Amplatzer vascular plug for occlusion of parent artery in carotid blowout with active extravasation.
Carotid blowout is a devastating complication in patients with head and neck malignancy. Various treatments including high risk surgery, carotid stenting or carotid occlusion using either coils or detachable balloons have been described. The key for any treatment is the rapidity at which it can be performed. We describe treatment of common carotid blowout secondary to neoplastic infiltration using four Amplatzer vascular plugs deployed in less than ten minutes.


Comparison of technetium-99m MAG3 with iodine-131 hippuran by a simultaneous dual channel technique.
Technetium-99m MAG3, a technetium-labeled analog of hippuran, was compared with [131I] hippuran using a simultaneous dual isotope study in 20 patients. The plasma clearance for MAG3 was lower than that of hippuran, but its plasma concentration was higher, resulting in similar rates of excretion and similar renal time-activity curves. Apart from better statistics with the technetium-labeled agent, there were no clinically significant differences in this group of patients.


Current recommendations for prevention of cardiovascular disease in patients with diabetes mellitus. Part II of II.
Patients with diabetes mellitus are at a high risk of developing cardiovascular disease, and therefore stand to benefit greatly from a preventive strategy. Recommendations regarding assessment and management of traditional risk factors are basically similar for diabetic and nondiabetic patients with several important differences. Several nontraditional risk factors also play a substantial role in the development of cardiovascular disease in diabetic patients, and need to be addressed if full preventive care is to be provided. In this second in a two-part series, we present current recommendations for reducing the risk of cardiovascular disease in the diabetic patient.


An alternative to thought suppression?
Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.


[A pilot study on a quality improvement plan with systematic nutritional screening in patients admitted to a regional hospital].
A pilot study to assess the feasibility of implementing a hospital protocol for systematic nutritional screening of admitted patients. Descriptive cross-sectional study. Patients admitted to the Orthopedic Surgery Department of the Regional Hospital of Alcañiz were systematically included within the first 48 hours of hospitalization, from February to September of 2007. The screening methods used were the Nutritional Risk Index (NRI), the CONUT Nutritional Control system, and an indicator based on SENPE recommendations. The need for nutritional support was defined as the presence of any of the following instances: moderate to severe hyponutrition according to the NRI or CONUT methods, or hyponutrition according to the adapted SENPE recommendations. 36.4% of the patients assessed need nutritional support. The rate of hyponutrition according to CONUT is 13.6%, by SENPE criteria is 27.3%, and by the NRI 29.5%. The inter-method agreement is statistically significant and clinically acceptable: Kappa between NRI and CONUT 0.547, between NRI and SENPE 0.609, and between CONUT and SENPE 0.593. The implementation of a structured protocol for collecting the anthropometrical and biochemical parameters implicating a multidisciplinary hospital team enables identifying those patients in whom appropriate nutritional support may improve their prognosis during hospital stay.


Simultaneous Quantification of Opioids in Blood and Urine by Gas Chromatography-Mass Spectrometer with Modified Dispersive Solid-Phase Extraction Technique.
Common methodologies such as liquid-liquid extraction and solid-phase extraction are applied for the extraction of opioids from biological specimens i.e., blood and urine. Techniques including LC-MS/LC-MSMS, GC-MS, etc. are used for qualitative or quantitative determination of opioids. The goal of the present work is to design a green, economic, rugged, and simple extraction technique for famous opioids in human blood and urine and their simultaneous quantification by GC-MS equipped with an inert plus electron impact (EI) ionization source at SIM mode to produce reproducible and efficient results. Morphine, codeine, 6-acetylmorphine, nalbuphine, tramadol and dextromethorphan were selected as target opioids. Anhydrous Epsom salt was applied for dSPE of opioids from blood and urine into acetonitrile extraction solvent with the addition of sodium phosphate buffer (pH 6) and n-hexane was added to remove non-polar interfering species from samples. BSTFA was used as a derivatizing agent for GC-MS. Following method validation, the LOD/LLOQ and ULOQ were determined for morphine, codeine, nal-buphine, tramadol, and dextromethorphan at 10 ng/mL and 1500 ng/mL, respectively, while the LOD/LLOQ and ULOQ were determined for 6-acetylmorphine at 5 ng/mL and 150 ng/mL, respectively. This method was applied to real blood and urine samples of opioid abusers and the results were found to be reproducible with true quantification.


An examination of critical care nurses' knowledge and attitudes regarding pain management in hospitalized patients.
The purpose of this study was to determine the effectiveness of an educational intervention focused on pain management. The sample consisted of 30 medical/surgical intensive care nurses (age range, 23 to 62 years) employed in a large metropolitan hospital in the southeastern United States. McCaffery and Ferrell's Nurses' Knowledge and Attitude Survey Regarding Pain was administered at 2 points in time: before and after the educational program. The survey simultaneously measures knowledge and attitude levels regarding pain control. The paired t test was used to test for differences between pre- and posttest scores. The Point-biserial and Spearman's correlation coefficients were computed to examine relationships between selected sociodemographic variables and scores (baseline and change) on the survey. Results revealed a significant increase in scores after the educational intervention (t = 9.60. p = .0005). Additionally, a statistically significant correlation was found between change scores (posttest minus pretest scores) and years of nursing experience (rs = .37, p = .047). However, no significant relationships were found between type of nursing degree and baseline or change scores (rpb = .11, p = .575; rpb = .01, p = .955). These results support previous research findings related to the problem of inadequate pain management in the hospital setting. Further, the findings indicate that education regarding pain control is crucial for current nursing students as well as practicing nurses. The challenge for nurses is to be responsive to and integrate current pain management techniques in an effort to decrease the discomfort of hospitalized patients.


Machine Learning-Based Modeling of Olfactory Receptors in Their Inactive State: Human OR51E2 as a Case Study.
Atomistic-level investigation of olfactory receptors (ORs) is a challenging task due to the experimental/computational difficulties in the structural determination/prediction for members of this family of G-protein coupled receptors. Here, we have developed a protocol that performs a series of molecular dynamics simulations from a set of structures predicted de novo by recent machine learning algorithms and apply it to a well-studied receptor, the human OR51E2. Our study demonstrates the need for simulations to refine and validate such models. Furthermore, we demonstrate the need for the sodium ion at a binding site near D2.50 and E3.39 to stabilize the inactive state of the receptor. Considering the conservation of these two acidic residues across human ORs, we surmise this requirement also applies to the other ∼400 members of this family. Given the almost concurrent publication of a CryoEM structure of the same receptor in the active state, we propose this protocol as an in silico complement to the growing field of ORs structure determination.


