias assessment on the Grading of Recommendations Assessment, Development and Evaluation guidelines. Full-text studies were synthesized and organized according to the three outcome categories: health service utilization, processes of care, and physician costs and productivity. We found moderate quality evidence that team-based models of care led to reductions in emergency department use, but the evidence was mixed for hospital admissions. We also found low quality evidence that team-based models, blended capitation models and pay-for-performance incentives led to small and sometimes non-significant improvements in processes of care. Studies examining new payment models on physician costs and productivity were of high methodological quality and provided a coherent body of evidence assessing enhanced fee-for-service and blended capitation payment models. A small number of studies suggested that team-based models contributed to reductions in emergency department use in Quebec and Alberta. Regarding processes of diabetes care, studies found higher rates of testing for blood glucose levels, retinopathy and cholesterol in Alberta's team-based primary care model and in practices eligible for pay-for-performance incentives in Ontario. However pay-for-performance in Ontario was found to have null to moderate effects on other prevention and screening activities. Although blended capitation payment in Ontario contributed to decreases in the number of services delivered and patients seen per day, the number of enrolled patients and number of days worked in a year was similar to that of enhanced fee-for-service practices.


Characterizing social environment's association with neurocognition using census and crime data linked to the Philadelphia Neurodevelopmental Cohort.
The contribution of 'environment' has been investigated across diverse and multiple domains related to health. However, in the context of large-scale genomic studies the focus has been on obtaining individual-level endophenotypes with environment left for future decomposition. Geo-social research has indicated that environment-level variables can be reduced, and these composites can then be used with other variables as intuitive, precise representations of environment in research. Using a large community sample (N = 9498) from the Philadelphia area, participant addresses were linked to 2010 census and crime data. These were then factor analyzed (exploratory factor analysis; EFA) to arrive at social and criminal dimensions of participants' environments. These were used to calculate environment-level scores, which were merged with individual-level variables. We estimated an exploratory multilevel structural equation model (MSEM) exploring associations among environment- and individual-level variables in diverse communities. The EFAs revealed that census data was best represented by two factors, one socioeconomic status and one household/language. Crime data was best represented by a single crime factor. The MSEM variables had good fit (e.g. comparative fit index = 0.98), and revealed that environment had the largest association with neurocognitive performance (β = 0.41, p < 0.0005), followed by parent education (β = 0.23, p < 0.0005). Environment-level variables can be combined to create factor scores or composites for use in larger statistical models. Our results are consistent with literature indicating that individual-level socio-demographic characteristics (e.g. race and gender) and aspects of familial social capital (e.g. parental education) have statistical relationships with neurocognitive performance.


Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent.
Liver injury is estimated by serum alanine aminotransferases (ALT) levels in experimental animal models. Laboratories use various techniques to measure ALT levels including assay reagents and chemistry analyzers. VetScan VS2 (VS2) is widely used in veterinary clinics and research laboratories for highly reproducible, convenient and effective testing. Alternatively, ALT liquid reagent is used by laboratories to estimate liver injury in animal studies. The aim of this study was to perform comparative analyses of data obtained from these two assays in two different animal models. In this study, we used two different mouse models and compared the ALT levels measured using VetScan VS2 chemistry analyzer and ALT liquid reagent. Immunohistochemical analysis of hepatic tissue was also performed to document liver pathology. The first model is a high fat diet feeding model that results in a mild hepatic steatosis (fat accumulation in the liver) without elevation of ALT levels. For a severe liver injury model, we employed a hepatotoxin-induced liver injury model (carbon tetrachloride, CCl4), which leads to the development of hepatic fibrosis and very high ALT levels. VetScan VS2 and ALT reagent gave different values of ALT for all animal groups. However, linear regression analysis showed a significantly high association between ALT levels obtained by VS2 and ALT liquid reagent in a high-fat feeding model with no liver injury. For the CCl4 induced liver injury model, serum dilution (5 and 10 times) was performed to obtain accurate results with ALT reagent. ALT levels acquired from both techniques showed a close association. Interestingly, this correlation was closer when serum was diluted 5 fold. This study demonstrates that both methods give similar results when evaluating liver injury in animal studies. However, the serum dilution factor is critical for severe liver injury assessment when using ALT reagent and requires some optimization. In this regard, VetScan VS2 is easier to use and gives comparable results.


A method of estimating infant deaths in Korea.
"The goal of this project was to develop a new method for estimating infant deaths in [South] Korea. An attempt was made to collect information on real infant death cases by using...medical insurance benefit data and by conducting a medical facilities survey, which allows us to [trace] back the fate of the births from the delivery. Another strategy employed was the gathering of information on infant deaths from the various existing sources and integrating them into one set after adjusting for overlapping cases among the sources." (SUMMARY IN KOR)


Time correlation of commitment to calcium-induced apoptosis and terminal differentiation in human ectocervical keratinocytes in suspension cultures.
The terminal differentiation of epithelial keratinocytes has been proposed to be a specialized form of programmed cell death (apoptosis). We examined the time correlation of apoptosis and terminal differentiation by human ectocervical keratinocytes in a suspension culture that induces either of these events in epithelial cells. We found that a loss of cell anchorage did not result in the immediate onset of apoptotic DNA degradation but sensitized the cells to that triggered by calcium. This susceptibility appeared in parallel with the irreversible loss of growth potential and the accumulation of involucrin, suggesting that the ectocervical keratinocytes in suspension become competent to calcium-inducible apoptosis as they committed to terminal differentiation. Cycloheximide, which inhibited the calcium induction of DNA fragmentation, was also inhibitory to terminal differentiation. These correlations support the notion that terminal differentiation of keratinocytes couples with apoptosis. Apoptosis seemed to be independent of p53 because it was down-regulated in suspension cultures of ectocervical keratinocytes.


Intraosseous anesthesia using a computer-controlled system during non-surgical periodontal therapy (root planing): Two case reports.
Local anesthesia is administered to control pain, but it may induce fear and anxiety. Root planing is a non-surgical periodontal therapy; however, when it is performed in an extensive manner, some tissue removal is inevitable. Notably, this removal may be so painful that local anesthesia is required to be administered to the area scheduled for the treatment. Although patients tend to accept root planing easily, they frequently express a fear of local anesthesia. Intraosseous anesthesia (IA) is an intraosseous injection technique, whereby local anesthetic is injected into the cancellous bone supporting the teeth. A computer-controlled IA system (CIAS) exhibits multiple benefits, such as less painful anesthesia, reduced soft tissue numbness, and the provision of palatal or lingual, as well as buccal, anesthesia via single needle penetration. In this report, we present two cases of root planing that were performed under local anesthesia, using a CIAS.


