A prospective observational study of the utility of early diagnostic laparoscopy for right lower abdominal pain: a safe and effective diagnostic and therapeutic tool.
Diagnostic laparoscopy is commonly performed for diagnosis of right lower abdominal pain and its use is increasing in the emergency setting. Some studies have reported that diagnostic laparoscopy and laparoscopic appendicectomy have advantages over conventional surgery. Many emergency surgeons now perform diagnostic laparoscopy for both clinically diagnosed appendicitis and when the diagnosis is in doubt. The aim of the present study was to assess whether the use of diagnostic laparoscopy is justified and safe for those admitted with right lower abdominal pain. Data were collected prospectively on consecutive patients attending the acute surgical receiving unit with right iliac fossa pain or a suspected diagnosis of acute appendicitis. A total of 284 patients underwent diagnostic laparoscopy. Of them 233 (82%) had a positive finding at laparoscopy, 207 (88%) underwent appendicectomy, the majority of which were carried out laparoscopically. Surgical trainees performed the majority of operations and this did not have a negative impact on operative findings (p 0.856), operation performed (0.642), or operative duration (0.831). No intra-operative complications were sustained. Ultrasound examination was carried out in 49 patients, while CT was carried out in 24. The results of the present study highlight the utility of early diagnostic laparoscopy as both a diagnostic and therapeutic tool in the acute setting.


Acquisition and maintenance of autoshaped key pecking as a function of food stimulus and key stimulus similarity.
The results of a number of recent studies suggest that acquisitions of autoshaped key pecking in pigeons is affected by the similarity of the grain-hopper stimulus and response-key stimulus. In Experiment 1 this hypothesis was tested by training independent groups of pigeons to key peck under six different hopper-stimulus and key-stimulus similarity conditions, and three procedures containing either immediate reinforcement, variable delay of reinforcement, or omission of reinforcement for key pecking. Number of trials to acquisition was found to be related to the similarity variable. Maintained responding was affected by the response-reinforcer contingency. This effect was found both within and between subjects. Under two of the contingencies (automaintenance and omission), maintained responding continued to be affected by the similarity of the hopper stimulus and key stimulus. In Experiment 2 pigeons were given omission training with a hopper light on or off. Both acquisition and maintenance of key pecking were facilitated by the presence of the hopper light. The present findings suggest that much of the responding reported in various automatic shaping and training procedures may reflect the effects of key stimulus/food stimulus similarity.


Ultra-morphological study of the interaction of dental adhesives with carbamide peroxide-bleached enamel.
To evaluate the effects of a carbamide peroxide bleaching agent on interfaces formed by two one-bottle dental adhesives to etched enamel. The null hypotheses tested in this study were that vital bleaching with a commercial 10% carbamide peroxide gel would not (1) increase the concentration of oxygen in the superficial layer of enamel or (2) induce ultra-morphological changes in resin-enamel interfaces. Five extracted human incisors were treated with 10% carbamide peroxide (Opalescence) for 4 h/day for 1 week and were compared with non-bleached teeth for oxygen, calcium, and phosphorus relative concentration using EDS. Mean elemental concentrations were analyzed using a t-test (bleached vs. unbleached enamel), one-way ANOVA (for surface location and also for depth) and three-way ANOVA (with bleaching treatment, surface location, and depth as the main factors). For TEM, fifteen extracted human molars were sectioned to obtain two crown halves. After roughening the occlusal surface, one half was bleached with Opalescence while the other half was stored in artificial saliva for 1 week. Enamel was etched for 15 s with a 35% phosphoric acid and bonded with one of three adhesives (Prime & Bond 2.1, Syntac Single-Component, or Scotchbond Multi-Purpose Adhesive-control) and a composite resin (Protect Liner F). Small enamel/resin sticks with a cross-section of 1.0 mm x 1.0 mm were removed and the specimens were processed for TEM observation. Vital bleaching with 10% carbamide peroxide caused no significant changes in relative oxygen concentration of enamel. For calcium and phosphorus, bleaching resulted in significant decreased relative concentrations. Bleaching also resulted in morphological alterations in the most superficial enamel crystallites. Some altered crystallites exhibited electron-lucent cores and reduced thickness of material around the core.


Gas film retention and underwater photosynthesis during field submergence of four contrasting rice genotypes.
Floods can completely submerge some rice (Oryza sativa L.) fields. Leaves of rice have gas films that aid O2 and CO2 exchange under water. The present study explored the relationship between gas film persistence and underwater net photosynthesis (PN) as influenced by genotype and submergence duration. Four contrasting genotypes (FR13A, IR42, Swarna, and Swarna-Sub1) were submerged for 13 days in the field and leaf gas films, chlorophyll, and the capacity for underwater PN at near ambient and high CO2 were assessed with time of submergence. At high CO2 during the PN assay, all genotypes initially showed high rates of underwater PN, and this rate was not affected by time of submergence in FR13A. This superior photosynthetic performance of FR13A was not evident in Swarna-Sub1 (carrying the SUB1 QTL) and the declines in underwater PN in both Swarna-Sub1 and Swarna were equal to that in IR42. At near ambient CO2 concentration, underwater PN declined in all four genotypes and this corresponded with loss of leaf gas films with time of submergence. FR13A retained leaf gas films moderately longer than the other genotypes, but gas film retention was not linked to SUB1. Diverse rice germplasm should be screened for gas film persistence during submergence, as this trait could potentially increase carbohydrate status and internal aeration owing to increased underwater PN, which contributes to submergence tolerance in rice.


Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target.
Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. Ovaries and pelvic peritoneum are the most common locations for endometrial ectopic tissue, followed by deep infiltrating EM sites. The cyclic and recurrent bleeding, the progressive fibrosis and the peritoneal adhesions of ectopic endometrial glands, may cause different symptoms depending on the origin involved. EM is a frequent clinical condition affecting around 10% of women of mainly reproductive age, as well as in post-menopausal women and adolescents, especially with uterine anomalies. The risk of developing EM depends on a complex interaction between genetic, immunological, hormonal, and environmental factors. It is largely considered to arise due to a dysfunction of immunological surveillance. In fact, women with EM exhibit altered functions of peritoneal macrophages, lymphocytes and natural killer cells, as well as levels of inflammatory mediators and growth factors in the peritoneal fluid. In EM patients, peritoneal macrophages are preponderant and highly active compared to healthy women. Peritoneal macrophages are able to regulate the events that determine the production of cytokines, prostaglandins, growth factors and complement components. Several studies have shown alteration in the regulation of the complement activation, leading to chronic inflammation characteristic of EM. Aberrant regulation/activation of the complement system has been observed in the peritoneal cavity of women affected by EM. Thus, complement inhibition may represent a new approach for the treatment of EM, given that a number of complement inhibitors are under pre-clinical and clinical development. Such an intervention may provide a broader therapeutic control of complement-mediated inflammatory damage in EM patients. This review will focus on our current understanding of the role of complement activation in EM and possible modalities available for complement-based therapy.


Gaussian Process Panel Modeling-Machine Learning Inspired Analysis of Longitudinal Panel Data.
In this article, we extend the Bayesian nonparametric regression method Gaussian Process Regression to the analysis of longitudinal panel data. We call this new approach Gaussian Process Panel Modeling (GPPM). GPPM provides great flexibility because of the large number of models it can represent. It allows classical statistical inference as well as machine learning inspired predictive modeling. GPPM offers frequentist and Bayesian inference without the need to resort to Markov chain Monte Carlo-based approximations, which makes the approach exact and fast. GPPMs are defined using the kernel-language, which can express many traditional modeling approaches for longitudinal data, such as linear structural equation models, multilevel models, or state-space models but also various commonly used machine learning approaches. As a result, GPPM is uniquely able to represent hybrid models combining traditional parametric longitudinal models and nonparametric machine learning models. In the present paper, we introduce GPPM and illustrate its utility through theoretical arguments as well as simulated and empirical data.


The influence of personal networks on the use and abuse of alcohol and drugs.
Party networks of young people are very important for socialization, but can also influence their involvement in risk behaviours or they can be protective. The influence of nightlife network of friends in using alcohol/ drugs is investigated through a survey. We explore the individual-centred networks (7.360 friends) of 1.363 recreational nightlife users in 9 European cities in 2006, through 22 friend characteristics. Statistical analysis utilised factorial analysis with varimax rotation and analysis of variance. The 69% of the sample had been drunk during the last month and more than half of them had used illicit drugs. Most of the respondents use to have a stable group of friends with whom to go out. Networks main characteristics were being more or less deviant and/or prosocial. Having not network or a less prosocial network is related to be low consumers. Having a non deviant, but prosocial network is related to being a person who gets drunk without using illegal drugs. Users of illegal drugs have a deviant and prosocial network. Finally ex users have less deviant networks, but at the same time a helper and prosocial network. Males drug use patterns appear to be less affected by the characteristics of their networks. Some preventive consequences coming from these results are already known as the importance of having less deviant friends. But some other issues are less known: to enhance certain prosocial skills may have counter preventive effects among recreational users and to influence the network for preventative purposes may be more effective among females.