Anti-inflammatory effects of the prostacyclin analogue iloprost in an in vitro model of inflamed human dental pulp cells.
Iloprost's anti-inflammatory effects on human dental pulp stem cells (HDPCs) are currently unknown. We hypothesized that iloprost could downregulate the expression of inflammatory-related genes and protein in an inflamed HDPC in vitro model. To induce inflammation, the HDPCs were treated with a cocktail of interleukin-1 beta, interferon-gamma, and tumour necrosis alpha, at a ratio of 1:10:100. Iloprost (10-6 M) was then added or not to the cultures. Interleukin-6 (IL-6) and interleukin-12 (IL-12) mRNA expression were assessed by real-time polymerase chain reaction. IL-6 protein expression was assessed by enzyme-linked immunosorbent assay. The results were analysed using one-way ANOVA or the Kruskal-Wallis test. The cytokine cocktail induced more robust IL-6 expression than LPS treatment. Iloprost slightly, yet significantly, downregulated IL-6 and IL-12 mRNA expression. These findings suggest that iloprost might be used as a beneficial component in vital pulp therapy.


Endothelium-dependent, shear-induced vasodilation is rate-sensitive.
To quantify the relative contributions of the rate of change and the magnitude of shear stress to endothelium-mediated arteriolar dilation. A feedback control system was designed in which shear stress (tau) and the temporal shear gradient (TSG) were prescribed and dynamically controlled in isolated rat cremaster 1A arterioles. The TSG was the quotient of the maximum shear stress and the ramp duration. This system was used to assess the roles of tau and TSG in the initial, transient vasodilations and the secondary, sustained vasodilations in response to steps and ramps in shear stress. Both step- and ramp-shear experiments revealed time-dependent hiphasic vasodilations that we report for the first time. Application of a step-shear stress of 20 dynes/cm2 elicited an initial transient vasodilation that peaked at about 4 min. When the shear stress was applied as a ramp that reached the maximum value of 20 dynes/cm2 over 5 min, a vasodilation was observed over the ramp period, which reached a peak at the end of the ramp period that was much lower than that observed after step shear. After 20 dynes/cm2 was attained, the vessel diameter decreased despite constant maintenance of the maximum shear stress. In both step- and ramp-shear experiments, after the decrease of the initial vasodilation, a second phase of vasodilation began approximately 15 min after the beginning of the shear application. The second phase of vasodilation reached a steady state that was essentially the same for both the step and the ramp shear. By refining the ramping apparatus further, we varied the TSG up to 40 dynes/cm2 per second and showed that the early vasodilation was highly rate sensitive to TSGs greater than 5 dynes/cm2 per second for a given intermediate value of final shear stress (20 dynes/cm2) and was magnitude sensitive when shear was increased gradually (TSG < 5 dynes/cm2 per second). Our results suggest that two fundamentally different responses to shear stress are mediated by microvascular endothelium: one vasodilation is elicited by shear stress changes on a time scale of a few seconds or less and another is elicited by shear stress changes on a longer time scale. The former response is potent, transient, and rate sensitive; the latter is more modest, sustained, and magnitude sensitive.


Detection of Staphylococcus lugdunensis by a new species-specific PCR based on the fbl gene.
Staphylococcus lugdunensis are unusually virulent coagulase-negative staphylococci associated with skin infections and endocarditis. We developed an accurate and simple PCR assay to identify S. lugdunensis isolates based on detection of the fbl gene, which encodes a fibrinogen-binding protein involved in pathogen adhesion. The PCR assay was established using 16 reference strains of different Staphylococcus species and further validated with a collection of 63 clinical staphylococcal isolates that were also phenotypically characterized. Reliable results for the detection of S. lugdunensis isolates were obtained for 100% of the strains evaluated, indicating that this PCR assay can be used in the routine of microbiology laboratories as one more tool for correct species differentiation.


Antimicrobial prophylaxis in adults.
Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost.


Calcified pleural plaque mimicking a traumatic pneumothorax.
Pneumothorax is a common presentation to the emergency department, arising from traumatic and non-traumatic aetiologies. Diagnosis of non-tension pneumothorax is by a visible lung edge on chest radiography together with the absence of lung markings more peripherally. The Advanced Trauma Life Support (ATLS) system recommends tube thoracostomy as the definitive treatment for traumatic pneumothorax. The case is described of a patient who presented following thoracic trauma with an unusual finding on chest radiography that led to diagnostic confusion by mimicking a pneumothorax.


[Comparison between modern and ancient thoughts about acupuncture treatment of migraine].
In the present paper, the authors sum up the same and different view points about acupuncture treatment of migraine in the ancient and modern clinical practice, and make a detailed explanation from three aspects: 1) the therapeutic principles, handed down from the ancient times, and still surviving in clinical practice nowadays; 2) the traditional principles recorded only in the ancient literature but given up in modern treatment; and 3) the new therapeutic principles innovated in modern clinical practice. Further comprehensive analysis reveals that the modern therapeutic principles for migraine are still relatively simple in spite of having some rather strong advantages, and some important traditional therapeutic principles have been lost unfortunately. The authors strongly recommend that the migraine, a commonly seen problem in clinic, may be managed from a new angle, i.e., solving it by puncturing acupoints of both Shaoyang and Taiyang meridians on the severer side.


Occupational Difficulties of Disaster-Affected Local Government Employees in the Long-Term Recovery Phase after the Fukushima Nuclear Accident: A Cross-Sectional Study Using Modeling Analysis.
Local government officials play a central role in post-disaster community reconstruction. However, few studies have reported on the actual difficulties during a complex disaster involving a nuclear accident. A self-rated questionnaire survey was administered to a total of 583 public employees in four municipalities around the Fukushima Daiichi Nuclear Power Station. The relationship between universal occupational factors and radiation disaster-specific factors on job satisfaction and intention to leave the job due to radiation anxiety was evaluated using structural equation modeling. The results showed that interpersonal problems (β = -0.246) and service years (β = -0.127) were related to job satisfaction, whereas radiation-specific factors were not related to job satisfaction, and only to the intention to leave work due to radiation anxiety. A sense of coherence was associated with job satisfaction (β = 0.373) and intention to leave work due to radiation anxiety (β = -0.182), and it served as a moderator of the universal occupational factors and the radiation disaster-specific factors. Therefore, it is suggested that outcomes could be improved through increased stress coping capacity by providing support for relationships and radiation risk communication to public employees during the disaster recovery period.


Academic achievement, close up work parameters, and myopia in Singapore military conscripts.
To determine the relation of refractive error to environmental factors, including close up work, in Singapore military conscripts. A cross sectional study was conducted on 429 Singapore military conscripts. Non-cycloplegic refraction and A-scan biometry were performed in both eyes. A detailed questionnaire was administered by in-person interview to obtain information about current and past near work activity, extra tuition lessons, educational experiences, and family demographics. Myopia associated with the conscript having been educated in the (gifted, special, or express) educational streams (adjusted odds ratio (OR) = 3.8, 95% confidence interval CI 2.0-7.3), and having completed pre-university education (OR=4.1, 95% CI 1.9-8.8). The reported close up work activity at age 7 years did correlate with age of onset of myopia (p<0.001). In parallel, supplemental tuition lessons in primary school has (OR=2.6, 95% CI 1.4-4.9) associated with conscript myopia. Parental myopia was positively associated with myopia (p<0.001), but this relation disappeared when adjusted for environmental factors. Current (p=0.83) and past close up work activity at age 7 years (p=0.13) did not correlate with myopia. Educational level and educational stream positively related to myopia. A relation was observed with reported close up work activity in early childhood and with tuition classes during elementary school, but not with current close up work activity. These results underscore the strong influence of environment in myopia pathogenesis but a role for close up work activity remains indeterminate.