Chemical Vapor Deposition Synthesis and Terahertz Photoconductivity of Low-Band-Gap N = 9 Armchair Graphene Nanoribbons.
Recent advances in bottom-up synthesis of atomically defined graphene nanoribbons (GNRs) with various microstructures and properties have demonstrated their promise in electronic and optoelectronic devices. Here we synthesized N = 9 armchair graphene nanoribbons (9-AGNRs) with a low optical band gap of ∼1.0 eV and extended absorption into the infrared range by an efficient chemical vapor deposition process. Time-resolved terahertz spectroscopy was employed to characterize the photoconductivity in 9-AGNRs and revealed their high intrinsic charge-carrier mobility of approximately 350 cm2·V-1·s-1.


Laparoscopic prostatectomy: where do we stand?
Laparoscopic radical prostatectomy is an effective treatment for localized prostate cancer. This cost-intensive and technically demanding operation currently takes longer than the standard open procedures, but with increasing experience, it is eventually associated with lower costs and is nearly as fast. As more urologists gain such experience, the laparoscopic approach may challenge the standard approaches.


Clinical presentation and survival in a population-based cohort of infants with gastroschisis in Utah, 1997-2011.
Typically gastroschisis is considered an isolated birth defect; however, other major malformations are reported to occur in 5-35% of cases depending on inclusion criteria. This study evaluated the associated malformations, small for gestational age, and survival among a clinically well-characterized population-based gastroschisis cohort, delivered from 1997-2011. We used data from Utah's statewide population-based surveillance system, which monitors major structural birth defects among all pregnancy outcomes (i.e., live births, stillbirths, pregnancy terminations, and miscarriages). Of the initial 387 gastroschisis cases, we excluded 51 (13.2%) for the following reasons: inadequately described or macerated fetuses, part of a specific malformation complex or sequence (limb-body wall complex, amniotic band sequence, or a severe form of abdominoschisis), leaving a study sample of 336 clinically confirmed cases. Gastroschisis was isolated non-syndromic in 284 cases (84.5%). One case was syndromic (trisomy 16; 0.3%) and the remaining 51 (15.2%) were classified as multiple: one unrelated major malformation (27; 52.9%); two or more unrelated major malformation or one major with multiple minor anomalies or mild malformations (6; 11.8%); ≥ one distinctive minor anomaly or mild malformation (13; 25.5%); amyoplasia (5; 1.5%). Of the liveborn infants, 63.3% were preterm (delivered at <37 weeks of gestation) and 21.8% were small for gestational age (SGA). SGA was more common in males (38.8%) than females (16%) (P = 0.008). Overall first year survival was high (95.6%); however, preterm infants with congenital intestinal atresia had the highest mortality (13.8%). The high proportion of isolated cases (84.5%) in gastroschisis is similar to that observed in many other phenotypes and not unique to gastroschisis. Because one in every six infants with gastroschisis had a major unrelated malformation, additional malformations should be sought in every newborn with gastroschisis. Infant mortality was low overall but still a significant concern in affected preterm infants with associated congenital intestinal atresia.


Power and sample size for stratified prospective studies using the score method for testing relative risk.
We derive the asymptotic power function of the score test for detecting a common relative risk greater than unity from multiple 2 x 2 tables and formulate methods of sample size determination for use when designing stratified prospective studies. The stratified score test is more efficient than the unstratified test when the latter is unbiased.


Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl.
Gelastic seizures (GS) are typically associated with hypothalamic hamartomas and present during childhood. However it is now known that GS can be found in focal epilepsies arising from other regions in the brain, including mesial and neocortical frontal, temporal and parietal regions. GS have rarely been described as the presenting manifestation of New Onset Refractory Status Epilepticus (NORSE). In this article we describe a previously healthy 3-year-old who presented with an explosive onset of GS that were refractory to multiple anti-seizure medications. These seizures arose from the right frontal region. An extensive metabolic and immunological evaluation was negative. Her brain magnetic resonance imaging (MRI) was negative, however the Positron Emission Tomography (PET) scan showed a hypermetabolic region in the right frontal inferior gyrus. She underwent a depth electrode evaluation that revealed a widespread irritative zone involving the PET "lesion" as well as mesial and neocortical regions in the right frontal lobe. The seizure onset zone was widespread and non-localizable. However the GS were associated with a clear ictal epileptiform discharge on invasive EEG arising from the depth of the superior frontal gyrus, which was not overlapping with the PET hypermetabolic region. She underwent a right frontal lobectomy sparing the primary motor region in the pre-central gyrus. She has remained seizure free for 15 months since. The pathological analysis showed focal cortical dysplasia type II in the region of the PET scan hypermetabolism. This case expands the clinical spectrum of GS to include cases of NORSE. Additionally the case highlights the role of resective surgery in GS presenting as NORSE and the potentially excellent outcome that can be achieved by early intervention.


Acute epiglottitis; a clinical, bacteriological and serological study.
25 patients, 15 children and 10 adults, with the clinical diagnosis of acute epiglottitis were studied. Patients severely ill on admission, 13 children and 1 adult, were immediately treated with tracheotomy and antibiotics; the remaining patients with antibiotics only. Haemophilus influenzae type b was the causative organism in all children and in 3 adults. One adult had a Diplococcus pneumoniae infection. No pathogens were isolated from the 6 remaining patients. Four of the children developed H. influenzae type b meningitis. All patients recovered. Anti-b antibodies were not demonstrable in any initial serum sample while agglutinating anti-b antibodies were found in subsequent samples (indirect hemagglutination). All patients with a type b infection had already initially precipitating anti-O antibodies against their own strain, and in most cases complement-fixing anti-O antibodies (mixed H. influenzae O antigen) with rising titers in subsequent serum samples. A possible connection between the presence of anti-O antibodies initially and the development of the acute epiglottitis is discussed.


Long-term effects of medication for opioid use disorder in children.
Opioid maintenance therapy in pregnant patients can result in children born with neonatal abstinence syndrome (NAS). These infants are at high risk for poor school performance, unemployment, and criminal activity because they never reach the neurocognitive levels of their peers. This article discusses the neurocognitive development consequences of medicated opioid use disorder on infants and children and methods to help them reach their potential into adulthood.