Characterization of interactions among the Cef1p-Prp19p-associated splicing complex.
Schizosaccharomyces pombe (Sp) Cdc5p and its Saccharomyces cerevisiae (Sc) ortholog, Cef1p, are essential components of the spliceosome. In S. cerevisiae, a subcomplex of the spliceosome that includes Cef1p can be isolated on its own; this has been termed the nineteen complex (Ntc) because it contains Prp19p. Components of the Ntc include Cef1p, Snt309p, Syf2p/Ntc31p, Ntc30p/lsy1p, Ntc20p and at least six unidentified proteins. We recently identified approximately 30 proteins that copurified with Cdc5p and Cef1p. Previously unidentified S. pombe proteins in this purification were called Cwfs for complexed with five and novel S. cerevisiae proteins were called Cwcs for complexed with Cef1p. Using these proteomics data coupled with available information regarding Ntc composition, we have investigated protein identities and interactions among Ntc components. Our data indicate that Cwc2p, Prp46p, Clf1p, and Syf1p most likely represent Ntc40p, Ntc50p, Ntc77p, and Ntc90p, respectively. We show that Sc Cwc2p interacts with Prp19p and is involved in pre-mRNA splicing. Sp cwf2+, the homolog of Sc CWC2, is allelic with the previously identified Sp prp3+. We present evidence that Sp Cwf7p, an essential protein with obvious homologs in many eukaryotes but not S. cerevisiae, is a functional counterpart of Sc Snt309p and binds Sp Cwf8p (a homolog of Sc Prp19p). Further, our data indicate that a mutation in the U-box of Prp19p disrupts these numerous protein interactions causing Cef1p degradation and Ntc instability.


[CT fluoroscopy].
Percutaneous biopsy of pulmonary nodules requires precise needle placement, with the goal of attaining a secure position of the needle for therapeutic or diagnostic purposes as quickly as possible and with minimal tissue damage along the access route. The requirements from the image guidance system during the intervention are, in addition to universal applicability, a quick reaction time and a user-friendly interface. CT fluoroscopy fulfils these requirements, although radiation protection for the patient and radiologist becomes an important issue.


[Concordance between Procam and Framingham cardiovascular risk scores among men receiving HIV treatment at a National Hospital in Lima, Peru 2013].
The aim of the study is to determine the concordance between the PROCAM (Prospective Cardiovascular Münster) and Framingham scales in patients receiving highly active antiretroviral therapy (HAART). A cross sectional study was conducted in HIV-positive male population who use HAART in a national reference hospital located in Lima, Peru. To evaluate the concordance between the two scales the graphic method of Bland and Altman was used, for the evaluation of the correlation we used the Pearson coefficient and to measure the agreement we use the kappa coefficient. 111 patients were enrolled, with an average age of 47.0 years. The distribution of patients according to the risk was low, moderate and high, 81.2%, 13.6% and 5.4% respectively for PROCAM and 71.2%, 25.2% and 3.6% for Framingham. According to the graphic method of Bland and Altman, the concordance was adequate in low values and was lost as the risk score increased. Pearson's test found a strong correlation (r=0.87 and p<0.05) and the kappa coefficient was 0.56 (p<0,001). The agreement we found at low risk decreases as the risk increases. Strong correlation was found between the two scales. We recommend further studies in order to know which scale of cardiovascular risk is the most optimal scale for clinical practice among HIV population who receive HAART.


Intramammary application of non-methylated-CpG oligodeoxynucleotides (CpG) inhibits both local and systemic mammary carcinogenesis in female BALB/c Her-2/neu transgenic mice.
CpG are powerful drugs activating the innate immune system. In this study, the ability of their intramammary administration in impeding the devastating progression of carcinogenesis in all the mammary glands of female BALB/c mice transgenic for the rat neu transforming oncogene was assessed. Starting when in situ carcinomas were scattered over all their mammary glands (week 10), mice received CpG injections in the stroma of the fourth left gland. Local neoplastic progression was inhibited by six monthly administrations. CpG not only delayed the onset of carcinomas in the injected gland, but also hampered their progression. Extended latency was observed for tumors in glands both close to and far from the injection site. When the experiment ended (week 45), no tumors were palpable in 67% of the injected glands and a markedly impaired tumor growth was evident in the others. An impressive local infiltrate of CD11b(+) cells with the morphologic features of macrophages, plasma cells, B220(+) B cells, and CD4(+) and CD8(+) T cells was quickly recruited to the CpG-treated glands. High quantities of IFN-gamma producing cells were only present in the ipsilateral axillary draining lymph nodes of the treated glands. Enhanced natural killer (NK) lytic activity was also detected in the spleens. Inhibition of progression was weaker when only four injections were given, and abolished by in vivo depletion of NK cells. CpG monotherapy is thus effective in an aggressive model of autochthonous cancer. The results strongly support the administration of CpG as a local monotherapy of multiple invasive microscopic lesions.


The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa.
Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites. To our knowledge, we describe the first case in which a newborn with EB, Dowling-Meara variant, was treated with bilayered tissue-engineered skin. The areas treated with the tissue-engineered skin healed faster than the areas treated with conventional therapy. Most of the areas treated with tissue-engineered skin have remained healed, without developing new blisters. These areas appear to be more resistant to trauma. Our early success with tissue-engineered skin in this patient may have a significant impact on the future treatment of neonates with EB simplex. Future studies are needed to determine if the beneficial effects of tissue-engineered skin are reproducible in other neonates with EB simplex and in patients of all ages with different subtypes of EB.


Heavy metals and organochlorinated compounds in the European eel (Anguilla anguilla) from the Adour estuary and associated wetlands (France).
Heavy metals and organic pollutants were investigated in the Adour estuary (South West France) and associated wetlands using the European eel (Anguilla anguilla) as a bioindicator. Heavy metals (Cu, Cd, Zn, Pb, and Ag) were measured in soft tissue of yellow eels. Mercury (total Hg and MeHg) and organochlorinated compounds (7 PCBs, 11 OCPs) were analysed in muscle. Concentrations in muscle were in agreement with moderately contaminated environments in Europe and were below the norms fixed for eel consumption for heavy metals and OCPs. Analyses of liver showed a higher pressure of Ag and Zn in the downstream estuary than in the freshwater sites whereas Cd was lower in the estuary probably because of the salinity influence. According to quality classes 100% of eels from freshwater sites indicated clean or slightly polluted environments. However, total mercury concentrations were close to the thresholds fixed by the European Community in the downstream estuary, whereas the sum of PCBs was found to be greatly above the fixed value. 100% of the individuals from the estuary were classified in quality classes corresponding to polluted or highly polluted sites. These first results highlight the need of further investigations focused on mercury and PCBs in this area taking the seasonal temperature influence into account for a better understanding of the pollution distribution and the possible threat on the eel population from the Adour basin.


[In Process Citation].
To compare the life quality between the initial and recurrent patients with osteoporotic vertebral compression fractures (OVCFs) after conservative treatment, and to explore the influential factors on life quality in the recurrent fracture patients. A total of 30 patients with recurrent fractures after the OVCFs were retrospectively observed. At the same time, 30 initial OVCFs patients with similar basic conditions to the patients in the recurrent fractures group were served as a control group. The data of the SF-36 Concise Health Status Questionnaire in the 2 groups were compared. The eight dimensions of the SF-36 Concise Health Status Questionnaire in the recurrent fracture group were worse than those in the control group (all P<0.01). The life quality for patients with the recurrent fracture is significantly poorer than that in the control group. The patients with recurrent fracture of the OVCFs may further affect their psychological expectation, emotion and social activities.


The italian network of primary immunodeficiencies.
Primary immunodeficiencies are rare diseases, characterized by an increased susceptibility to infections. Early diagnosis and appropriate treatment are critical for reducing morbidity and mortality. Given the rarity of these diseases, the awareness of these disorders by physicians is often insufficient, leading to delayed diagnosis and inappropriate treatment which are the major causes of severe long term complications. In an attempt to address and resolve these problems an Italian Network on primary immunodeficiencies has been established with the aim to increase the awareness of these disorders among physicians and to provide the best clinical assistance to all patients on the national territory.


Catalytic roles of yeast GSK3beta/shaggy homolog Rim11p in meiotic activation.
In Saccharomyces cerevisiae, many meiotic genes are activated by a heteromeric transcription factor composed of Ime1p and Ume6p. Ime1p-Ume6p complex formation depends upon the protein kinase Rim11p, which interacts with and phosphorylates both Ime1p and Ume6p in vitro. Rim11p may promote complex formation through its phosphorylation of Ime1p and Ume6p or simply through its interaction with both proteins. Here, we characterize mutant Ime1p derivatives that interact with Rim11p but are not phosphorylated in vitro. These mutant proteins are also defective in interaction with Ume6p. These results argue that Ime1p must be phosphorylated to interact with Ume6p. Our genetic observations suggest that Ime1p tyrosine residues are among the Rim11p phosphoacceptors, and we find that Ime1p reacts with an anti-phosphotyrosine antibody. Ime1p and Rim11p have been thought to act only through Ume6p, but we find that Ime1p and Rim11p promote meiosis at a very low level in the absence of Ume6p. A nonphosphorylatable mutant Ime1p derivative promotes sporulation through this Ume6p-independent pathway, as does a mutant Rim11p derivative that fails to interact with Ime1p. Therefore, Ime1p and Rim11p have two genetically separable functions in the sporulation program. However, catalytic activity of Rim11p is required for sporulation in the presence or absence of Ume6p.


SiNC: Saliency-injected neural codes for representation and efficient retrieval of medical radiographs.
Medical image collections contain a wealth of information which can assist radiologists and medical experts in diagnosis and disease detection for making well-informed decisions. However, this objective can only be realized if efficient access is provided to semantically relevant cases from the ever-growing medical image repositories. In this paper, we present an efficient method for representing medical images by incorporating visual saliency and deep features obtained from a fine-tuned convolutional neural network (CNN) pre-trained on natural images. Saliency detector is employed to automatically identify regions of interest like tumors, fractures, and calcified spots in images prior to feature extraction. Neuronal activation features termed as neural codes from different CNN layers are comprehensively studied to identify most appropriate features for representing radiographs. This study revealed that neural codes from the last fully connected layer of the fine-tuned CNN are found to be the most suitable for representing medical images. The neural codes extracted from the entire image and salient part of the image are fused to obtain the saliency-injected neural codes (SiNC) descriptor which is used for indexing and retrieval. Finally, locality sensitive hashing techniques are applied on the SiNC descriptor to acquire short binary codes for allowing efficient retrieval in large scale image collections. Comprehensive experimental evaluations on the radiology images dataset reveal that the proposed framework achieves high retrieval accuracy and efficiency for scalable image retrieval applications and compares favorably with existing approaches.