Network meta-analysis: application and practice using R software.
The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were "gemtc" for the Bayesian approach and "netmeta" for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the "rjags" package is a common tool. "rjags" implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.


Teaching and addressing health disparities through the family medicine social and community context of care project.
By training future physicians to care for patients with backgrounds different from their own, medical schools can help reduce health disparities. To address the need for education in this area, the leaders of the Family Medicine Clerkship at the Warren Alpert Medical School of Brown University developed the Social and Community Context of Care project, required of all medical students rotating through this clerkship. Students develop a hypothetical intervention addressing a health issue seen at their preceptor site, and are assessed on their grasp of the social and contextual issues affecting that health issue in their particular community. Some interventions are actualized in later clerkships or independent study projects; one example, a health class for pregnant and parenting teens at Central Falls High School, is described here. If made a routine part of medical education, projects such as these may help medical students address the health disparities they will encounter in future practice.


[Follicular stimulating hormone receptor gene C566T mutation in premature ovarian failure].
To investigate the incidence of follicular stimulating hormone receptor (FSHR) gene C566T mutation in Chinese women with premature ovarian failure (POF) and to explore the etiologies of POF. This case-control study was carried out between 73 Chinese women with idiopathic POF (POF group) and 35 controls (control group), including 25 normal females with a regular menstrual history and 10 normal post-menopause women. DNA was extracted from the peripheral blood of patients and controls. The exon 7 of FSHR gene was amplified by PCR. PCR products were subsequently digested by the enzyme BsmI and then subjected to electrophoresis on agarose gels and stained with ethidium bromide to determine the C566T mutation. DNA samples of random sampling were further analysed by sequencing the PCR products to confirm the mutation. BsmI digestion resulting in two fragments of 51 and 27 base pairs was noted for all 73 POF patients and 35 controls. PCR sequencing confirmed that the 566 allele of FSHR gene is C, demonstrating normal FSHR allele. No FSHR gene C566T mutation is present in POF patients and controls. FSHR C566T mutation may be rare in Chinese women with POF.


Incremental direct and indirect costs of untreated vasomotor symptoms.
Most women with moderate to severe vasomotor symptoms (VMS) are untreated. This retrospective matched-cohort study aims to evaluate the healthcare resource utilization, work loss, and cost burden associated with untreated VMS. Health insurance claims (1999-2011) were used to match (1:1) women with untreated VMS with control women using propensity score. Healthcare resource utilization, work productivity loss (disability + medically related absenteeism), and associated costs were compared between cohorts. During the 12-month follow-up, women with untreated VMS (n = 252,273; mean age, 56 y) had significantly higher healthcare resource utilization than women in the control cohort: 82% higher for all-cause outpatient visits (95% CI, 81-83; P < 0.001) and 121% higher (95% CI, 118-124; P < 0.001) for VMS-related outpatient visits. Mean direct costs per patient per year were significantly higher for VMS women (direct cost difference, US$1,346; 95% CI, 1,249-1,449; P < 0.001). VMS women had 57% (95% CI, 51-63; P < 0.001) more indirect work productivity loss days than controls, corresponding to an incremental indirect cost per patient per year associated with untreated VMS of US$770 (95% CI, 726-816; P < 0.001). This study shows that untreated VMS are associated with significantly higher frequency of outpatient visits and incremental direct and indirect costs.


Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience.
Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.


Effects of Saccharomyces cerevisiae culture and Saccharomyces cerevisiae live cells on in vitro mixed ruminal microorganism fermentation.
The objective of this study was to examine the effects of a Saccharomyces cerevisiae live cell product and a S. cerevisiae culture product on the in vitro mixed ruminal microorganism fermentation of ground corn, soluble starch, alfalfa hay, and Coastal bermudagrass hay. In the presence of ground corn, neither concentration (0.35 or 0.73 g/L) of S. cerevisiae culture nor live cells had any effect on final pH, H2, CH4, propionate, or butyrate. The S. cerevisiae culture had no effect on acetate, but both concentrations of S. cerevisiae live cells decreased acetate and the acetate:propionate ratio. When soluble starch was the substrate, both concentrations of S. cerevisiae live cells and 0.73 g/L of S. cerevisiae culture decreased the acetate:propionate ratio. Although the treatment effects were not statistically significant, both concentrations of live cells and 0.73 g/L of the culture decreased lactate concentrations compared with the control incubations. When alfalfa hay served as the substrate, neither the S. cerevisiae culture nor the live cells had an effect on propionate, butyrate, or the acetate:propionate ratio. Both concentrations of S. cerevisiae culture decreased the final pH and in vitro dry matter disappearance, and the 0.73 g/L treatment decreased the amount of acetate. However, both treatments of S. cerevisiae live cells increased final pH and decreased acetate and in vitro dry matter disappearance. Neither yeast treatment had much effect on the Coastal bermudagrass hay fermentations. In general, both S. cerevisiae supplements seemed to have similar effects on the mixed ruminal microorganism fermentation.


Cell cycle specificity of apoptosis during treatment of leukaemias.
This review summarizes our observations on the mechanism of induction of apoptosis in vitro in leukaemic cell lines and in vivo in patients with leukaemia undergoing chemotherapy, in relation to the cell cycle. Multiparameter flow cytometric methods allowed us to identify apoptotic cells and position them with respect to their cell cycle phase. Several antitumor agents of different classes have been characterized in terms of the cell cycle phase specificity of induction of apoptosis. Three types of apoptosis could be distinguished in relation to the initial damage to the cell vis-a-vis cell cycle position: (1) homo-phase apoptosis where the cells underwent apoptosis during the same phase in which they were initially affected; (2) homo-cycle apoptosis, where the cells underwent apoptosis during the same cell cycle in which they were initially affected, i.e., prior to or during the first mitosis, and (3) post-mitotic apoptosis, where cells underwent apoptosis during the cell cycle(s) subsequent to that in which the cell was initially affected, most likely at the G1 or G2 checkpoints of these cycle(s). Four ranges of drug concentration can be distinguished in vitro for most drugs, where either: (1) no immediate effects; (2) cytostasis or post-mitotic apoptosis; (3) homo-cycle or homo-phase apoptosis; or (4) necrosis are observed. Analysis of cell death of blast cells from peripheral blood or bone marrow of over 250 leukaemia patients (AML, ALL, CML in blast crisis) treated with various drugs during routine chemotherapy reveals that in the case of DNA topoisomerase inhibitors (e.g., mitoxantrone, VP-16) apoptosis is often rapid (peaks at 1-2 days after drug administration) and has features of homo-phase apoptosis. In contrast, cell death observed after administration of paclitaxel (taxol) or cytarabine (cytosine arabinoside) occurs later and has features of post-mitotic apoptosis: the cells divide but die in G1 of the subsequent cycle(s).


Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity.
TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N, N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 ± 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1-1 μg s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the S1-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.


A model for occupational injury surveillance by occupational health centers.
Injuries account for more than 90% of the reported work-related health problems in the United States. However, a complete and standardized reporting system for occupational injuries does not exist in this country. This paper describes the first year's experience of a clinic-based occupational injury surveillance system involving occupational medicine clinics. During 1988, health and hazard information was collected on 14,156 work-related admissions. An analysis of these cases showed that most patients received care for minor trauma, with 78.4% of the cases classified as cuts or lacerations, sprains or strains, or contusions. Overall, 53.8% of the cases were caused by metal items, boxes, machines, or working surfaces. These preliminary results support the feasibility of conducting clinic-based occupational injury surveillance as a means of assisting employers with the control of work-related conditions.


Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis.
To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.


Rapid chlorophyll a fluorescence transients of Lemna minor leaves as indication of light and exogenous electron carriers effect on photosystem II activity.
By using saturating flash, we investigated the change in the rapid fluorescence rise when Lemna minor leaf was exposed to different light conditions and treated with exogenous electron acceptors (methyl viologen and duroquinone) and electron donor (hydroxylamine). Investigation was carried out by using combined pulse amplitude modulated fluorometer and plant efficiency analyzer system, which were employed simultaneously to provide different light conditions and to induce rapid fluorescence rise respectively. We have shown that when leaf of L. minor was exposed to different conditions of illumination, rapid fluorescence rise was greatly influenced by the electron transport functions beyond quinone A-plastoquinone reduction. This was indicated by the change in both fluorescence yield and appearance time of the different transients. When exogenous electron donor (hydroxylamine) and acceptors (methyl viologen and duroquinone) were applied in in vivo condition, we showed that rapid fluorescence rise represented a reliable indicator of PSII-PSI electron transport state and energy dissipation process.


Placental glycotype of the caviomorph rodent Lagostomus maximus and its evolution within Eutheria.
The main evolutionary milestone in the oviparity-viviparity transition is placentation. The placenta is an organ with great morphological diversity among eutherians. The expression of different glycosidic residues (Gr) in the near-term placenta constitutes its glycotype. In this study, the expression of different Gr was determined by lectin histochemistry in early, midterm, and near-term placentas of the plains viscacha (Lagostomus maximus), a caviomorph rodent with the highest poliovulatory rate and embryonic resorption rate among eutherians. Besides, a matrix with the expression of each Gr in the exchange trophoblast of viscacha and other eutherians was constructed to map and infer phylogenetic and evolutionary relationships. Between early, midterm, and near-term placentas, variations in the pattern expression of Gr were observed. The glycotype of the near-term placenta is composed of a high diversity of Gr. Reconstruction of the ancestral state for each Gr present in the near-term placenta showed a diverse scenario: some sugars were common to the species of Placentalia included in this study. In the analyzed species with synepitheliochorial and epitheliochorial placentas, no differential glycosylation patterns between them were observed. In species with invasive placentas, such as the endotheliochorial placentas of Carnivora, some common Gr were detected among them, while others were species-specific. In species with hemochorial placenta, the same Gr are shared. Particularly, in the viscacha greater differences with species of the Hominidae and even Muridae families were observed. Nevertheless, greater similarities with other caviomorph rodents were detected. Placental glycotype of each species constitutes an excellent tool to achieve phylogenetic and evolutionary inferences among eutherians.


Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19.
The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, p 0.025). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, p 0.005). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection.


TopEx: topic exploration of COVID-19 corpora - Results from the BioCreative VII Challenge Track 4.
TopEx is a natural language processing application developed to facilitate the exploration of topics and key words in a set of texts through a user interface that requires no programming or natural language processing knowledge, thus enhancing the ability of nontechnical researchers to explore and analyze textual data. The underlying algorithm groups semantically similar sentences together followed by a topic analysis on each group to identify the key topics discussed in a collection of texts. Implementation is achieved via a Python library back end and a web application front end built with React and D3.js for visualizations. TopEx has been successfully used to identify themes, topics and key words in a variety of corpora, including Coronavirus disease 2019 (COVID-19) discharge summaries and tweets. Feedback from the BioCreative VII Challenge Track 4 concludes that TopEx is a useful tool for text exploration for a variety of users and tasks. http://topex.cctr.vcu.edu.


Case Report: Dystonic Storm Following Japanese Encephalitis Virus Infection.
Dystonic storm (also called status dystonicus) is a neurological emergency characterized by sustained/intermittent involuntary generalized muscle contractions resulting in repetitive painful twisting movements and abnormal postures. It is commonly documented in patients with diagnosed primary dystonic syndromes or secondary dystonic states (i.e., patients with inborn errors of metabolism, dystonic cerebral palsy, Wilson's disease, pantothenate kinase-associated neurodegeneration, and exposure to drugs). However, viral-induced dystonic storm cases have rarely been reported. We describe the case of an 11-year-old girl from rural West Bengal (India) with a dystonic storm after Japanese encephalitis. Generalized dystonic spasms lasted for about 10-20 minutes and occurred 20-30 times/day. They were associated with extreme pain, fever, exhaustion, sweating, tachycardia, tachypnea, pupillary dilatation, arterial hypertension, and mutism and were precipitated by a full bladder and relieved somewhat during sleep. When dystonic spasms abated, she had high-grade generalized rigidity of all four limbs and fixed cervical and truncal dystonia. She was put on invasive ventilation and deep intravenous sedation with continuous midazolam infusion and other supportive measures and had a good clinical recovery. During the 12 months of follow-up, she did not have any other episode of a dystonic storm. However, axial rigidity and intermittent appendicular (upper limb) dystonic posturing were observed. The authors also have briefly discussed the differential diagnoses and treatment plans for such a neurological emergency.


Real-Time Monitoring of Curcumin Release with a Lipid-Curcumin-Loaded Silica Colloidal Crystal Film Using Optical Interferometry.
A novel efficacious strategy for real-time monitoring of the release of hydrophobic cargo curcumin (molecule model nutraceuticals) from a lipid-curcumin-loaded silica colloidal crystal (L(Cur)-SCC) film controlled by lipase was developed. Curcumin was dispersed in a proportion of a digestible lipid complex (glycerol trioleate and glycerol tristearate) to prepare a lipid-curcumin complex and then loaded into the SCC film by a capillary to prepare an L(Cur)-SCC film. Lipase-triggered degradation of the digestible lipid complex resulted in curcumin release being tracked in real-time by ordered porous layer interferometry (OPLI). The optical thickness changes (ΔOT) of the L(Cur)-SCC film depend on the mass changes of the lipid-curcumin complex due to the migration of interference fringes caused by the lipase degradation of the digestible lipid complex. Curcumin release from the L(Cur)-SCC film was characterized and analyzed in combination with an ultraviolet-visible spectrophotometer, a nanoparticle size analyzer, and an attenuated total reflection infrared spectrometer. The introduction of a soluble dietary fiber (pectin) into the L(Cur)-SCC film delayed the release rate of curcumin. Furthermore, the real-time sustained release of curcumin from the L(Cur)-SCC film in the simulated digestive fluids was tracked. This study provides an early exploration of the real-time controlled release of lipid-soluble nutraceuticals in the gastrointestinal tract.