[Features of conditioned alimentary instrumental reflexes in rats differing in the nature of their behavior in response to painful stimulation of conspecifics].
Groups of rats preliminary classified by their avoiding (A) or not avoiding (B) the closed space at hearing the cries of an other painfully stimulated animal (by Simonov 's method) significantly differed by parameters of an alimentary instrumental conditioned reflex. The group A, as compared to the group B, was characterized by short latencies, high afferent generalization and relative independence of latency of the alimentary reflex on the state of satiation or hunger. Such properties are supposed to be connected with individually different intensity of alimentary motivation (strong in A and weak in B) limited by a system of inborn passive defensive reactions.


Interaction of basic compounds with coated vesicles.
The effect of poly- and dibasic amines, including chloroquine and quinacrine, on the dissociation of coated vesicles at pH 7.4 in 0.01 M 2-(N-morpholino)ethanesulfonic acid has been evaluated by light scattering and sucrose gradient centrifugation. The degree of inhibition of dissociation by the polybases is proportional to the number of amine groups in each compound. However, very little difference in effectiveness was found in a series of dibasic compounds, NH2(CH2)2-5NH2. Chloroquine and quinacrine contain dibasic aliphatic chains as well as aromatic ring systems. These two antimalarials are more effective in inhibiting dissociation of coated vesicles than the dibasic aliphatic amines. The ring systems therefore appear to be contributing, independently, to the free energy of stabilization of the coat structure of coated vesicles. It is suggested that the interaction of poly- or dibasic compounds with clathrin or coated vesicles could influence the turnover of ligands in receptor-mediated endocytosis.


Gastric emptying of indigestible solids--a rat model.
The effects of ingestion of digestion of digestible solids and liquids on gastric emptying of indigestible solids were studied. Thirty rats were allocated to one of five groups; in four groups, rats had been fasted for 24 h before the experiment, whereas in the fifth group, they had not been fasted. In all groups, ten steel balls (1.0 mm in diameter) were inserted through an orogastric cannula into the stomach under brief halothane anesthesia. In the four groups of fasted rats, one of the following substance was then given into the stomach: (1) 0.5 g digestible solids; (2) 1.0 ml saline; (3) 1.0 ml contrast medium (45% wv sodium diatrizoate); (4) no substance (control group). Three hours later, the number of balls which had passed into the intestine was counted. Ingestion of 0.5 g meal in fasted rats significantly delayed gastric emptying of steel balls (P < < 0.001), whereas there was no difference in gastric emptying of steel balls between fasted rats and fully fed rats. Ingestion of the contrast medium (P < < 0.001), but not that of saline, significantly delayed the emptying of the balls. Therefore, ingestion of digestible solids or liquids may delay gastric emptying of indigestible solids. Clinical implications of gastric emptying of indigestible solids are discussed.


PREVALENCE AND TIME TRENDS OF MYOPIA IN CHILDREN AND ADOLESCENTS IN CHINA: A Systemic Review and Meta-Analysis.
To estimate prevalence, associated factors, and time trends of myopia in Chinese children and adolescents. We searched PubMed, EMBASE, and Web of Science for studies examining the prevalence of myopia in children and adolescents aged 3 years to 19 years in China before October 2018. We pooled the prevalence and associated factors for myopia and estimated time trends. In 22 eligible studies including 192,569 individuals, the pooled prevalence (95% confidence interval [CI]) of myopia and high myopia in the study period from 1998 to 2016 was 37.7% (95% CI: 23.5-52.0%) and 3.1% (95% CI: 1.2-5.0%), respectively, with higher odds for girls than boys (myopia: odds ratio: 1.29; 95% CI: 1.14-1.46; P < 0.001; high myopia: odds ratio: 1.37; 95% CI: 1.05-1.78; P = 0.02) and with higher prevalences for urban areas than rural regions (myopia: 48.8% [95% CI: 32.3-65.3] vs. 31.9% [95% CI: 20.4-43.3; P < 0.001]). The pooled prevalence of myopia and high myopia increased from 4.7% (95% CI: 2.5-6.9) and 0.2% (95% CI: 0.0-0.5), respectively, in <7-years-olds to 56.2% (95% CI: 29.8-82.5) and 15.1% (95% CI: 6.4-23.8), respectively, in 16- to 18-year-olds. Myopic refractive error increased with older age (P < 0.001), female gender (P < 0.001), and study year (P = 0.003). Studies performed after 2013 showed a prevalence of myopia and high myopia in the 16- to 18-year-olds of 84.8% (95% CI: 84.4-85.2%) and 19.3% (95% CI: 18.6-20.2%), respectively. Assuming a further linear relationship with the study year, myopia prevalence in 2050 among children and adolescents aged 3 years to 19 years would be estimated to be about 84%. The marked rise in high myopia prevalence among adolescents in China may be of importance for high myopia as risk factor for irreversible vision loss in Chinese adults in the future.


Measuring and modeling vocal source-tract interaction.
The quality of synthetic speech is affected by two factors: intelligibility and naturalness. At present, synthesized speech may be highly intelligible, but often sounds unnatural. Speech intelligibility depends on the synthesizer's ability to reproduce the formants, the formant bandwidths, and formant transitions, whereas speech naturalness is thought to depend on the excitation waveform characteristics for voiced and unvoiced sounds. Voiced sounds may be generated by a quasiperiodic train of glottal pulses of specified shape exciting the vocal tract filter. It is generally assumed that the glottal source and the vocal tract filter are linearly separable and do not interact. However, this assumption is often not valid, since it has been observed that appreciable source-tract interaction can occur in natural speech. Previous experiments in speech synthesis have demonstrated that the naturalness of synthetic speech does improve when source-tract interaction is simulated in the synthesis process. The purpose of this paper is two-fold: 1) to present an algorithm for automatically measuring source-tract interaction for voiced speech, and 2) to present a simple speech production model that incorporates source-tract interaction into the glottal source model. This glottal source model controls: 1) the skewness of the glottal pulse, and 2) the amount of the first formant ripple superimposed on the glottal pulse. A major application of the results of this paper is the modeling of vocal disorders.


Pyrrolidinoindoline Alkaloids from Psychotria colorata1
Fractionation of an alkaloid extract of Psychotria colorata flowers led to the isolation of six alkaloids, identified by UV, 1D and 2D NMR, and MS as (-)-calycanthine, isocalycanthine, (+)-chimonanthine, hodgkinsine, quadrigemine C, and a new alkaloid (1), whose structure was deduced by X-ray analysis to be (8-8a),(8'-8'a)-tetradehydroisocalycanthine 3a(R), 3'a(R).