A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres.
Our goal was to limit liver toxicity and to obtain good efficacy by developing a dosimetric treatment planning strategy. While several dosimetric evaluations are reported in literature, the main problem of the safety of the treatment is rarely addressed. Our work is the first proposal of a treatment planning method for glass spheres, including both liver toxicity and efficacy issues. Fifty-two patients (series 1) had been treated for intermediated/advanced hepatocellular carcinoma (HCC) with glass spheres, according to the Therasphere® prescription of 120 Gy averaged on the injected lobe. They were retrospectively evaluated with voxel dosimetry, adopting the local deposition hypothesis. Regions of interest on tumor and non tumor parenchyma were drawn to determine the parenchyma absorbed dose, averaged also on non irradiated voxels, excluding tumor voxels. The relationship between the mean non tumoral parenchyma absorbed dose D and observed liver decompensation was analyzed. Basal Child-Pugh strongly affected the toxicity incidence, which was 22% for A5, 57% for A6, 89% for B7 patients. Restricting the analysis to our numerically richest class (basal Child-Pugh A5 patients), D median values were significantly different between toxic (median 90 Gy) and non toxic treatments (median 58 Gy) at a Mann-Withney test, (P=0.033). Using D as a marker for toxicity, the separation of the two populations in terms of area under ROC curve was 0.75, with 95% C.I. of [0.55-0.95]. The experimental Normal Tissue Complication Probability (NTCP) curve as a function of D resulted in the following values: 0%, 14%, 40%, 67% for D interval of [0-35] Gy, [35-70] Gy, [70-105] Gy, [105-140] Gy. A limit of about 70 Gy for the mean absorbed dose to parenchyma was assumed for A5 patients, corresponding to a 14% risk of liver decompensation. This result is applicable only to our administration conditions: glass spheres after a decay interval of 3.75 days. Different safety limit (40 Gy) are published for resin spheres, characterized by higher number of particle per GBq (more uniform irradiation, bigger biological effect for the same absorbed dose). As result of this study we suggest a constraint of about 70 Gy mean absorbed dose to liver non tumoral parenchyma, corresponding to about 15% probability of radioinduced liver decompensation while still aiming at achieving an absorbed of several hundreds of Gy to lesions.


Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in children.
The pharmacokinetics of cefetamet were determined after intravenous (i.v.) administration of cefetamet and oral administration of cefetamet pivoxil syrup to patients between the ages of 3 and 12 years. The patients were hospitalized for reconstructive urological surgery; to prevent infection, prophylactic i.v. cefetamet was administered on the day of surgery and oral cefetamet pivoxil was administered 2 days later. After i.v. administration, the mean (+/- standard deviation) half-life of cefetamet was 1.97 +/- 0.60 h (n = 18), which was different from the 2.46 +/- 0.33 h reported for nine adults (22 to 68 years old) in a previous study. The average values for the mean residence times were 2.35 +/- 0.94 and 2.83 +/- 0.34 h and the average values for the fraction of the dose eliminated unchanged in the urine were 79.9% +/- 8.99% and 80% +/- 11% in children and adults, respectively. Plots of mean systemic clearance and steady-state volume of distribution versus body weight for the children and comparative adults were linear on log-log coordinates, and the slopes of the plots were 0.661 and 0.880, respectively. These slope values suggested that mean systemic clearance values per unit of body surface area were similar in children and adults and that maintenance doses for children should be the adult maintenance dose multiplied by the child's surface area divided by 1.73 m2. The mean (+/- standard deviation) oral bioavailabilities of cefetamet pivoxil were 49.3% +/- 15.7% in 3- to 7-year-old children who received a 500-mg dose and 37.9% +/- 10.0% in 8- to 12-year-old children who received a 1,000-mg dose. These values were not different from that observed in the adult group after two 500-mg tablets. Likewise, the peak concentration of cefetamet in plasma and its time of occurrence in children were in line with the values which have been observed for adults.


Diverse gut pathogens exploit the host engulfment pathway via a conserved mechanism.
Macrophages clear infections by engulfing and digesting pathogens within phagolysosomes. Pathogens escape this fate by engaging in a molecular arms race; they use WxxxE motif-containing "effector" proteins to subvert the host cells they invade and seek refuge within protective vacuoles. Here, we define the host component of the molecular arms race as an evolutionarily conserved polar "hot spot" on the PH domain of ELMO1 (Engulfment and Cell Motility protein 1), which is targeted by diverse WxxxE effectors. Using homology modeling and site-directed mutagenesis, we show that a lysine triad within the "patch" directly binds all WxxxE effectors tested: SifA (Salmonella), IpgB1 and IpgB2 (Shigella), and Map (enteropathogenic Escherichia coli). Using an integrated SifA-host protein-protein interaction network, in silico network perturbation, and functional studies, we show that the major consequences of preventing SifA-ELMO1 interaction are reduced Rac1 activity and microbial invasion. That multiple effectors of diverse structure, function, and sequence bind the same hot spot on ELMO1 suggests that the WxxxE effector(s)-ELMO1 interface is a convergence point of intrusion detection and/or host vulnerability. We conclude that the interface may represent the fault line in coevolved molecular adaptations between pathogens and the host, and its disruption may serve as a therapeutic strategy.


Does increased free flap size in the head and neck region impact clinical outcome?
There are few studies analyzing the long-term clinical effects related to increasing the size of head and neck free tissue reconstructions. The purpose of this study was to compare long-term clinical outcomes of patients undergoing very large area (≥200 cm(2)) and large area (100 to 199 cm(2)) free tissue reconstructions of head and neck defects. Institutional review board approval was obtained before conducting this retrospective cohort study at the authors' university-based tertiary care hospitals. The authors analyzed the charts of consecutive patients with free flaps of at least 100 cm(2) treated from July 2000 to December 2011. Very large area flaps were arbitrarily defined as larger than 200 cm(2). Intraoperative variables, flap success rates, overall survival, and total hospital and intensive care unit (ICU) stays for the 2 groups were analyzed. Fisher exact tests or χ(2) tests were used for categorical variables and Student t tests were used for continuous variables. Log-rank tests were conducted to investigate whether overall survival was significantly different between the 2 groups. Statistical significance was defined as a P value less than .05. The charts of 121 consecutive patients were analyzed. Thirty-eight patients (31%) had very large area flaps (277.1 ± 79.4 cm(2); range, 200 to 576 cm(2)) and 83 patients (69%) had large area flaps (140.1 ± 25.5 cm(2)). There was no difference between flap groups in presenting T4 stage disease (P = .448). Ninety-eight percent of the very large area flaps and 93% of the large area flaps survived. Total hospital stays for the very large area and large area flap groups were 12.8 ± 8.2 and 12.3 ± 8.3 days, respectively (P = not significant). In contrast, ICU stays were increased for the very large area flap group at 7.1 ± 7.5 versus 4.0 ± 4.0 days for the large area flap group (P = .022). The overall median patient survival for the very large area flap group was 7.6 months (95% confidence interval, 5.7-10.0) and that for the large area flap group was 8.4 months (95% confidence interval, 5.4-12.9; P = .376). Performing very large area flaps for head and neck reconstruction did not negatively affect clinical outcome. Comparable success rates, total hospital stays, and overall survival can be safely achieved in this difficult patient population. More studies need to be conducted on resource usage.


A matrix isolation ESR investigation of the MgCH radical.
The MgCH radical and its magnesium-25, carbon-13, and deuterated isotopologs have been isolated in low temperature neon matrices and examined by the matrix isolation electron spin resonance technique for the first time. The radicals were formed through the reactions of laser ablated natural abundance magnesium metal and magnesium-25 enriched magnesium metal with carbon-13 and deuterated isotopologs of acetone. The MgCH radical was shown to have a X4Σ- ground electronic state, and the magnetic parameters determined for this state were g⊥ = 2.001 81(45), g∥ = 2.0018(10), D = 4970(5) MHz, A⊥(13C) = 115(6) MHz, A∥(13C) = 65(15) MHz, A⊥(H) = 34(6) MHz, A∥(H) = 5(10) MHz, A⊥(D) = 5(3) MHz, A⊥(25Mg) = 82(5) MHz, and A∥(25Mg) = 85(10). Comparisons are made between the electronic structure of this radical and the MgCH3 and MgN radicals. Theoretical hyperfine parameters were also evaluated for the MgCH radical, and a potential energy surface for the low-lying electronic states was constructed using complete active space multiconfigurational self-consistent field theory. The leading configuration (96.6%) for the X4Σ- ground electronic state was shown to be 1σ22σ23σ21π44σ25σ26σ27σ12π12π1 with an Mg-C bond length of 2.041 Å for a fixed C-H bond length of 1.090 Å. The Mg-C bond dissociation energy (De) was 48.26 kcal/mol. The optimized geometry from a density functional theory calculation using the B3LYP functional gave a Mg-C bond length of 2.061 Å and a C-H bond length of 1.090 Å.


Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms.
This study assessed the diagnostic approaches of Helicobacter pylori (IP)-associated iron deficiency (ID) and anemia (IDA) in children with dyspeptic symptoms and evaluated the effect of simultaneous anti-H. pylori (anti-HIP) therapy and oral iron in comparison with each of anti? HP therapy and oral iron therapy alone, on iron status as assessed by serum soluble transferrin receptor (sTfR) level. Two hundreds children with dyspeptic symptoms were subjected to clinical evaluation, stool examination, CBC, biochemical assays for serum iron parameters and measurements of serum IgG antibodies to HP and serum sTfR level by ELISA. Sixty children were found to have HP. associated ID or IDA and were randomly divided into 3 groups (20 children each). GA received 2-week anti-HP therapy plus 90-day oral iron, and GB received 2-week anti-HP therapy alone whereas group C received 90-day oral iron alone. Re-evaluation of the 3 groups was performed after 3 months of treatment initiation by repeat CBC and serum sTfR level. Children (45%) were HP-seropositive. The mean values of serum sTfR were significantly higher in HP-positive group and in HP-positive children with IDA than in HP-negative group and in HP-negative children with IDA although no significant differences were noted in hematologic variables and iron parameters between the corresponding groups and children. As regard treatment groups, there were significant improvements in the mean values of indices of IDA status (HIb, MCH, MCV, sTfR) and ID status (sTtRi) at 3 months of treatment initiation compared with their baseline values after. anti-HP triple therapy either with oral iron or without oral iron whereas the control children who were treated with oral iron alone showed insignificant changes despite oral iron administration. The improvements in these parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone, where compared with those who did not receive anti-HP therapy. Their magnitudes were significantly higher among children receiving anti-HP therapy combined with oral iron when compared with that receiving anti-HP therapy alone.


Three-Dimensional Bio-Printed Cardiac Patch for Sustained Delivery of Extracellular Vesicles from the Interface.
Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect on residing cells or EVs. The resulting 3D bio-printed CP was examined for its mechanical stiffness, showing an elastic modulus between 4-5 kPa at day 1 post-printing, suitable for transplantation. Affinity binding of EVs to alginate sulfate (AlgS) was validated, exhibiting dissociation constant values similar to those of EVs with heparin. The incorporation of AlgS-EVs complexes within the shell bioink sustained EV release from the CP, with 88% cumulative release compared with 92% without AlgS by day 4. AlgS also prolonged the release profile by an additional 2 days, lasting 11 days overall. This CP design comprises great potential at promoting more efficient patch assimilation with the host.


Stimulus parameters governing confusion effects in forward masking.
In forward masking, performance may be affected by confusion, that is, by the difficulty of discriminating a suprathreshold signal from the preceding masker. This study investigated confusion effects for forward maskers composed of repeated bursts of a 100-Hz sinusoid followed by sinusoidal signals; such "pulsing" maskers produce confusion when the properties of the signal are identical to those of an individual masker "pulse." The level, frequency, and duration of the signal relative to an individual masker pulse, as well as offset-onset delay, were varied to determine the minimum change necessary to eliminate confusion. For maskers composed of 20-ms pulses, confusion was eliminated by changes in signal level of 5 dB or changes in signal frequency of 30 to 40 Hz. For maskers composed of 10-, 20-, or 40-ms pulses, confusion was eliminated by signal delays of 8 to 16 ms or by signal durations less than half or greater than twice the masker-pulse duration. Results with adaptive procedures designed to measure confusion-free or confusion-determined thresholds suggest that confusion effects can be minimized or avoided by extensive listener training with a procedure in which the signal and masker are not presented at similar intensities.


Examining 24-Hour Activity and Sleep Behaviors and Related Determinants in Latino Adolescents and Young Adults With Obesity.
Background. Few studies have examined 24-hour activity and sleep behaviors and their contribution to type 2 diabetes (T2D) in Latino adolescents and young adults with obesity. Aim. This study included quantitative data on T2D risk and 24-hour activity and sleep behaviors and qualitative data on individual, social, and environmental behavioral determinants. Method. A 7 day, 24-hour, wrist-worn accelerometer protocol assessed moderate-to-vigorous physical activity (PA), sedentary behaviors (SB), sleep, and sleep regularity, in adolescents (N = 38; 12-16 years) and young adults (N = 22; 18-22 years). T2D-related outcomes included adiposity (BMI, BF%, waist circumference), fasting, and 2-hour glucose. A subsample of participants (N = 16 adolescents, N = 15 young adults) completed interviews to identify behavioral determinants. Results. High levels of PA were observed among adolescents (M = 103.8 ± 67.5 minutes/day) and young adults (M = 96.8 ± 78.8 minutes/day) as well as high levels of SB across both age groups (≥10 hours/day). Sleep regularity was negatively associated with adiposity (all ps < .05) in both age groups as well as fasting and 2-hour glucose in young adults (all ps < .05). Social support was associated with PA in both age groups as well as SB in younger youth. Auditory noises, lights, and safety inhibited sleep in both age groups. Conclusion. PA is critical for disease reduction, yet reducing SB and improving sleep are also important targets for reducing T2D risk in Hispanic adolescents and young adults. Future health promotion and disease prevention strategies should leverage qualitative findings regarding behavioral determinants.


Genomic effects of IFN-beta in multiple sclerosis patients.
The purpose of this report was to characterize the dynamics of the gene expression cascades induced by an IFN-beta-1a treatment regimen in multiple sclerosis patients and to examine the molecular mechanisms potentially capable of causing heterogeneity in response to therapy. In this open-label pharmacodynamic study design, peripheral blood was obtained from eight relapsing-remitting multiple sclerosis patients just before and at 1, 2, 4, 8, 24, 48, 120, and 168 h after i.m. injection of 30 micro g of IFN-beta-1a. The total RNA was isolated from monocyte-depleted PBL and analyzed using cDNA microarrays containing probes for >4000 known genes. IFN-beta-1a treatment resulted in selective, time-dependent effects on multiple genes. The mRNAs for genes implicated in the anti-viral response, e.g., double-stranded RNA-dependent protein kinase, myxovirus resistance proteins 1 and 2, and guanylate binding proteins 1 and 2 were rapidly induced within 1-4 h of IFN-beta treatment. The mRNAs for several genes involved in IFN-beta signaling, such as IFN-alpha/beta receptor-2 and Stat1, were also increased. The mRNAs for lymphocyte activation markers, such as IFN-induced transmembrane protein 1 (9-27), IFN-induced transmembrane protein 2 (1-8D), beta(2)-microglobulin, and CD69, were also increased in a time-dependent manner. The findings demonstrate that IFN-beta treatment induces specific and time-dependent changes in multiple mRNAs in lymphocytes of multiple sclerosis patients that could provide a framework for rapid monitoring of the response to therapy.


Variability of pulmonary function in alpha-1-antitrypsin deficiency: residual family resemblance beyond the effect of the Pi locus.
To gain insight into the variable expression of lung disease in alpha 1-antitrypsin deficiency, two pulmonary function tests, FEV1 and FEF25-75, were examined in alpha 1-antitrypsin-deficient individuals and their families. The mean and variance effects of Pi type, age, and sex on the pulmonary function variables were removed by stepwise multiple regression, and the residual phenotypes were analyzed. Path analysis of the residual phenotypes with environmental indices in 46 nuclear families demonstrated highly significant cultural inheritance. Significant polygenic inheritance was not demonstrated for FEV1 but was shown for FEF25-75. For FEV1, adjustment for the significant interaction between Pi type and pack-years of smoking tended to increase the estimated contribution of polygenic inheritance and to decrease the estimated contribution of cultural inheritance. Segregation analysis of the residual phenotypes in 44 nuclear families was carried out to determine whether another major gene, other than the Pi locus, may be influencing pulmonary function in this population. Statistical evidence was found for an additional major gene influencing FEV1; however, the evidence diminished after adjusting for the effects of pack-years and the interaction between Pi type and pack-years. This apparent drop in the importance of genetic factors would not be surprising if the effect of the putative major gene is to enhance susceptibility to effects of cigarette smoking. Finally, our investigation demonstrates the feasibility of dissecting residual familial effects on complex multifactorial traits.


'It Opened My Eyes'-examining the impact of a multifaceted chlamydia testing intervention on general practitioners using Normalization Process Theory.
Chlamydia is the most common notifiable sexually transmissible infection in Australia. Left untreated, it can develop into pelvic inflammatory disease and infertility. The majority of notifications come from general practice and it is ideally situated to test young Australians. The Australian Chlamydia Control Effectiveness Pilot (ACCEPt) was a multifaceted intervention that aimed to reduce chlamydia prevalence by increasing testing in 16- to 29-year-olds attending general practice. GPs were interviewed to describe the effectiveness of the ACCEPt intervention in integrating chlamydia testing into routine practice using Normalization Process Theory (NPT). GPs were purposively selected based on age, gender, geographic location and size of practice at baseline and midpoint. Interview data were analysed regarding the intervention components and results were interpreted using NPT. A total of 44 GPs at baseline and 24 at midpoint were interviewed. Most GPs reported offering a test based on age at midpoint versus offering a test based on symptoms or patient request at baseline. Quarterly feedback was the most significant ACCEPt component for facilitating a chlamydia test. The ACCEPt intervention has been able to moderately normalize chlamydia testing among GPs, although the components had varying levels of effectiveness. NPT can demonstrate the effective implementation of an intervention in general practice and has been valuable in understanding which components are essential and which components can be improved upon.