A New Pediatric Monteggia Fracture Type 4 Variant.
Monteggia fracture-dislocations are rare and complex injuries that usually involve a fracture of the proximal ulna associated with a proximal radioulnar and radiocapitellar joint dislocations. These injuries comprise <1% of all pediatric forearm fractures. We report on a pediatric Monteggia fracture-dislocation variant that included an irreducible divergent ulnohumeral joint dislocation, an irreducible anterior radial head dislocation, and a proximal and distal radius and ulna fracture. A 6-year-old female came to our emergency room with a right elbow and forearm pain and deformity after a fall from a slide on the same day. X-rays revealed a divergent ulnohumeral joint dislocation, an anterior radiocapitellar joint dislocation, a proximal radioulnar joint dislocation, and a proximal and distal ulna and radius fracture. Closed reduction under sedation in the emergency room was not successful, with persistent ulnohumeral, ulnoradial, and radiocapitellar joint dislocations. The patient was taken to the operating room the next morning. She underwent open reduction and internal fixation of the proximal ulna fracture with a one-third tubular locking plate, and radial head dislocation open reduction. A stable reduction of the ulnohumeral joint was only possible after the fixation of the proximal ulna fracture. The most stable position for the radiocapitellar joint after its open reduction was at 70o of elbow extension and full forearm supination; the patient was casted in that position for 6 weeks. Pediatric Monteggia fracture-dislocations are rare and complex childhood fractures, and new variants of this injury can have even more complex presentations. Open reduction and stable internal fixation addressing all components of this injury will lead to an excellent outcome.


Evolution of the Xenopus piggyBac transposon family TxpB: domesticated and untamed strategies of transposon subfamilies.
A new family, termed TxpB, of DNA transposons belonging to the piggyBac superfamily was found in 3 Xenopus species (Xenopus tropicalis, Xenopus laevis, and Xenopus borealis). Two TxpB subfamilies of Kobuta and Uribo1 were found in all the 3 species, and another subfamily termed Uribo2 was found in X. tropicalis. Molecular phylogenetic analyses of their open reading frames (ORFs) revealed that TxpB transposons have been maintained for over 100 Myr. Both the Uribo1 and the Uribo2 ORFs were present as multiple copies in each genome, and some of them were framed by terminal inverted repeat sequences. In contrast, all the Kobuta ORFs were present as a single copy in each genome and exhibited high evolutionary conservation, suggesting domestication of Kobuta genes by the host. Genomic insertion polymorphisms of the Uribo1 and Uribo2 transposons (nonautonomous type) were observed in a single species of X. tropicalis, indicating recent transposition events. Transfection experiments in cell culture revealed that an expression vector construct for the intact Uribo2 ORF caused precise excision of a nonautonomous Uribo2 element from the target vector construct but that for the Kobuta ORF did not. The present results support our viewpoint that some Uribo2 members are naturally active autonomous transposons, whereas Kobuta members may be domesticated by hosts.


Cognitive impairment, frailty and rehabilitation outcome in older cardiorespiratory patients. DEC_FRAinRIAB: Study protocol.
Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are two clinical conditions often associated with functional worsening, cognitive dysfunctions, treatment non-adherence, psychological distress and poor quality of life (QoL). In addition, since patients suffering from these conditions are often older adults, the presence of frailty syndrome could worsen the clinical situation. This study protocol of a prospective multi-center clinical trial, will be conducted at two hospitals of the Istituti Clinici Scientifici Maugeri IRCCS group, from July 2020 until December 2022. CHF and COPD older patients (age ≥65) will undergo a multidisciplinary assessment at admission, discharge and at 6 months follow-up, from an inpatient rehabilitation program: disease-related clinical characteristics, functional variables, cognitive screening, treatment adherence, anxiety, depression, QoL and frailty. The estimated sample size will consist of 300 patients. The expected results are related to the possibility of an improvement in the areas of intervention after the rehabilitative program and the maintenance of these improvements over time. The assessment of clinical and functional status, cognitive impairment, treatment adherence, psychosocial characteristics, and frailty could provide more specific and useful information about the main features to be considered in the evaluation and treatment of older patients suffering from CHF and COPD undergoing a rehabilitative pathway. The study has been registered on January 28, 2022 with the ClinicalTrials.gov NCT05230927 registration number (clinicaltrials.gov/ct2/show/NCT05230927).


Controversy on the first ionization potential of PuO2 (nearly) settled by new experimental evidence.
The first ionization potential of the PuO2 molecule was for a long time considered to be 4-5 eV higher than that of UO2. This feature could hardly be explained by the most advanced "ab initio" calculations, which, on the other hand, provide satisfactory results for other actinide oxides. From recent experiments, performed with different techniques, a lower ionization potential of approximately 7 eV was measured, in better agreement with the theoretical predictions. Our recent experiments, where thermally produced ions were measured, make it possible to formulate an accurate relation between the ionization potential of PuO2 and that of PuO: I0(PuO2) = I0(PuO) + 0.42 +/- 0.005 eV. The present uncertainty of I0(PuO) leads to the final assessment, 6.2 < or = I0(PuO2) < or = 6.6 eV, whereby the upper limit is more in line with the aforementioned recent measurements. Considering the still existing uncertainties, one can conclude that these results remove major doubts on the validity of the current theoretical predictions. However, the very small ionization cross section of PuO2 by low-energy electron collisions, which led to the previous spurious assessment of the ion appearance potential, has still an unexplained cause.


Changes in rat aortic actomyosin content with maturation.
It has been reported by several investigators that the maximum active force generating ability (i.e., force/tissue cross-sectional area) of the aorta increases as the animal matures and then declines later in life. The purpose of this work was to determine if changes in the actomyosin content of the aorta occur during maturation which could contribute to the observed changes in force generating ability. The actin and myosin contents of rat thoracic aorta obtained from animals 3, 5, 7, 16 and 43 weeks of age were determined by quantitative gel electrophoresis, and were normalized with respect to tissue mass and protein and DNA contents. The results indicate that the amount of actomyosin (i.e., actin + myosin heavy chains) per tissue mass, protein and DNA increases rapidly during the first 5 weeks after birth and then remains constant. These observations suggest that the increasing actin and myosin heavy chain content of aorta observed early in life could explain in part the increasing force generating ability reported during this period, but that a loss of contractile material is not responsible for the reduction in force generating ability seen later in life.