Evidence of neuropeptide bivalency in the interaction of substance P with cerebroside sulfate.
A precipitin effect has been observed with mixtures of cerebroside sulfate and the neuropeptide substnace P. This phenomenon is attributed to multivalency of the lipid due to its existence in micellar form, and to bivalency of substance P. One of those neuropeptide sites is almost certainly the basic residue(s) located at the N-terminal of substance P, whereas the hydrophobic residues at the C-terminus are suggested as candidates for the other site on the basis of turbidimetric, circular dichroic, and fluorometric studies. An intrinsic association constant of 3.6 x 10(4)M-1 has been obtained from the cerebroside sulfate concentration associated with maximal turbidity of mixtures containing a fixed concentration of the neuropeptide.


Treatment of metal-contaminated water using bacterial sulfate reduction: results from pilot-scale reactors.
Simple anaerobic reactors were installed to treat metal-contaminated water in an underground coal mine and at a smelting residues dump in Pennsylvania. The reactors consisted of barrels and tanks filled with spent mushroom compost, within which bacterial sulfate reduction became established. Concentrations of Al, Cd, Fe, Mn, Ni, and Zn were typically lowered by over 95% as contaminated water flowed through the reactors. Cadmium, Fe, Ni, and some Zn were retained as insoluble metal sulfides following their reaction with bacterially generated H(2)S. Aluminum, Mn, and some Zn hydrolyzed and were retained as insoluble hydroxides or carbonates. Reactor effluents were typically circumneutral in pH and contained net alkalinity. The principal sources of alkalinity in the reactors were bacterial sulfate reduction and limestone dissolution. This article examines the chemistry of the reactor systems and the opportunities for enhancing their metal-retaining and alkalinity-generating potential.


Unhealthy Dietary Habits and Obesity: The Major Risk Factors Beyond Non-Communicable Diseases in the Eastern Mediterranean Region.
There are 22 countries in the Eastern Mediterranean Region (EMR) expanding from Morocco in the west to Pakistan and Afghanistan in the east, containing a population of 725,721 million in 2020. In the previous 30 years, the illness burden in the EMR has transmitted from communicable diseases to non-communicable diseases such as diabetes, cardiovascular diseases, and cancer. In 2019, cardiovascular mortality in the EMR was mostly attributed to ischemic heart disease, the first reason for mortality in 19 countries in the region. Stroke was the second reason for death in nine countries followed by diabetes, which was ranked as the second reason for death in two countries. The prominent nutrition-related NCDs risk factors in EMR include obesity, hypertension, high fasting plasma glucose, and upregulated unhealthy diet consumption. Most of the EMR population are unaware of their NCDs risk factor status. These risk factors, even if treated, are often poorly controlled, therefore, inhibiting their existence by changing the lifestyle to proper dietary habits and sufficient physical activity is mandatory. In this review, the epidemiology and nutrition-related risk factors of NCDs in the EMR will be discussed and illustrated, aiming to scale up action and support decision-makers in implementing cost effective strategies to address obesity and NCDs prevention and management in the region.


The purine derivative PI-55 blocks cytokinin action via receptor inhibition.
One of several potential approaches to study mechanisms of action of biologically active compounds is to develop their agonists and antagonists. In the present study, we report the identification of the first known molecule antagonizing the activity of the plant hormone cytokinin at the receptor level. This compound, 6-(2-hydroxy-3-methylbenzylamino)purine, designated PI-55 in the present study, is structurally closely related to cytokinin 6-benzylaminopurine, but substitutions at specific positions of the aromatic side chain strongly diminished its cytokinin activity and conferred antagonistic properties. PI-55 competitively inhibited the binding of the natural ligand trans-zeatin to the Arabidopsis cytokinin receptors cytokinin response 1 (CRE1)/Arabidopsis histidine kinase (AHK) 4 and AHK3 and repressed induction of the cytokinin response gene ARR5:GUS. Genetic analysis revealed that CRE1/AHK4 is the primary target of PI-55. Cytokinin bioassays also demonstrated the anticytokinin effect of PI-55 in several other species. Furthermore, we show that PI-55 accelerated the germination of Arabidopsis seeds and promoted the root growth and formation of lateral roots, thus phenocopying the known consequences of a lowered cytokinin status and demonstrating its potential to inhibit cytokinin perception in planta. PI-55 is the first example for the targeted development of a cytokinin antagonist and represents an initial step for the preparation of cytokinin antagonists with broad activity and reduced agonistic properties.


Effects of land-use change in the Amazon on precipitation are likely underestimated.
The Amazon forest enhances precipitation levels regionally as trees take up water from the soil and release it back into the atmosphere through transpiration. Therefore, land-use changes in the Amazon affect precipitation patterns but to what extent remains unclear. Recent studies used hydrological and atmospheric models to estimate the contribution of tree transpiration to precipitation but assumed that precipitation decreases proportionally to the transpired portion of atmospheric moisture. Here, we relaxed this assumption by, first, relating observed hourly precipitation levels to atmospheric column water vapor in a relatively flat study area encompassing a large part of the Amazon. We found that the effect of column water vapor on hourly precipitation was strongly nonlinear, showing a steep increase in precipitation above a column water vapor content of around 60 mm. Next, we used published atmospheric trajectories of moisture from tree transpiration across the whole Amazon to estimate the transpiration component in column water vapor in our study area. Finally, we estimated precipitation reductions for column water vapor levels without this transpired moisture, given the nonlinear relationship we found. Although loss of tree transpiration from the Amazon causes a 13% drop in column water vapor, we found that it could result in a 55%-70% decrease in precipitation annually. Consequences of this nonlinearity might be twofold: although the effects of deforestation may be underestimated, it also implies that forest restoration may be more effective for precipitation enhancement than previously assumed.


Defining operational taxonomic units using DNA barcode data.
The scale of diversity of life on this planet is a significant challenge for any scientific programme hoping to produce a complete catalogue, whatever means is used. For DNA barcoding studies, this difficulty is compounded by the realization that any chosen barcode sequence is not the gene 'for' speciation and that taxa have evolutionary histories. How are we to disentangle the confounding effects of reticulate population genetic processes? Using the DNA barcode data from meiofaunal surveys, here we discuss the benefits of treating the taxa defined by barcodes without reference to their correspondence to 'species', and suggest that using this non-idealist approach facilitates access to taxon groups that are not accessible to other methods of enumeration and classification. Major issues remain, in particular the methodologies for taxon discrimination in DNA barcode data.