REVIEW: "ISCHEMIC STROKE: From Fibrinolysis to Functional Recovery" Nanomedicine: Emerging Approaches to Treat Ischemic Stroke.
Stroke is responsible for 11% of all deaths worldwide, the majority of which are caused by ischemic strokes, thus making the need to urgently find safe and effective therapies. Today, these can be cured either by mechanical thrombectomy when the thrombus is accessible, or by intravenous injection of fibrinolytics. However, the latter present several limitations, such as potential severe side effects, few eligible patients and low rate of partial and full recovery. To design safer and more effective treatments, nanomedicine appeared in this medical field a few decades ago. This review will explain why nanoparticle-based therapies and imaging techniques are relevant for ischemic stroke management. Then, it will present the different nanoparticle types that have been recently developed to treat this pathology. It will also study the various targeting strategies used to bring nanoparticles to the stroke site, thereby limiting side effects and improving the therapeutic efficacy. Finally, this review will present the few clinical studies testing nanomedicine on stroke and discuss potential causes for their scarcity.


Probabilistic winner-take-all segmentation of images with application to ship detection.
A recent neural clustering scheme called "probabilistic winner-take-all (PWTA)" is applied to image segmentation. It is demonstrated that PWTA avoids underutilization of clusters by adapting the form of the cluster-conditional probability density function as clustering proceeds. A modification to PWTA is introduced so as to explicitly utilize the spatial continuity of image regions and thus improve the PWTA segmentation performance. The effectiveness of PWTA is then demonstrated through the segmentation of airborne synthetic aperture radar (SAR) images of ocean surfaces so as to detect ship signatures, where an approach is proposed to find a suitable value for the number of clusters required for this application. Results show that PWTA gives high segmentation quality and significantly outperforms four other segmentation techniques, namely, 1) K-means, 2) maximum likelihood (ML), 3) backpropagation network (BPN), and 4) histogram thresholding.


Concise review: the role of oxygen in hematopoietic stem cell physiology.
Molecular dioxygen, O(2), is an important element in cellular microenvironment in vivo, and often overlooked in standard in vitro and ex vivo cell culture systems. Molecular oxygen is the ultimate electron acceptor in oxidative cellular respiration, and also a signal that regulates cell fate through concentration gradients. Recent advances in physiology of oxygen and adult stem cell research have shown that apart from being important for oxidative phosphorylation, thus energy metabolism, oxygen is also important as a signaling molecule and an integral part of the stem cell niche. This review article covers the influence of physiologically relevant oxygen levels on adult stem cells through highlighting the research on the effect of oxygen concentration on hematopoietic stem cell maintenance, proliferation and differentiation. This is important particularly to understand the embryonic and adult stem cell biology and physiology. The new discoveries in this field will help to further improve current tissue engineering and clinical applications. In addition, understanding the relationship between oxygen and stemness is invaluable for the advanced treatments of neoplastic diseases. Authors believe that in the future, active and programmed dynamic of oxygen levels will be routinely used for the programmed in vitro and ex vivo expansion of different adult stem cell types and tissue regeneration purposes.


Geographical variation in the risk of H7N9 human infections in China: implications for risk-based surveillance.
The influenza A (H7N9) subtype remains a public health problem in China affecting individuals in contact with live poultry, particularly at live bird markets. Despite enhanced surveillance and biosecurity at LBMs H7N9 viruses are now more widespread in China. This study aims to quantify the temporal relationship between poultry surveillance results and the onset of human H7N9 infections during 2013-2017 and to estimate risk factors associated with geographical risk of H7N9 human infections in counties in Southeast China. Our results suggest that poultry surveillance data can potentially be used as early warning indicators for human H7N9 notifications. Furthermore, we found that human H7N9 incidence at county-level was significantly associated with the presence of wholesale LBMs, the density of retail LBMs, the presence of poultry virological positives, poultry movements from high-risk areas, as well as chicken population density and human population density. The results of this study can influence the current AI H7N9 control program by supporting the integration of poultry surveillance data with human H7N9 notifications as an early warning of the timing and areas at risk for human infection. The findings also highlight areas in China where monitoring of poultry movement and poultry infections could be prioritized.


Pediatric obstructive sleep apnea syndrome.
Pediatric obstructive sleep apnea syndrome (OSAS) is a common health problem diagnosed and managed by various medical specialists, including family practice physicians, pediatricians, pulmonologists, and general and pediatric otolaryngologists. If left untreated, the sequelae can be severe. Over the last decade, significant advancements have been made in the evidence-based management of pediatric OSAS. This article focuses on the current understanding of this disease, its management, and related clinical practice guidelines.


Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer Aged at Least 75 Years: A Post-Hoc Subgroup Analysis of Three Phase II Trials.
Patients older than 75 years of age are usually excluded from metastatic colorectal cancer studies based on a combination chemotherapy containing oxaliplatin. Our group conducted three phase II trials in elderly patients in recent years. A post-hoc subgroup analysis of 67 patients aged at least 75 years was included in this study. Oxaliplatin was combined with capecitabine in two trials and with uracil-tegafur (UFT) plus folinic acid in the third trial. In one study, bevacizumab was also added to chemotherapy. The median age of patients was 77 years, and all had a good performance status (0 to 1). The observed overall response rate was 45%, comparable to younger patients (51%, p = 0.49). The estimated median progression-free survival (PFS) time and overall survival (OS) time were 8.7 and 19.3 months, respectively. These results did not significantly differ from those in younger patients (8.0 months for PFS (p = 0.58) and 19.7 months for OS (p = 0.94), respectively). The most common grade 3-4 adverse events included diarrhea (13%), fatigue (13%), peripheral neuropathy (10%), and neutropenia (7%). Moreover, the toxicity was never statistically different from that in younger patients. The efficacy of oxaliplatin-based combination was maintained in fit elderly patients ≥75 years.


Trait-based signatures of cloud base height in a tropical cloud forest.
Clouds have profound consequences for ecosystem structure and function. Yet, the direct monitoring of clouds and their effects on biota is challenging especially in remote and topographically complex tropical cloud forests. We argue that known relationships between climate and the taxonomic and functional composition of plant communities may provide a fingerprint of cloud base height, thus providing a rapid and cost-effective assessment in remote tropical cloud forests. To detect cloud base height, we compared species turnover and functional trait values among herbaceous and woody plant communities in an ecosystem dominated by cloud formation. We measured soil and air temperature, soil nutrient concentrations, and extracellular enzyme activity. We hypothesized that woody and herbaceous plants would provide signatures of cloud base height, as evidenced by abrupt shifts in both taxonomic composition and plant function. We demonstrated abrupt changes in taxonomic composition and the community- weighted mean of a key functional trait, specific leaf area, across elevation for both woody and herbaceous species, consistent with our predictions. However, abrupt taxonomic and functional changes occurred 100 m higher in elevation for herbaceous plants compared to woody ones. Soil temperature abruptly decreased where herbaceous taxonomic and functional turnover was high. Other environmental variables including soil biogeochemistry did not explain the abrupt change observed for woody plant communities. We provide evidence that a trait-based approach can be used to estimate cloud base height. We outline how rises in cloud base height and differential environmental requirements between growth forms can be distinguished using this approach.


Exploring the impact of renewable energy on economic growth and carbon emissions: Evidence from partial least squares structural equation modeling.
The concern for environmental sustainability comes along with sustainable energy for consumption. Therefore, this study aims to explore the direct and indirect effects of renewable energy on economic growth and carbon emissions by employing Partial Least Square Structure Equation Modeling and Granger Causality Test and the data for this study is from 1990 to 2021. The results from the Partial Least Squares Structure Equation Modeling indicate that renewable energy consumption causes carbon emissions and has no effect on economic growth. Financial inclusion and foreign direct investment have positive effects on carbon emissions. However, renewable energy has an indirect negative effect on carbon emissions through economic growth. Foreign direct investment affects economic growth positively. Furthermore, the results from the Granger causality test indicate that renewable energy has a unidirectional causality relationship with financial inclusion and foreign direct investment and has a feedback causality relationship with economic growth. In addition, there is a feedback causal effect between financial inclusion and carbon emissions, a unidirectional effect running from carbon emissions to foreign direct investment, and a causal effect from economic growth to foreign direct investment. This study has suggested comprehensive policy recommendations for policymakers based on the findings.


[Hygienic evaluation of laser projectors].
Hygienic evaluation covered 11 laser projectors used for theater and entertainment events and providing laser demonstrations. Laser irradiation diffusely reflected from the screen and scattered beyond the limits of zone with laser danger was proved safe.


[Novel mechanism for hepatic lipid accumulation: a physiological role for hepatic PPARγ-fsp27 signal].
Fat-specific protein 27 (fsp27) was originally isolated by screening for genes specifically expressed in fully differentiated mouse adipocytes. Fsp27 and cell death-inducing DFF45-like effector (CIDE) C, the human homologue of fsp27, belong to the CIDE family. Fsp27, which is highly expressed in mouse white and brown adipose tissues, was recently reported to be a lipid droplet (LD)-binding protein that promotes lipid accumulation in adipocytes. In contrast, we showed that fsp27 was also expressed in the fatty liver of the ob/ob type II diabetes model mouse. The expression of fsp27 was markedly decreased in livers lacking the nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ). A functional PPAR response element site was identified in the fsp27 promoter region. Forced expression of fsp27 in hepatocytes in vitro or in vivo led to increased LD through increased triglyceride levels. The current status of the physiological roles of the PPARγ-fsp27 signal in fatty liver are discussed along with its significance as a factor involved in the development of metabolic disorders.