Curated Collections for Educators: Five Key Papers about Residents as Teachers Curriculum Development.
The Accreditation Council for Graduate Medical Education (ACGME) requires residency programs to prepare residents to teach and assess medical students and other learners. In order to achieve this, many programs develop formal residents as teachers (RAT) curricula. Medical educators may seek the guidance of previously published literature during the development of RAT programs at their institutions. The authors sought to identify key articles published on the subject of RAT programs over the last 10 years. The authors utilized a formal literature search with the help of a medical librarian and identified additional articles from virtual discussions among the author group and an open call for articles on Twitter using the hashtag #MedEd. Virtual discussions occurred within an online community of practice, the Academic Life in Emergency Medicine (ALiEM) Faculty Incubator. The lead author conducted a four-round modified Delphi process among the author group in order to narrow the broad article list to five key articles on RAT programs. The authors summarize each article and provide considerations for junior faculty as well as faculty developers. Curriculum development and program evaluation should utilize established frameworks and evidence-based approaches. The papers identified by this Delphi process will help faculty use best practices when creating or revising new RAT curriculum. In addition, faculty tasked with guiding junior faculty in this process or creating faculty development programs around curriculum development will find these articles to be a great resource for building content.


Considering the Ectopic Pituitary Gland in Evaluation of the Nasopharyngeal Mass.
Extracranial pituitary ectopia is an uncommon finding characterized by all or a portion of the pituitary gland situated in an aberrant location. Often these lesions come to clinical attention only once they begin to function abnormally or increase in size significantly. We describe an incidentally noted, asymptomatic pedunculated nasopharyngeal lesion in a 13-month-old girl that may be an extracranial pituitary gland. Consideration of this rare anomaly cautioned against performing a biopsy and may have prevented inadvertent removal of functional pituitary tissue. We describe the embryologic origins of ectopic pituitary tissue, discuss the differential diagnosis for nasopharyngeal lesions in children, and emphasize physical and radiologic findings suggestive of ectopic pituitary tissue to prevent potential inadvertent removal of this rare anomaly. We report this unusual case to review embryologic origins of ectopic pituitary tissue and to alert otolaryngologists of the need to consider ectopic pituitary tissue in the diagnosis of nasopharyngeal lesions in children.


Similar grey matter abnormalities in 22q11.2DS and chronic schizophrenia: a voxel-based morphometry study.
The 22q11.2 Deletion Syndrome (22q11.2DS) is considered the most reliable biological model to study genetic vulnerability to schizophrenia. It appears useful to investigate neuroanatomical characteristics of people with 22q11.2DS compared to chronic schizophrenia and healthy controls. The sample consisted of 16 individuals with a diagnosis of schizophrenia for over 10 years (SCZ>10), 14 with a diagnosis for less than 10 years (SCZ≤10), 11 patients with 22q11.2DS with no diagnosis of psychotic disorder (DEL, n=11) and 19 healthy controls (HCs, n=19). Global intelligence (IQ) was evaluated for all subjects. Voxel-Based Morphometry (VBM) was employed to investigate potential differences between groups in grey matter volumes. VBM located the most significant difference between SCZ and HCs in the left medial frontal gyrus, where SCZ>10 group showed a significant reduction of grey matter volume; the same cluster resulted significantly decreased in DEL group compared to HCs as well. Despite the extensive grey matter abnormalities observed in 22q11.2DS, the DEL group showed the only significant differences compared to the SCZ>10 group in the right lingual gyrus volumes. Despite the small sample, our study identified a common area of grey matter loss both in idiopathic schizophrenia and 22q11.2DS.


Salternamides A-D from a Halophilic Streptomyces sp. Actinobacterium.
Salternamides A-D (1-4), the first secondary metabolites discovered from saltern-derived actinomycetes, were isolated from a halophilic Streptomyces strain isolated from a saltern on Shinui Island in the Republic of Korea. The planar structures of the salternamides, which are new members of the manumycin family, were elucidated by a combination of spectroscopic analyses. The absolute configurations of the salternamides were determined by chemical and spectroscopic methods, including the modified Mosher's method, J-based configuration analysis, and circular dichroism spectroscopy. Salternamide A (1), which is the first chlorinated compound in the manumycin family, exhibited potent cytotoxicity against a human colon cancer cell line (HCT116) and a gastric cancer cell line (SNU638) with submicromolar IC50 values. Salternamides A and D were also determined to be weak Na(+)/K(+) ATPase inhibitors.


Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer's Disease: An Illustration with Azamacrocyclic Ligands.
Targeting copper ions to either remove or redistribute them is currently viewed as a possible therapeutic strategy in the context of Alzheimer's disease (AD). Thermodynamic parameters, as for instance the copper(II) affinity of the drug candidate or the copper(II) over zinc(II) selectivity, are considered in the design of the drug candidate. In contrast, kinetic factors have been overlooked despite their probable high importance. In the present article, we use a series of azamacrocyclic ligands to demonstrate that kinetic issues must be taken into account when designing copper-targeting drug candidates in the context of AD.


[Concentration of antibiotics (cefoperazone) in human brain, brain tumor tissue and cerebrospinal fluid].
The transfer of cefoperazone (CPZ) into cerebrospinal fluid (CSF), brain or brain tumor tissue was studied in 13 cases with brain tumor, chronic subdural hematoma and benign intracranial hypertension in 1982. The peak values of CPZ in serum came up immediately after its rapid intravenous administration and then decreased exponentially. The concentration of CPZ in CSF started to increase with a long delay of about 60 min. The average peak level in CSF remained 21.6 micrograms/ml and corresponded to 10.3% of the peak level in serum. The best transfer of chloramphenicol into CSF has been reported, while that of CPZ would be one of the next. The CPZ levels in CSF showed a slower decay than in serum. The concentration of CPZ in brain reached the peak level in less than 30 min and the average peak level was 36.5 micrograms/g cerebral tissue. The brain to blood rate of the CPZ concentration was 11.1%. The CPZ levels in the brain showed a rapid decrease like the transition of antibiotic levels in serum. The antibiotic levels in brain tumors were divided into two groups. The one showed sharp peak about one tenth of the values in serum. The other was of a slowly increasing type.


Vitamin D receptor activation raises soluble thrombomodulin levels in chronic kidney disease patients: a double blind, randomized trial.
Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix that regulates the haemostasis and the endothelial response to inflammation. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates TM, but the effect of this intervention on soluble TM has never been tested in chronic kidney disease (CKD) patients. We performed a post hoc analysis of a 12 weeks double blind, randomized, placebo-controlled trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow-mediated vasodilatation (FMD) in the forearm (ClinicalTrials.gov identifier: NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n = 44; placebo n = 44] that took part into this trial. Soluble TM at baseline was inversely related to the glomerular filtration rate (r = -0.65, P < 0.001) and to FMD (Spearman's ρ = -0.29, P = 0.01). Alongside the expected effects on bone mineral biomarkers, PCT produced a consistent rise (P = 0.005) in TM levels, from a median value of 8446.0 pg/mL [interquartile range (IQR): 6227.8-10 910.8 pg/mL] to 9127.5 pg/mL (6393.0-11 287.3 pg/mL) while placebo had no effect (between-groups difference P = 0.008). TM levels re-approached baseline values 2 weeks after stopping PCT. TM changes across the trial paralleled simultaneous changes in FMD. VDR activation by PCT raises TM levels and FMD and such effects are rapidly reversible after stopping the treatment. The TM rise induced by PCT is a possible mechanism whereby improvement in endothelial function by VDR activation may favourably impact upon vascular health in CKD patients.