[Assessment of percutaneous vertebroplasty and percutaneous kyphoplasty for treatment of senile osteoporotic vertebral compression fractures].
To investigate the clinical effects and safety of vertebroplasty and kyphoplasty for the senile osteoporotic vertebral compression fractures. From December 2004 to June 2008, 28 patients (40 vertebrae) with osteoporotic vertebral compression fractures were treated with percutaneous vertebroplasty (PVP group), there were 11 males (14 vertebrae) and 17 females (26 vertebrae), with an average age of 72 years (ranged, 70 to 91 years). The fracture site of vertebral body was from T5 to L5. Other 31 patients (43 vertebrae) were treated with percutaneous kyphoplasty (PKP group), there were 13 males (18 vertebrae) and 18 females (25 vertebrae), with an average age of 74 years (ranged, 70 to 92 years). The fracture site of vertebral body was from T4 to L5. Theapeutic effects of all the patients were observed after operation, the item included visual analog scale (VAS), Oswestry score, Cobb angle, the height of anterior and middle column vertebra, and the incidence of cement leakage. There was significant decrease in VAS score and Oswestry score after operation in both groups, there was significant difference between preoperative and postoperative (P < 0.01). There was no significant difference in VAS score and Oswestry score between two groups (P > 0.05). There was no significant difference in Cobb angles and the height of anterior and middle column vertebra between two groups before and after operation (P > 0.05). Among them, there were 3 vertebrae cement leakage in PVP group (7.5%) and 2 in PKP group (4.7%), but no clinical sympton occurred. There was no significant difference in the incidence of cement leakage between two groups (P > 0.05). Vertebroplasty and kyphoplasty are safe and effective methods in treating senile osteoporotic vertebral compression fractures, which can restore the height of fractured vertebra, relieve pain and improve function as well as minimize the incidence of cement leakage.


Glycogen: Biosynthesis and Regulation.
Glycogen accumulation occurs in Escherichia coli and Salmonella enterica serovar Typhimurium as well as in many other bacteria. Glycogen will be formed when there is an excess of carbon under conditions in which growth is limited because of the lack of a growth nutrient, e.g., a nitrogen source. This review describes the enzymatic reactions involved in glycogen synthesis and the allosteric regulation of the first enzyme, ADP-glucose pyrophosphorylase. The properties of the enzymes involved in glycogen synthesis, ADP-glucose pyrophosphorylase, glycogen synthase, and branching enzyme are also characterized. The data describing the genetic regulation of the glycogen synthesis are also presented. An alternate pathway for glycogen synthesis in mycobacteria is also described.


Discovery and Bioevaluation of Novel Pyrazolopyrimidine Analogs as Competitive Hsp90 Inhibitors Through Shape-Based Similarity Screening.
Hsp90 as a promising therapeutic target for the treatment of cancer has received great attention. Many Hsp90 inhibitors such as BIIB021 and CUDC-305 have been in clinical. In this paper shape-based similarity screening through ROCS overlays on the basis of CUDC-305, BIIB021, PU-H71 and PU-3 were performed to discover HSP90 inhibitors. A set of 19 novel pyrazolopyrimidine analogues was identified and evaluated on enzyme level and cell-based level as Hsp90 inhibitors. The compound HDI4-04 with IC50 0.35 µM in the Hsp90 ATP hydrolysis assay exhibited potent cytotoxicity against five human cancer cell lines. Western blot analysis and Hsp70 luciferase reporter assay further confirmed that HDI4-04 targeted the Hsp90 protein folding machinery. And according to the biological assay, the SAR was discussed and summarized, which will guide us for further optimization of these compounds.


Partial desalination and concentration of glyphosate liquor by nanofiltration.
Partial desalination and concentration of glyphosate liquor by nanofiltration under different operation modes were investigated experimentally in this study. These operation modes were direct nanofiltration, diafiltration, dilute-diafiltration and interval washing-nanofiltration. The four different operation modes were evaluated and compared in terms of glyphosate recovery and NaCl removal. Diafiltration and dilute-diafiltration performed better than direct nanofiltration. The glyphosate loss was between 11.5% and 18.8% when the dilution factor varied from 0.4 to 0.8. Interval washing-nanofiltration alleviated the concentration polarization and membrane fouling to a certain extent. Dilute-diafiltration may be the best operation mode in terms of glyphosate recovery, salt removal and cost.


Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial.
Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial. Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870. Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial. This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision. Cancer Research UK and the Australian National Health and Medical Research Council.


Low temperature solution-processed high performance photodiode based on Si-ZnO core-shell structure.
Radial heterojunction photodiodes based on a silicon nanowire arrays (SiNWs)-zinc oxide (ZnO) core-shell structure is demonstrated in this report. The heterojunction can be constructed by spin-coating ZnO nanoparticles onto SiNWs and a low temperature post-annealing process (<270 °C). The photodiode displays typical diode rectifying characteristics with an ideality factor of as low as 1.28, and shows an excellent photoresponse in both visible and near infrared regions in which a peak value of 0.54 A/W at zero bias was attained. The sensitivity is superior to that of previously reported devices fabricated with vacuum-deposition methods. In contrast, the planar silicon-ZnO junction only displays the peak photoresponsivity of 0.34 A/W. The superior performance of radial junction is ascribed to the highlight-harvesting capability, large interfacial area and efficient charge carrier collection arising from the core (SiNWs)-shell (ZnO) structure. Here, high temperature processes are dispensable by using facile solution-processed techniques, which avoid thermal minority lifetime degradation of silicon and simplify the fabrication process of the photodiodes.


Enhancing Exercise Responsiveness across Prediabetes Phenotypes by Targeting Insulin Sensitivity with Nutrition.
Exercise is a cornerstone therapy for chronic diseases related to multiorgan insulin resistance. However, not all individuals show the anticipated improvement in insulin sensitivity following exercise and these individuals are considered exercise resistant. Caloric restriction is an approach to enhance the effect of exercise on increasing peripheral and hepatic insulin sensitivity, as replenishing expended calories blunts these benefits. Alternatively, restricting carbohydrate intake, independent of energy balance, following exercise provides an additive effect on peripheral insulin sensitivity when compared to refeeding carbohydrate. Although carbohydrate composition modulates insulin sensitivity, few have studied effects of low glycemic index or whole-grain diets following exercise across prediabetes phenotypes on insulin sensitivity. Herein, we propose the novel hypothesis that the combination of individualized nutrition therapy and exercise should be based on the clinical pathology of prediabetes to overcome exercise resistance and improve responsiveness in people at risk for type 2 diabetes and cardiovascular disease.