Medical students as junior adverse drug event managers facilitating reporting of ADRs.
The Junior Adverse Drug Event Manager (J-ADEM) team is a multifaceted intervention focusing on real-life education for medical students that has been shown to assist healthcare professionals in managing and reporting suspected adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. The aim of this study was to quantify and describe the ADRs reported by the J-ADEM team and to determine the clinical potential of this approach. The J-ADEM team consisted of medical students tasked with managing and reporting ADRs in hospitalized patients. All ADRs screened and reported by J-ADEM team were recorded anonymously, and categorized and analysed descriptively. From August 2018 through January 2020, 209 patients on two wards in an academic hospital were screened for ADR events. The J-ADEM team reported 101 ADRs. Although most ADRs (67%) were first identified by healthcare professionals and then reported by the J-ADEM team, the team also reported an additional 33 not previously identified serious ADRs. In 10% of all reported ADRs, the J-ADEM team helped optimize ADR treatment. The ADR reports were largely well-documented (78%), and ADRs were classified as type A (66%), had a moderate or severe severity (85%) and were predominantly avoidable reactions (69%). This study shows that medical students are able to screen patients for ADRs, can identify previously undetected ADRs and can help optimize ADR management. They significantly increased (by 300%) the number of ADR reports submitted, showing that the J-ADEM team can make a valuable clinical contribution to hospital care.


Oncoplastic breast surgery for cancer: analysis of 540 consecutive cases [outcomes article].
Synchronous plastic and oncological surgery is undertaken to improve the security of excision margins and yield high-quality aesthetic outcomes when conventional breast-conserving therapy either anticipates poor results or is not possible. A total of 540 consecutive patients underwent primary oncoplastic breast surgery for cancer with high tumor-to-breast volume ratios and locations precluding a good aesthetic result with simple tumor excision. A variety of techniques were employed at the Institut Curie between 1986 and 2007, and aesthetic outcomes were assessed on a five-point scale from 1 (excellent) to 5 (poor). The median age was 52 years (range, 28 to 90 years), and median follow-up was 49 months (6 to 262 months). Median tumor size was 29.1 mm (range, 4 to 100 mm), with most patients (72.3 percent) having a brassiere cup size of B or C. Close or involved margins occurred in 18.9 percent, with mastectomy being necessary in 9.4 percent. A satisfactory aesthetic outcome (ratings of 1 to 3) at 5 years was obtained in 90.3 percent. Five-year overall and distant disease-free survival rates were 92.9 and 87.9 percent, respectively, with local recurrence in 6.8 percent. With local recurrence and survival rates similar to those for breast-conserving therapy, this series confirms the safety of oncoplastic breast surgery for tumors both high in volume and difficult in location. Highly satisfactory cosmetic outcomes extend the indications for conservative surgery, further reduce the mastectomy rate, and limit adverse aesthetic sequelae.


Processing of gaze direction within the N170/M170 time window: A combined EEG/MEG study.
Gaze direction is an important social signal for human beings. Beside the role of gaze in attention orienting, direct gaze (that is, gaze directed toward an observer) is a highly relevant biological stimulus that elicits attention capture and increases face encoding. Brain imaging studies have emphasized the role of the superior temporal sulcus (STS) in the coding of gaze direction and in the integration of gaze and head cues of social attention. The dynamics of the processing and integration of these cues remains, however, unclear. In order to address this question, we used deviated and frontal faces with averted and direct gaze in a combined electro- and magneto- encephalography (EEG-MEG) study. We showed distinct effects of gaze direction on the N170 and M170 responses. There was an interaction between gaze direction and head orientation between 134 and 162ms in MEG and a main effect of gaze direction between 171 and 186ms in EEG. These effects involved the posterior and anterior regions of the STS respectively. Both effects also emphasized the sensitivity to direct gaze. These data highlight the central role of the STS in gaze processing.


Scaling and power-laws in ecological systems.
Scaling relationships (where body size features as the independent variable) and power-law distributions are commonly reported in ecological systems. In this review we analyze scaling relationships related to energy acquisition and transformation and power-laws related to fluctuations in numbers. Our aim is to show how individual level attributes can help to explain and predict patterns at the level of populations that can propagate at upper levels of organization. We review similar relationships also appearing in the analysis of aquatic ecosystems (i.e. the biomass spectra) in the context of ecological invariant relationships (i.e. independent of size) such as the 'energetic equivalence rule' and the 'linear biomass hypothesis'. We also discuss some power-law distributions emerging in the analysis of numbers and fluctuations in ecological attributes as they point to regularities that are yet to be integrated with traditional scaling relationships and which we foresee as an exciting area of future research.


Calcite-accumulating large sulfur bacteria of the genus Achromatium in Sippewissett Salt Marsh.
Large sulfur bacteria of the genus Achromatium are exceptional among Bacteria and Archaea as they can accumulate high amounts of internal calcite. Although known for more than 100 years, they remain uncultured, and only freshwater populations have been studied so far. Here we investigate a marine population of calcite-accumulating bacteria that is primarily found at the sediment surface of tide pools in a salt marsh, where high sulfide concentrations meet oversaturated oxygen concentrations during the day. Dynamic sulfur cycling by phototrophic sulfide-oxidizing and heterotrophic sulfate-reducing bacteria co-occurring in these sediments creates a highly sulfidic environment that we propose induces behavioral differences in the Achromatium population compared with reported migration patterns in a low-sulfide environment. Fluctuating intracellular calcium/sulfur ratios at different depths and times of day indicate a biochemical reaction of the salt marsh Achromatium to diurnal changes in sedimentary redox conditions. We correlate this calcite dynamic with new evidence regarding its formation/mobilization and suggest general implications as well as a possible biological function of calcite accumulation in large bacteria in the sediment environment that is governed by gradients. Finally, we propose a new taxonomic classification of the salt marsh Achromatium based on their adaptation to a significantly different habitat than their freshwater relatives, as indicated by their differential behavior as well as phylogenetic distance on 16S ribosomal RNA gene level. In future studies, whole-genome characterization and additional ecophysiological factors could further support the distinctive position of salt marsh Achromatium.


Economic impact of standard antibiotic therapy combined with amikacin, in clinical unit, Lodz, Poland--part II.
The study "Alexander" on bacterial resistance to antibiotics conducted in Poland revealed high sensitivity of bacterial strains to simple and cheap antibiotics. In Poland pharmacoeconomic studies on the safety, effectiveness and costs of treatment are rare. Development of therapeutic standards in bacterial infections on the basis of pharmacoeconomic analyses and clinical studies determining effectiveness and safety of therapy allows for more rational pharmacotherapy. The following problems were investigated: is the treatment of serious bacterial infections with cheap standard antibiotics [SAT] or other antibiotics therapy [OAT] combined with amikacin safe and effective? What are the direct costs? How can reduction in costs be achieved? Prospective, randomized, single-blind study was performed in the group of 152 patients, admitted from 1 January to 31 July 2000, treated with amikacin combined with aminopenicillin/amoxicillin [SAT] versus other antibiotic therapy [OAT]. The economic evaluation was done by estimation of direct cost of treatment in patients with risk factors of nephrotoxicity [NT] and therapeutic drug monitoring [TDM] versus without TDM. The statistical significance was evaluated. This study revealed that effectiveness of the SAT versus OAT combined with amikacin in serious infections is high, 80% vs. 87%, respectively. Amikacin used in high once daily dose [HODD] in combined therapy with SAT or OAT was more safe in patients with risk of nephrotoxicity and TDM (21%) vs without TDM (10%) than used in conventional therapy [CT] 40% vs 19% [p < 05]. Evaluation of the absolute risk of nephrotoxicity increase in patients with TDM was 0.16 vs 0.34 Absolute Risk Increase (ARI) 0.18, Relative Risk Reduction (RRR): 0.53; 95% Confidence Interval (CI): 0.87-2.82. The number needed to tread (NNT): 5.43; reduction of the risk of nephrotoxicity in patients without TDM treated with HODD was 0.19 vs 0.09, Absolute Risk Reduction (ARR): 0.09; RRR: 0.47; 95% CI: 0.74-1.34; NNT: 11.1; reduction of the risk of nephrotoxicity in patients with TDM treated with amikacin HODD was 0.21 vs 0.40, ARR: 0.19; RRR: 0.48; 95% CI: 0.68-1.74; NNT: 5.3; Direct costs of the treatment with SAT vs OAT combined with amikacin are low [EU 78.30 vs EU 145.16] in the Clinical Unit of Lodz, compared with other countries. Out of EU 530 for the hospitalization of one patient, 86% constituted "hotel costs". Omitting TDM in patients without risk factors can significantly decrease costs by EU 66 860 per 1000 patients. Introduction of safe and cheap standard in the treatment of bacterial infections in clinical unit, shortening hospitalization by 5 days and limiting the number of patients requiring TDM service allows for a decrease in direct cost of about EU 235410 per 1000 patients/year.


Neurological and psychological mechanisms of the specific and nonspecific effects of acupuncture on knee osteoarthritis: study protocol for a randomized, controlled, crossover trial.
Acupuncture, as one of the promising non-pharmacological interventions, has been proved to be beneficial for patients. However, the magnitude of acupuncture's specific and nonspecific effects, as well as their neurological and psychological determinants, remains unclear. Therefore, this study is designed to examine the acupuncture efficacy, investigate whether the brain mechanisms between the specific and nonspecific effects of acupuncture are different, and to evaluate how psychological factors affect the acupuncture effects. This is a randomized, controlled, crossover clinical trial. A total of 60 patients with knee osteoarthritis will receive 4 weeks of acupuncture treatment and 4 weeks of sham acupuncture treatment in a random order separated by a washout period of 2 weeks. The changes in clinical characteristics based on pain-related scales will be assessed to investigate the clinical efficacy of acupuncture. Resting state functional magnetic resonance imaging (fMRI) scans will be used to identify the brain activity changes related to the specific and nonspecific effects of acupuncture. The questionnaires of psychological factors will be used to evaluate patients' psychological properties. Correlation and mediation analyses will be conducted among psychological factors, brain activity changes, and symptoms improvement to explore the neurological and psychological correlates of the acupuncture effects. This study will concentrate on distinguishing and clarifying the specific and nonspecific effects of acupuncture. The results of this study may contribute to rationally optimize the acupuncture therapies by flexible application of the specific and nonspecific effects of acupuncture. Chinese Clinical Trial Registry ChiCTR1900025807 . Registered on 9 September 2019.