Neurons in rostral VLM are inhibited by chemical stimulation of caudal VLM in rats.
Recent evidence suggests that neurons in the caudal ventrolateral medulla (CVLM) exert a tonic inhibition on the neurons in the rostral ventrolateral medulla (RVLM) that are essential for the maintenance of arterial pressure (AP). To test the hypothesis that selective activation of cell bodies in the CVLM can inhibit the discharge of neurons in the RVLM, activity from 88 neurons in the RVLM was recorded extracellularly while 2-30 nl sodium glutamate (Glu; 0.15 M) were microinjected into depressor sites of the CVLM of urethan-anesthetized male Wistar rats. Results obtained from spontaneously breathing and artificially ventilated rats were essentially similar and are presented together. Twenty-five neurons were characterized as cardiovascular because they were inhibited by baroreceptor activation and showed rhythmicity of their spontaneous activity in synchrony with the cardiac cycle. Activation of cell bodies in the CVLM inhibited the firing rate of 23 of these cardiovascular neurons and excited 2. The remaining 63 neurons could not be considered cardiovascular because they either were not barosensitive or lacked cardiac cycle-related rhythmicity. Injection of Glu into the CVLM inhibited 26 of these neurons, excited 22, and had no effect on 15. These results provide direct evidence for the existence of an inhibitory pathway from neurons located in the CVLM to cardiovascular neurons in the RVLM.


Translocation of Human β Defensin Type 3 through a Neutrally Charged Lipid Membrane: A Free Energy Study.
Human β defensin type 3 (hBD-3) is a cationic (+11 charged) antimicrobial peptide. It has three pairs of intramolecular disulfide bonds which can break under reducing conditions to convert hBD-3 into the linear analog form. hBD-3 can disrupt both Gram-positive and Gram-negative cell membranes, and even the mammalian cell membrane at high concentrations. However, the structural basis for the membrane-disrupting function of hBD-3 is still unknown. In order to understand the interaction mechanism of hBD-3 with a neutrally charged lipid membrane, explicit solvent and lipid umbrella-sampling simulations were performed using the NAMD program on the hBD-3 wild-type and the linear analog, in both the monomer and dimer forms. During the insertion and translocation process, most of the protein structure changes take place near the membrane-solvent interface, while the membrane interior appears to stabilize and rigidify the native-like hBD-3 structure. An energy barrier of 20 kcal/mol (domain unit) should be overcome by hBD-3 dimer in wild-type to cross the POPC bilayer but only 13 kcal/mol (domain unit) to insert into the bilayer center, and 20 kcal/mol for hBD-3 monomers to insert into the membrane center. Significant reorientation of lipids around hBD-3 inside the membranes was observed, which suggests a toroidal model for the membrane disruption process.


Plant-associated microbiota as a source of antagonistic bacteria against the phytopathogen Erwinia amylovora.
Control of bacterial plant diseases is a major concern, as they affect economically important species and spread easily, such as the case of fire blight of rosaceous caused by Erwinia amylovora. In the search for alternatives to the use of agrochemicals and antibiotics, this work presents a screening of natural bacterial antagonists of this relevant and devastating phytopathogen. We recovered bacterial isolates from different plant tissues and geographical origins and then selected those with the strongest ability to reduce fire blight symptoms ex vivo and remarkable in vitro antagonistic activity against E. amylovora. None of them elicited a hypersensitivity reaction in tobacco leaves, most produced several hydrolytic enzymes and presented other biocontrol and/or plant growth-promoting activities, such as siderophore production and phosphate solubilization. These isolates, considered as biocontrol candidates, were identified by 16S rRNA sequencing as Pseudomonas rhizosphaerae, Curtobacterium flaccumfaciens, Enterobacter cancerogenus, Pseudomonas azotoformans, Rosenbergiella epipactidis and Serratia plymuthica. This is the first time that the last five bacterial species are reported to have biocontrol potential against E. amylovora.


The diagnostic role of cervico-vaginal fluid interleukins-1α in endometriosis: A case-control study.
Endometriosis is a chronic and progressive gynecological disorder and is manifest by dysmenorrhea and a major cause of infertility and chronic pelvic pain. The study was designed to compare the value of cervico-vaginal fluid of interleukin-1α (IL-1α) in patients with and without endometriosis. Fifty women were assessed in this case control study. The case group included 25 patients with endometriosis. The control group included 25 women without any evidence of endometriosis or any other genital disease. Endometriosis was confirmed by laparoscopy and histopathological examination. Cervico-vaginal fluid samples were obtained from patients during the follicular phase and preup surgery to assess the levels of IL-1α in cervico-vaginal fluid. The level of IL-1α was assessed using commercially available Avi Bionhuman Enzyme-Linked Immunosorbent Assay kits (FIN-01720, Vantaa, Finland) for IL-1α. Receiver-operator curve analysis was used to estimate the power of IL-1α to distinguish subjects with endometriosis from controls. The cervico-vaginal fluid level of IL-1α in cases was 210.44 ± 40.11 pg/mL and in controls was 54.28 ± 25.73 pg/mL, the differences between two groups was statistically significant (P < 0.0001). The cut-off point for cervico-vaginal fluid IL-1 for endometriosis was 105 pg/mL, with a sensitivity of 100% (95% confidence interval [CI]: 86.2-100), and specificity of 100% (95% CI: 86.2-100). Results show a significant increase in the cervico-vaginal fluid levels of IL-1α, in women with endometriosis, that it can be a useful marker in the diagnosis of endometriosis.


Arthroscopic Knotless, Tensionable All-Suture Anchor Bankart Repair.
Surgical management for glenohumeral instability has advanced to provide stronger fixation and to be less invasive. Arthroscopic suture anchor repair has been the gold standard for isolated capsulolabral tears over the years. Despite the ability of the solid suture anchors to handle physiologic load, they can present challenges such as chondral damage due to anchor size and imperfect angulation, osteolysis, anchor breakage, revision drilling, difficulty of revision surgery with accompanied bone loss, and compromised postoperative magnetic resonance imaging quality. Recently, knotless all-suture anchors have been introduced as a technique to overcome these challenges. These anchors lack a rigid component and can be placed in a tunnel of smaller diameter, thereby allowing for maintenance of glenoid bone stock. The purpose of this Technical Note is to describe our preferred surgical technique with a minimally invasive approach for the fixation of capsulolabral tears using a knotless all-suture anchor construct.