CGH-targeted linkage analysis reveals a possible BRCA1 modifier locus on chromosome 5q.
Women with germline mutations in BRCA1 have a greatly elevated risk of breast and ovarian cancer. However, considerable variation in the degree of breast cancer risk associated with a BRCA1 mutation has been observed, suggesting that modifiers of BRCA1 penetrance may exist. We hypothesized that the modifier genes might be located in regions of allelic imbalance in the tumors of BRCA1 mutation carriers, as have been reported on chromosomes 4p, 4q and 5q. In order to determine whether novel genetic modifiers of BRCA1-associated breast cancer penetrance in these regions exist, we used non-parametric linkage analysis methods to determine whether allele sharing of chromosomes 4p, 4q and 5q was observed preferentially within BRCA1 mutation families in women with BRCA1 mutations and breast cancer. No significant linkage on chromosome 4p or 4q was observed associated with breast cancer risk in BRCA1 mutation carriers. However, we observed a significant linkage signal at D5S1471 on chromosome 5q (P = 0.009) in all the families analyzed together. The significance of this observation increased in the subset of families with an average of breast cancer diagnosis less than 45 years (P = 0.003). These results suggest the presence of one or more genes on chromosome 5q33-34 that modify breast cancer risk in BRCA1 mutation carriers. The approach described here may be utilized to identify penetrance modifiers in other autosomal dominant syndromes.


Comparison of two flow generators with a noninvasive ventilator to deliver continuous positive airway pressure: a test lung study.
To compare the performance of two continuous flow generators with a ventilator designed for noninvasive positive pressure ventilation (NPPV) to deliver continuous positive airway pressure (CPAP). The performance of flow generators using different oxygen pressure supplies was also compared. Experimental study using a mechanical lung model in a university research laboratory. Two flow generators supplied at 100, 200, and 300 kPa and an NPPV ventilator were compared at CPAP of 5, 10, and 15 cmH2O in: (a) area under the adjusted CPAP level during inspiration, (b) capacity to attain the preset CPAP, and (c) tidal volume. The NPPV ventilator attained the preset CPAP better than flow generators, but its area under adjusted CPAP was similar to or higher than that of flow generators when these were adjusted to their better pressure supply. Both flow generators had better performance with an output flow around 100 l/min, which was achieved at 100 kPa with one flow generator and 300 with the other. Flow generators and the NPPV ventilator generated similar tidal volumes. Flow generators performance showed large variations among different devices and oxygen pressure supplies. Adjusted to their better pressure supply, flow generators had a similar or better capacity to maintain the CPAP level, but the NPPV ventilator was more reliable to attain the preset CPAP. Flow generators could be an alternative to provide CPAP in low-income areas, usually with scarce medical equipment availability.


[Theoretical studies on stress protection in fractures treated by osteosynthesis].
Using a simple model geometry the effect of stress protection in a bone caused by combination with a metal plate is studied. It is found that no global stress protection exists in any case. The stresses in the bone can be higher than in the homogeneous bone without any reinforcement. Therefore, a consideration of any special type of implantation should be done.


Alcohol and alkalosis enhance excystation of Opisthorchis viverrini metacercariae.
The northeastern region of Thailand has long been known as an endemic area of the human liver fluke infection which is caused by Opisthorchis viverrini. Humans are infected by ingestion of uncooked cyprinoid fish in traditional dishes such as "koi-pla," "pla-som," "pla-jom," and "pla-ra." To date, the prevalence of this parasite infection remains high because of cultural behavior and local beliefs. The popular misunderstanding among people in this area is that alcohol, lemon juice, and fish sauce can kill the parasites. Thus, they believe that they can eat raw fish without the risk of infection. This study attempts to clarify the effects of ethyl alcohol and acidosis-alkalosis on O. viverrini metacercariae excystation. Metacercariae of O. viverrini were obtained from infected cyprinoid fish in a natural reservoir. Most metacercariae were obtained from small cyprinoid fish. Metacercariae were divided into three experimental groups and were treated with solutions containing four different concentrations of ethyl alcohol, four different concentrations of salt, and a range of acidic/basic pH. Metacercariae excystation was observed at the assigned times, and the data were then analyzed. Salt had no effect on excystation. Interestingly, the optimal conditions for O. viverrini excystation were pH 9 and 25 % ethyl alcohol. The present study suggests that raw fish should not be eaten while drinking alcohol or when consuming other ingredients with pH 9, because both alcohol and pH 9 could induce O. viverrini metacercariae excystation, leading to the early development of parasites in the hepatobiliary system.


Biomechanical Weakening of Different Re-treatment Options After Small Incision Lenticule Extraction (SMILE).
To determine the corneal weakening induced by different re-treatment options after small incision lenticule extraction (SMILE) and investigate the potential of corneal cross-linking (CXL) to reestablish the original corneal stress resistance. A total of 96 freshly enucleated porcine corneas were used. The initial refractive correction was defined to be -11.00 diopters (D) and the required enhancement to be -3.00 D. Three different re-treatment options were analyzed: -3D Re-SMILE, -3D photorefractive keratectomy (PRK) on top of the SMILE cap, and cap-to-flap conversion and -3D excimer ablation on the stromal bed (LASIK). The control condition did not receive any treatment. Subsequently, accelerated CXL (9 mW/cm2, 10 min) was performed in two groups with currently common enhancement techniques: following cap-to-flap conversion (-3D LASIK enhancement) and in controls. Biomechanical properties were measured with stress-strain extensometry ranging from 1.27 to 12.5 N. The Re-SMILE and PRK enhancement did not significantly reduce the overall elastic modulus of the cornea compared to controls (24.7 ± 2.23 and 22.7 ± 2.61 versus 23.8 ± 3.35 MPa, P ≥ .176), whereas LASIK enhancement did (22.2 ± 3.37 MPa, P = .048). CXL treatment significantly increased the elastic modulus compared to all non-cross-linked conditions (P ≤.001). Refractive surgery decreased the overall elastic modulus by 7%, whereas CXL increased it by 20%. In enhancement, the corneal biomechanical integrity is less affected with both Re-SMILE and PRK enhancement. Corneal weakening through laser refractive surgery is small compared to the stiffening effect after CXL. [J Refract Surg. 2017;33(3):193-198.].