An annotated video dataset for computing video memorability.
Using a collection of publicly available links to short form video clips of an average of 6 seconds duration each, 1275 users manually annotated each video multiple times to indicate both long-term and short-term memorability of the videos. The annotations were gathered as part of an online memory game and measured a participant's ability to recall having seen the video previously when shown a collection of videos. The recognition tasks were performed on videos seen within the previous few minutes for short-term memorability and within the previous 24 to 72 hours for long-term memorability. Data includes the reaction times for each recognition of each video. Associated with each video are text descriptions (captions) as well as a collection of image-level features applied to 3 frames extracted from each video (start, middle and end). Video-level features are also provided. The dataset was used in the Video Memorability task as part of the MediaEval benchmark in 2020.


Operation Iraqi Freedom/Operation Enduring Freedom: exploring wartime death and bereavement.
Military deaths are often sudden, unanticipated, traumatic, and/or violent in nature and involve the death of a young adult. More than 5,500 service members have died as a result of their service in the wars in Afghanistan (2001) and Iraq (2003) in combat- or non-combat- related incidences. As the death toll continues to rise, service members and their families struggle with the visible and invisible wounds of war. This article explores wartime death, trauma, and bereavement experienced by those survivors affected by service members who have died as a result of their military service in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). It recognizes the circumstantial and cultural factors of the death as well as the grief and trauma experiences of survivors. Resources and suggested interventions of support are highlighted.


Synthetic phospho-oligosaccharide fragments of lipophosphoglycan as acceptors for Leishmania major alpha-D-mannosylphosphate transferase.
Protozoan parasites of the genus Leishmania synthesise lipophosphoglycans, phosphoglycans and proteophosphoglycans that contain phosphosaccharide-repeat units of [-6Gal beta 1-4Man alpha 1-P-]. In this study, a GDP-Man-dependent alpha-mannosylphosphate-transferase activity was detected in washed Leishmania major membranes using synthetic phospho-oligosaccharide fragments of lipophosphoglycan as acceptor substrates. The divalent-cation-dependent alpha-mannosylphosphate-transferase activity had an apparent K(m) for GDP-Man of about 15-20 microM and a pH optimum of 7.0. The activity showed a requirement for a non-reducing terminal beta Gal residue and for one or more phosphodiester units preceding the acceptor site. Based on these results, the activity may be defined as a GDP-Man: Gal beta 1-4Man alpha 1-P-R alpha-mannosylphosphate-transferase. This acceptor specificity is consistent with a role for the alpha-mannosylphosphate transferase in the elongation of phosphosaccharide-repeat domains of Leishmania glycoconjugates rather than in the priming of these domains. An identical or similar activity must exist in the amastigote forms of the Leishmania that produce and secrete proteophosphoglycan material and the activity therefore represents a feasible target for the development of chemotherapeutics.


Surgeon-tool force/torque signatures--evaluation of surgical skills in minimally invasive surgery.
The best method of training for laparoscopic surgical skills is controversial. Some advocate observation in the operating room, while others promote animal and simulated models or a combination of surgical related tasks. The mode of proficiency evaluation common to all of these methods has been subjective evaluation by a skilled surgeon. In order to define an objective means of evaluating performance, an instrumented laparoscopic grasper was developed measuring the force/torque at the surgeon hand/tool interface. The measured database demonstrated substantial differences between experienced and novice surgeon groups. Analyzing forces and torques combined with the state transition during surgical procedures allows an objective measurement of skill in MIS. Teaching the novice surgeon to limit excessive loads and improve movement efficiency during surgical procedures can potentially result in less injury to soft tissues and less wasted time during laparoscopic surgery. Moreover the force/torque database measured in this study may be used for developing realistic virtual reality simulators and optimization of medical robots performance.


Local GDNF expression mediated by lentiviral vector protects facial nerve motoneurons but not spinal motoneurons in SOD1(G93A) transgenic mice.
Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are associated with mutations in the cytosolic Cu/Zn superoxide dismutase 1 (SOD1) gene. Transgenic SOD1 mice constitute useful models of ALS to screen therapeutical approaches. Glial cell line-derived neurotrophic factor (GDNF) holds promises for the treatment of motoneuron disease. In the present study, GDNF expression in motoneurons of SOD1(G93A) transgenic mice was assessed by facial nucleus or intraspinal injection of lentiviral vectors (LV) encoding GDNF. We show that lentiviral vectors allow the expression for at least 12 weeks of GDNF that was clearly detected in motoneurons. This robust intraspinal expression did, however, not prevent the loss of motoneurons and muscle denervation of transgenic mice. In contrast, LV-GDNF induced a significant rescue of motoneurons in the facial nucleus and prevented motoneuron atrophy. The differential effect of GDNF on facial nucleus versus spinal motoneurons suggests different vulnerability of motoneurons in ALS.


Ultrasonography and CT findings of a dermoid cyst of the cecum. A case report.
We report the US and CT findings of a dermoid cyst of the cecum, which is a very uncommon location for this entity. Pathological correlation and differential diagnosis are briefly discussed.


Inability of toxin inhibitors to neutralize enhanced toxicity caused by bacteria adherent to tissue culture cells.
Toxicity to Y-1 adrenal mouse cells caused by heat-labile toxin secreted by an enterotoxigenic strain of Escherichia coli (H-10407-p) was 40-fold enhanced in mixtures containing organisms capable of adhering to the Y-1 cells compared with monolayers exposed to organisms whose adherence was inhibited by mannoside. Severalfold the concentrations of anti-heat-labile toxin antibodies required to neutralize the toxicity of nonadherent bacteria were unable to neutralize the toxicity caused by adherent bacteria. The cytolytic activity toward tissue culture cells and mouse peritoneal macrophages caused by streptolysin S carried by Streptococcus pyogenes was severalfold increased in mixtures containing organisms capable of adhering to the target cells compared with mixtures containing nonadherent bacteria. The ability of trypan blue and RNA core to inhibit the cell-bound streptolysin S was determined in tissue culture cells containing adherent streptococci and mixtures of streptococci randomly colliding with erythrocytes. Both inhibitors were markedly less effective in neutralizing cytolysis than in their ability to neutralize hemolysis. We conclude that compared with toxins produced by nonadherent bacteria, those produced by bacteria adherent to cells are targeted more efficiently and become relatively inaccessible to neutralization by toxin inhibitors.


Cell death markers in patients with cirrhosis and acute decompensation.
The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC (CLIF Acute-on-Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase-cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme-linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score in prediction of progression from AD to ACLF (P < 0.05). Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure. (Hepatology 2018;67:989-1002).


Attraction of parasitic wasps by caterpillar-damaged plants.
Plant volatiles emitted in response to herbivory have been suggested to function as signals to attract natural enemies of herbivores. Most known examples of induced plant volatiles used by natural enemies involve parasitoids that locate caterpillars by means of odours emitted by plants after caterpillar attack. We study the tritrophic system that comprises the parasitoid Cotesia marginiventris, host caterpillars from the genus Spodoptera, and maize plants. Among the volatiles emitted by caterpillar-damaged maize plants, sesquiterpenes and indole are particularly attractive to the parasitoid. The usefulness of these plant volatiles for parasitoids is obvious. Less clear is their benefit to plants that emit them, as in most cases parasitization does not immediately stop caterpillars from damaging plants. However, plants appear to benefit directly from attracting C. marginiventris, as parasitized caterpillars consume considerably less plant tissue than unparasitized caterpillars. It is expected that in systems where parasitoids significantly reduce herbivory, they have contributed to selective pressures that have shaped the phenomenon of herbivore-induced volatile emissions by plants.


Wire Roughness Assessment of 0.016'' × 0.022'' the Technique Lingual Orthodontics.
To evaluate the difference in surface roughness of stainless steel archwires of different commercial brands used in lingual orthodontics. Precontoured arches measuring 0.016'' × 0.022'' were selected of the following brands: Tecnident, Adenta, G&H, Highland Metals Inc., Ormco, Incognito, and Ebraces. Quantitative evaluation of the surface roughness of archwires was performed by means of an atomic force microscope in contact mode. Three surface readouts were taken of each sample, analyzing areas of 20 × 20 μm. Each scan of the samples produced a readout of 512 lines, generating three-dimensional images of the wires. The analysis of variance statistical test was applied to prove significant variables (p > 0.05), with H0 being rejected and H1 accepted. The Incognito brand showed the lowest surface roughness. The archwires of brands Adenta, Tecnident, Highland, and Ormco showed similar values among them, and all close to these obtained by the Incognito brand. The archwires of the Ebraces brand showed the highest surface roughness, with values being close to those of the G&H Brand. There was a statistical difference in surface roughness of orthodontic archwires among the brands studied. Companies should pay attention to the quality control of their materials, as these may directly affect the quality of orthodontic treatment.


The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.
The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. NCT00018255.


PCR quantification of SiO₂ particle uptake in cells in the ppb and ppm range via silica encapsulated DNA barcodes.
There is a strong interest in studying the cellular uptake of silica nanoparticles, particularly at medically relevant concentrations (ppb-ppm range) to understand their toxicology. At present, uptake analysis at these exposure levels is impeded by the high silica background concentration. Here we describe the use of DNA encapsulated within silica particles as a tool to quantify silica nanoparticles in in vitro cell-uptake experiments at low concentrations (down to 10 fg cell(-1)).


Sleep preferentially enhances memory for emotional components of scenes.
Central aspects of emotional experiences are often well remembered at the expense of background details. Previous studies of such memory trade-offs have focused on memory after brief delays, but little is known about how these components of emotional memories change over time. We investigated the evolution of memory for negative scenes across 30 min, 12 daytime hours spent awake, and 12 nighttime hours including sleep. After 30 min, negative objects were well remembered at the expense of information about their backgrounds. Time spent awake led to forgetting of the entire negative scene, with memories of objects and their backgrounds decaying at similar rates. Sleep, in contrast, led to a preservation of memories of negative objects, but not their backgrounds, a result suggesting that the two components undergo differential processing during sleep. Memory for a negative scene develops differentially across time delays containing sleep and wake, with sleep selectively consolidating those aspects of memory that are of greatest value to the organism.


[Comparative evaluation of the anti-anginal effects of dilzem and corinfar in patients with ischemic heart disease and exertion-induced stenocardia].
Antianginal efficiency of dilzem, as compared to placebo, was assessed in 53 patients with angina of effort, functional class II-IV. Repeated bicycle ergometry and 24-hour ECG monitoring were used as objective methods for the assessment of treatment efficiency. Antianginal effect of dilzem (180-300 mg/daily) was compared to that of corinfar (30-60 mg/daily) in 16 patients by a simple blind cross procedure, using placebo. The duration of continuous bicycle ergometric exercise increased by 163 sec. In the presence of dilzem, and by 152 sec. in the presence of corinfar, as compared to the placebo, while the performance volume increased by 1296 and 1188 kgm, respectively (p less than 0.001). Unlike corinfar, dilzem produced a significant drop in heart rate and double product both at rest and during exercise. Both dilzem and corinfar considerably reduced average rate and total duration of painless episodes of myocardial ischemia (p less than 0.05), as evidenced by Holter's monitoring.


Assessment of ribozyme cleavage efficiency using reverse transcriptase real-time PCR.
Real-time PCR is a novel technology recently described to perform quantitative analysis of amplified products. Unlike classical quantitative PCR, this method is easy to standardize, does not required extensive manipulation, and is not reagent intensive, so that the risk of contamination is minimized. Therefore, we have chosen reverse transcriptase real-time PCR to quantitate CD95 (Fas) transcripts to test the cleavage efficiency of anti-Fas ribozymes in the mouse insulinoma cell line beta TC-3. Based on the melting-curve analysis of the amplified products, we determined the temperature at which to collect the fluorescent data used for quantification. After constructing a standard curve by plotting the log of the standards' copy number versus their fractional cycle number, the copy numbers of the unknown samples were automatically determined by interpolation of this curve. As we illustrate in this study, it is important, particularly while setting up the technique, to validate the melting-curve profile with standard gel electrophoresis analysis, achieved by matching melting temperature and size of the amplified product. The method is fast and reproducible: Excluding the isolation of RNA and synthesis of cDNA, the results can be obtained in less than 1 hr. The coefficient of variance is 15% in the range of 10(4)-10(6) gene copies. Accordingly, reverse transcriptase (RT) real-time PCR is a technique suitable for screening a large number of ribozymes.


Tetrahydrocurcumin reduces oxidative stress-induced apoptosis via the mitochondrial apoptotic pathway by modulating autophagy in rats after traumatic brain injury.
Tetrahydrocurcumin (THC) has been identified as a multi-functional neuroprotective agent in numerous neurological disorders. Oxidative stress as a result of injury may induce neuronal apoptosis after traumatic brain injury (TBI). Treatment with THC may improve neurological function following TBI by attenuating oxidative stress and apoptosis and by enhancing autophagy. The purpose of this study was to investigate the mechanism of neuroprotection by THC against oxidative stress-induced neuronal apoptosis after TBI. We hypothesized that neuroprotection by THC may involve modulation of autophagy and the mitochondria apoptotic pathway. We used western blot analysis to evaluate the effect of THC on proteins involved in mitochondrial autophagy and apoptosis after TBI. The terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunofluorescence staining were used to confirm the role of THC in apoptosis and autophagy, respectively. THC-induced neuroprotection was assessed by neurological severity scoring (NSS) and by measuring the brain water content. We demonstrated that treatment with THC increased expression of autophagy-associated proteins LC3-II and Beclin-1 at 24 h post-TBI. Treatment with THC also reduced expression of malondialdehyde (MDA) and increased glutathione peroxidase (GPx) activity. Further, treatment with THC attenuated apoptosis by modulating mitochondrial apoptosis and reducing oxidative stress. Treatment with 3-methyladenine (3-MA) mitigated autophagy activation and reversed the inhibitory effect of THC on the translocation of Bax to the mitochondrial membrane. Moreover, treatment with THC improved neurological function and reduced the brain water content in rats after TBI. We concluded that the neuroprotective effects of THC are mediated by enhancing autophagy activation and by attenuation of oxidative stress and apoptosis after TBI, probably by modulating the mitochondrial apoptotic pathway. We suggest that THC may be an effective therapeutic agent to treat TBI.


First report of a Copitarsia species (Lepidoptera. Noctuidae) damaging soybean crops, with identification key to most common pest species.
The genus Copitarsia Hampson (Lepidoptera. Noctuidae) includes agricultural pests of at least 48 crop plants and they are distributed from Mexico to southern South America. In South America, from Venezuela to Chile and Argentina, Copitarsia incommoda (Walker) is one of the most economic important species of the genus. In this work, we record for the first time for Copitarsia, and specifically for C. incommoda, larvae feeding on soybean leaves and beans. Also, this species is recorded for the first time for Argentina, feeding on lucerne crops. Finally, we provide a larval identification key for most common noctuoids soybean pests of South America, including C. incommoda. This will be helpful for identify this species in soybean crops without the need of larvae rearing.


[Mathematical description of synergistic interactions of environment temperature and microwaves for animal warming].
For mathematical description of synergetic interaction of high environmental temperature and microwaves for animal heating, a simple semi-empirical model was used. In the model, it is suggested that the mechanism of synergistic interaction is caused by the additional effective damages resulting in more higher body temperature increment comparing with that expected for the independent action of each agents. These additional damages are supposed to be produced by the interaction of sublesions induces by each agent and which are ineffective for their separate action. Utilizing the results published for rabbits [15], it was demonstrated that the model describes experimental data, predicts the highest synergistic effect and the condition under which it can be achieved. The data obtained may be useful for the assessment of microwave exposure safe levels.


Light at night and breast cancer risk among California teachers.
There is convincing evidence that circadian disruption mediated by exposure to light at night promotes mammary carcinogenesis in rodents. The role that light at night plays in human breast cancer etiology remains unknown. We evaluated the relationship between estimates of indoor and outdoor light at night and the risk of breast cancer among members of the California Teachers Study. Indoor light-at-night estimates were based on questionnaire data regarding sleep habits and use of nighttime lighting while sleeping. Estimates of outdoor light at night were derived from imagery data obtained from the US Defense Meteorological Satellite Program assigned to geocoded addresses of study participants. Analyses were conducted among 106,731 California Teachers Study members who lived in California, had no prior history of breast cancer, and provided information on lighting while sleeping. Five thousand ninety-five cases of invasive breast cancer diagnosed 1995-2010 were identified via linkage to the California Cancer Registry. We used age-stratified Cox proportional hazard models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for breast cancer risk factors and neighborhood urbanization and socioeconomic class. An increased risk was found for women living in areas with the highest quintile of outdoor light-at-night exposure estimates (HR = 1.12 [95% CI = 1.00-1.26]; test for trend, P = 0.06). Although more pronounced among premenopausal women (HR = 1.34 [95% CI = 1.07-1.69]; test for trend, P = 0.04), the associations did not differ statistically by menopausal status (test for interaction, P = 0.34). Women living in areas with high levels of ambient light at night may be at an increased risk of breast cancer. Future studies that integrate quantitative measurements of indoor and outdoor light at night are warranted.


The effect of quinine on the electroretinograms of children with pediatric cerebral malaria.
To investigate the effects of quinine on the electroretinograms (ERGs) of children with cerebral malaria (CM), we recruited subjects during a single malaria season in Blantyre, Malawi. Seventy ERG investigations were performed, on 34 children with CM. Time recorded from completion of the most recent quinine infusion was termed "quinine elapsed time" (QET). In a subgroup of 16 children, whole-blood quinine concentrations were estimated in a sample of capillary blood, for validation. A significant positive association was found between QET and both maximal-response A-wave amplitude (MRAWA; P=.03) and cone A-wave amplitude (P=.04). Longitudinal analysis demonstrated a significant trend of increasing MRAWA with increasing QET (P=.03). Parenteral quinine administered in therapeutic doses to a pediatric population appears to cause a transient depression in photoreceptor function. No evidence of ocular quinine toxicity was found at the therapeutic doses used.


Monitoring mRNA Half-Life in Arabidopsis Using Droplet Digital PCR.
mRNA decay is an important process in post-transcriptional regulation; in addition, it plays a crucial role in plant development and response to stress. The development of new tools to quantify mRNA decay intermediates is thus important to better characterize the dynamic of mRNA decay in various conditions. Here, we applied droplet digital PCR (ddPCR), a recent and precise PCR technology, to determine mRNA half-life in Arabidopsis seedlings. We demonstrated that ddPCR can correctly assess mRNA half-life from a wide variety of transcripts in a reproducible manner. We also demonstrated that thanks to multiplexing mRNA, the half-life of multiple transcripts can be followed in the same reaction. As ddPCR allows precise quantification, we proposed that this approach is highly suitable when a low amount of RNA is available; for the detection of many targets or for the analysis of lowly expressed transcripts.