Lifestyle advice in preventing and treating type 2 diabetes.
Dietary advice from health professionals can play a significant part in preventing and managing type 2 diabetes. Overweight and obesity are strongly associated with this condition, and individually tailored advice on weight loss and maintaining an appropriate weight are useful, together with encouragement to take appropriate exercise. Current thinking about a healthy diet and lifestyle apply to people with type 2 diabetes, but those with this condition or who are at risk from it need to understand why diet and exercise are so important in their case. The article explores these issues, including specific aspects of diet such as carbohydrates and the glycaemic index.


Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator.
Berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo (5,6-a) quinolizinium] is an alkaloid present in plants of the Berberidaceae family and used in traditional Chinese and North American medicine. We have previously demonstrated that berberine causes mitochondrial depolarization and fragmentation, with simultaneous increase in oxidative stress. We also demonstrated that berberine causes an inhibition of mitochondrial respiration and a decrease on calcium loading capacity through induction of the mitochondrial permeability transition (MPT). The objective of the present work is to investigate a common target for both induction of the MPT and inhibition of respiration. The hypothesis is that berberine induces the MPT through interacting with the adenine nucleotide translocator (ANT). By measuring induction of the MPT through increased mitochondrial swelling, membrane depolarization and loss of calcium retention, we observed that the effects of berberine were not inhibited by bongkrekic acid although adenosine diphosphate (ADP)/oligomycin completely prevented the MPT. Also, we observed that berberine increased the depolarization effect of oleic acid on liver mitochondria. The initial depolarization observed when berberine is added to mitochondria was not affected by ANT inhibitors. Taken together, we propose that berberine acts on the ANT, altering the binding of the protein to bongkrekic acid but not to cyclosporin A or ADP. It is also clear that the membrane potential is required for berberine effects, most likely for allowing for its mitochondrial accumulation. Mitochondrial effects of berberine can be relevant not only for its proposed antitumor activity but also for the assessment of its organ toxicity, depending on factors such as tissue accumulation or delivery.


What makes sex offenders confess? An exploratory study.
This study examines correlates of offender confession in criminal sexual conduct cases involving children. The cases consist of all closed court files (N=318), spanning the last 10 years from a single jurisdiction. This jurisdiction has a community-wide protocol for handling child sexual abuse cases, a high rate of charging (69%), a high rate of confession (64%), and high rates of pleas to sex crimes (77%). To determine what factors were associated with suspect confession before adjudication, we examined characteristics of the suspect, the child, the abuse, and the system using bi-variate and multi-variate analysis. The following four variables are associated with suspect confession: (1) having the state police conducting the law enforcement part of the investigation, (2) more serious abuse, (3) younger age of the suspect, and (4) having a court appointed (as opposed to a retained) attorney.


Duane type I retraction syndrome associated with Wyburn-Mason syndrome.
Our aim is to report the co-existence of Duane's retraction syndrome and Wyburn-Mason syndrome, a rare condition characterized by arteriovenous malformations (AVMs) in the central nervous system and retina. An 11-year-old boy was referred for evaluation of strabismus present since birth. On examination his uncorrected visual acuity was 6/6 in each eye, with small angle left eye esotropia in the primary position, ipsilateral face turn, abduction deficit, lid fissure narrowing in adduction and widening in abduction; plus typical features of left-sided type I Duane syndrome were present. The left fundus demonstrated localized, well-compensated, markedly convoluted, dilated and tortuous retinal vessels and venous congenital retinal macrovessel, which traverse the macular region. The right fundus was unremarkable. In order to elucidate if this retinal vascular malformation is associated with similar lesions in the orbit, paranasal sinuses and/or brain, magnetic resonance imaging (MRI) was performed, followed by digital subtraction angiography of the brain vessels. Clinical features of retinal disease (typical retinal vascular malformation) and brain imaging studies have led to the diagnosis of Wyburn-Mason syndrome. Digital subtraction angiography of the brain revealed an AVM of 30 mm maximal diameter in the left occipital lobe. Intracranial AVM might have affected the normal vascular development during the second month of gestation, causing involutional changes of the sixth nerve and resulted in Duane's syndrome by "steal phenomenon." Retinal AVM may point to concomitant intracranial AVMs, thus warranting neurological assessment. Patients with AVM of the retina should be examined early with brain and orbital neuroimaging to rule out cerebral AVMs.


Association between an excessive body mass index and coronary heart disease risk factors in military personnel.
The purpose of this study was to document the extent of coronary heart disease (CHD) risk factors in military personnel (412 men, 50 women) classified as seriously overweight (body mass index [BMI] 27.0-29.9 kg/m2) or obese (BMI > or = 30 kg/m2) and to evaluate the utility of the BMI to discriminate among individuals with an adverse CHD risk profile. Mean body weight and BMI greatly exceeded Canadian norms, whereas mean heights were average. There were low but significant correlations between BMI and resting and submaximal exercise (stage A of the Canadian Aerobic Fitness Test) heart rates and blood pressures, while the correlation with predicted VO2max was negative. Except for blood glucose level (GLU) in men, there were no significant correlations between BMI and various biochemical indices. Compared to "overweight" men, the percentage of "obese" men with abnormal values for risk factors were higher, particularly for an adverse exercise blood pressure response and low predicted VO2max. In summary, the correlations between BMI and the various CHD risk factors, except for GLU and the exercise parameters, were minimal or moderate at best. It was concluded that in overweight and obese individuals, BMI does not appear to be a particularly sensitive indicator of body fat and risk factors.


Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer.
Niclosamide, an anthelmintic drug approved by the US Food and Drug Administration against cestodes, is used to treat tapeworm infection. In this study, we show that niclosamide can potentially inhibit signal transducer and activator of transcription 3 (STAT3) in colon cancer cell lines. Combined inhibition of epidermal growth factor receptor and STAT3 by erlotinib and niclosamide synergistically induces apoptosis and antiproliferation in colon cancer cell lines. Our findings suggest that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer.


[Efficacy of topical 2% cyclosporine A as a steroid-sparing agent in steroid-dependent vernal keratoconjunctivitis].
Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival and corneal inflammation that often requires topical steroids. Steroid dependency is not rare and can lead to unacceptable complications. The aim of this study was to analyze the efficacy of 2% cyclosporine eye drops (CsA) as a steroid-sparing agent in steroid-dependent VKC. In this noncomparative interventional case series, 18 steroid-dependent VKC patients (17 males, 1 female; mean age, 13 years old) received 2% CsA qid. Topical steroids were associated at decreasing dosage for 1 week and stopped if possible. Efficacy was graded at 1 and 3 months on symptoms, signs and steroid use. Local and systemic tolerability (cyclosporinemia, creatininemia) was also assessed. After 1 month, inflammation was controlled without steroids in 11 cases (61%). Low-dose steroids were still necessary to control the disease in four cases (22%). In three cases (17%), the disease was not controlled despite high-dose steroids. At 3 months, results were similar. All patients whose inflammation was partially controlled or not controlled by CsA had active extraocular atopic diseases. Local and systemic tolerability was excellent. Topical 2% cyclosporine is inconstantly effective in steroid-dependent VKC. However, this treatment allows for a partial or total reduction of steroids in most cases.


Bridging with Tirofiban during Oral Antiplatelet Interruption: A Single-Center Case Series Analysis Including Patients on Hemodialysis.
Patients requiring an interruption in dual-antiplatelet therapy (DAPT) within 6 months of cardiac stenting are at risk for thrombotic events. Bridging with short-acting intravenous antiplatelet agents has been proposed to minimize the risk of thrombotic and hemorrhagic complications. This retrospective analysis of a tirofiban bridging strategy did not use an initial bolus loading dose. Tirofiban infusions were initiated 24-48 hours after the last oral antiplatelet dose at a rate of 0.1 μg/kg/min (or 0.05 μg/kg/min if renal dysfunction) and continued until 4-8 hours before surgery or until DAPT could be resumed. Coprimary end points were occurrence of major adverse cardiac events (MACE) and bleeding. Twenty patients requiring DAPT interruption within 6 months of cardiac stenting for either a surgical procedure or who were unable to take any medications by mouth were included. The median time from stent implantation to DAPT interruption was 33 days (range 3-146 days). Two patients experienced a MACE during their hospital stay. No major bleeding events occurred; minor bleeding occurred in four patients during tirofiban therapy. Five patients in this analysis had end-stage renal disease requiring hemodialysis. Of these patients, no MACE or major bleeding events occurred. This analysis observed that a tirofiban bridging strategy without an initial bolus loading dose has comparable efficacy and safety as previously published reports. A tirofiban infusion without bolus dosing may be a safe option for antiplatelet bridging in patients with a recent cardiac stent implant to prevent stent thrombosis.


Growth hormone and somatostatin gene expression in adult and aging rats as measured by quantitative in situ hybridization.
We have investigated the variations in growth hormone (GH) and somatostatin (SOM) mRNAs in adult, middle-aged and aging rats of both sexes using quantitative in situ hybridization. cDNA probes complementary to GH mRNA and SOM mRNA were used on fixed pituitary and hypothalamic sections, respectively. A clear sexual dimorphism in GH gene expression was observed in all age groups examined, mRNA levels always being higher in males than in females. In male rats, GH mRNA levels reached a maximum at 7 months of age and then dramatically decreased in middle-aged and aging animals. In female animals, the highest expression of GH was observed at 9 months of age followed by a gradual and constant decline during the aging period. SOM mRNA levels in the periventricular nucleus of the hypothalamus also showed a sexual dimorphism in adult rats, being higher in males than females. A gradual decline in SOM mRNA was observed in middle-aged and aging rats of both sexes. These results suggest that middle age and aging are critical periods for the control of GH and SOM gene expression and that the decrease in GH mRNA levels observed during aging is probably not a consequence of an increase of SOM activity.


Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway.
Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell-extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein-tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG-induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG-induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis.


[Inflammatory bowel disease and pulmonary embolism: Because of 3 cases].
Thromboembolic complications are an important cause of morbidity and mortality in inflammatory bowel diseases (IBD). Thromboembolic events are observed more frequently during acute flare of the disease, especially patients received steroid therapy. Increase in awareness and especially anticoagulation prophylaxis in these patients are extremely important. In this article, three cases with diagnosed pulmonary thromboembolism (PE) were presented accompanied by the current literature.


Molecular mechanisms for cooperative folding of proteins.
The folding of single-domain globular proteins exhibits the character of first-order or two-state thermodynamics. The origin of such high cooperativity in relatively small polymer systems is still not well understood. Recently, the statistical mechanics of protein folding has been studied extensively with simple protein models such as short cubic-lattice chains with contact-based interactions. While many valuable insights about protein folding were gained with such models, some concerns have also arisen, viz. that they lack the character of protein backbones whose interactions would limit the folding patterns of proteins. Here, a comparative study of the conventional cubic-lattice chain model and a fine-grained more realistic lattice protein model with both backbone and side-chain interactions is carried out. It is found that, even though both types of models exhibit a cooperative two-state folding transition to the native structure with optimized force fields, the character and origin of cooperativity of the two models are different. In the simple contact-based model, the free-energy barrier occurs at the low end of the energy scale, and the cooperativity arises from a concerted formation of native contacts among many residues in a compact state. In the other more complicated model, the free-energy barrier occurs in the intermediate energy region, and the folding cooperativity arises from collective orientational arrangements of locally structured units in semi-open conformational states. On the basis of these results, two limiting molecular mechanisms for protein folding emerge, which can be used for analyzing the folding process of real proteins.


Nonlinearity of a metamaterial arising from diode insertions into resonant conductive elements.
We consider a possibility to create a metamaterial with nonlinear magnetic response in the microwave frequency range. Such a metamaterial is a regular periodic three-dimensional-array of resonant conductive elements with diodes as nonlinear insertions. We calculate the arising quadratic nonlinear susceptibility and show how it is controlled by the properties and arrangement of the structure elements as well as by the type and characteristics of the diode. We discuss the requirements for the diode necessary to optimize the nonlinear response of the proposed metamaterial.


Additional Conditions Amenable to Observation Care.
ED observation units (EDOUs) are designed for patients who require diagnostics or therapeutics beyond the initial ED visit to determine the need for hospital admission. Best evidence is that this care be delivered via ordersets or protocols. Occasionally, patients present with conditions that are amenable to EDOU care but fall outside the commonly used protocols. This article details a few of these conditions: abnormal uterine bleeding, allergic reaction, alcohol intoxication, acetaminophen overdose and sickle cell vaso-occlusive crisis. It is not meant to be exhaustive as patient care needs can vary hospital to hospital.