Dynamics and pattern formation of ring dark solitons in a two-dimensional binary Bose-Einstein condensate with tunable interactions.
We investigate the dynamics and pattern formation of two ring dark solitons in a two-dimensional binary Bose-Einstein condensate with tunable intercomponent interaction via numerical simulation of the time-dependent Gross-Pitaevskii equation. Both the black and gray ring dark solitons are considered for cases where the modulation frequency of the intercomponent interaction is resonant or nonresonant with the one of the trapping potential. Our results show that in the presence of periodic modulation of the intercomponent interaction not only are the lifetimes of the ring dark solitons largely extended but also their decaying dynamics are dramatically affected. Before snaking instability sets in, new ring dark solitons are formed, and both the numbers and depths of the ring dark solitons exhibit collective oscillations. With the development of instability, the system exhibits different decaying processes, and a variety of decay profiles, such as vortex necklace, distorted octagon, vortex-antivortex ring, and cross, are formed, showing a strong dependence on the modulation frequency of the intercomponent interaction and the initial depth of the ring dark soliton.


Transurethral fluorescence cystoscopy guidance for total resection of bladder tumor.
The purpose of this work is to investigate the total resection of bladder tumor under transurethral fluorescence cystoscopy. Nineteen patients with bladder tumor, from which we resected a total of 26 tumors, including 16 single tumors with diameters of 0.5~2 cm, were enrolled in the study. All tumors were located in the posterior wall or neck of the bladder. For the surgery, the size and location of tumors in the bladder were observed by fluorescence cystoscopy. Then, plasma electrocision was used to cut the full-thickness of the bladder to the fat outside of the bladder along the near-end of the tumor, then along the left and right side of bladder (to the far-end), and the full-thickness of the tumor was resected. Finally, the far-end tumor was removed and the full-thickness of the bladder at the bottom was completely resected. All operations were completed successfully within 10-40 min. There was little bleeding during surgery and no secondary bleeding after surgery. Tumor staging found 17 patients at T1 stage (20 tumors) and 2 patients at T2 stage (6 tumors). Patients were followed up for 6~12 months without any recurrence. We show here that total resection of bladder tumor can be accomplished under transurethral fluorescence cystoscopy and preventative resection can be conducted on the suspicious bladder wall with precision to eliminate tumor residue that promotes recurrence.


SUMOylation Pattern Predicts Prognosis and Indicates Tumor Microenvironment Infiltration Characterization in Bladder Cancer.
SUMOylation is an important component of post-translational protein modifications (PTMs), and bladder cancer (BCa) is the ninth most common cancer around the world. But the comprehensive role of SUMOylation in shaping tumor microenvironment (TME) and influencing tumor clinicopathological features and also the prognosis of patients remains unclear. Using the data downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we comprehensively evaluated the SUMOylation patterns of 570 bladder cancer samples, and systematically correlated these SUMOylation patterns with TME immune cell infiltrating characteristics. The SUMO score was constructed to quantify SUMOylation patterns of individuals using principal component analysis (PCA) algorithms. Two distinct SUMOylation patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different SUMOylation patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system named SUMO score to quantify the SUMOylation pattern of individuals with BCa, which was discovered to be tightly connected with tumor clinicopathological characteristics and could predict the prognosis of patients with BCa. Moreover, SUMO score was a considerable predictive indicator for the survival outcome independent of tumor mutation burden (TMB) and low SUMO score was related to better response to immunotherapy using PD-1 blockade. We also found that there existed a significant relationship between sensitivity to commonly used chemotherapy drugs and SUMO score. Finally, a nomograph based on five features, namely, SUMO score, age, gender, T category, and M category was constructed to predict the survival probability of patients with BCa in 1, 3, and 5 years, respectively. Our work demonstrated and overviewed the complicated regulation mechanisms of SUMOylation in bladder cancer, and better understanding and evaluating SUMOylation patterns could be helpful in guiding clinical therapeutic strategy and improving the prognosis of patients with BCa.


The change of life, the sorrow of life: menopause, bad blood and cancer among Italian-Australian working class women.
This paper explores the discourse of menopause, health and illness among 20 middle aged Italo-Australian working class women living in Melbourne. Using the methods of interpretative anthropology and the perspectives of critical feminist theory, I argue that women's discourse about health and illness is one way in which they express feelings of loss over the fertility of their youth, ambivalences about their lives in Australia, and grief over a life left behind in Italy. These losses are experienced physically and expressed metaphorically through conditions of bad blood and nerves and are perceived to contribute to their vulnerability to a range of diseases including cancer. For these women, the change of life is experienced as the end of life and their fear of cancer is representative of their fears of social and physical death. Cancer is also seen to be a disease more common in Australia and is used as a metaphor for expressing anxieties relating to feelings of placelessness, of being disconnected from one's roots, and anxieties about becoming old and dying far from "home."


[Guidelines for the treatment of anemia in chronic renal failure].
Evaluation of anemia: Before beginning epoetin treatment, it is essential to evaluate the level of anemia (Hb < 11-12g/dL) by the following measurements: -Hb concentration -Red blood cell indices (MCV, MCH, MCHC) -Reticulocyte count -Iron stores and availability -C-reactive protein (CRP) Target for anemia treatment: The minimum target Hb concentration to be attained is 11 g/dL. The upper limit is established individually on a clinical basis. Pending further data, it is advisable to maintain and not exceed 12 g/dL for patients with cardiovascular disease, diabetes, and graft access. Use of iron: At the start of epoetin treatment, 150 mg of iron are needed for every expected increase of 1 g/dL of Hb. It is important to achieve and maintain levels of TSAT > 20%, serum ferritin 100 mcg/L and hypochromic red cells > 6% both before initiating epoetin treatment and during its administration. TSAT levels should not persistently exceed > 50% and serum ferritin > 500 mcg/L. When administering oral iron the dose should be at least 200 mg/die elemental iron; on the other hand, when the intravenous route is used, the dose should be 30-60 mg/IV dose in the form of low molecular weight salts (iron sodium gluconate) while the higher doses should be reserved for patients with transferring levels > 170 mg/dL. Administration of epoetin: The dosage of epoetin is individual with more than tenfold variability among individuals and all aiming at the same target Hb concentration. There are no clinical parameters entirely capable of predicting the necessary dosage. Therapeutic range is very wide, without any toxic effects for clinical use up to 100.000 IU/week. The target Hb concentration is reached in most patients with mild anaemia after 2 months' treatment with 4.000-10.000 epoetin (20-50 mcg darbepoetin alpha) per week. The HB concentration, along with the reticulocyte count, must be checked weekly following initiation and monthly during maintenance. Patients with a stable dose-response during conservative therapy may require less frequent monitoring (every 2-3 months). Inadequate response to epoetin treatment If any resistance is encountered, after excluding all the acute and chronic conditions of inadequate response, the reticulocyte count (severe reduction in the presence of anti erythropoietin antibodies) and the erythropoietin dosage should be measured. The target Hb concentration 11-12 g/dL is maintained in 90-95% of the patients by administering 1.000-30.000 IU of epoetin (5-150 mcg darbepoetin alpha) per week in the presence of adequate reserves of iron. Higher dosages define a state of resistance. Diagnosis of pure red cell (PRCA) from anti-erythropoietin antibodies is confirmed by bone marrow examination (almost total loss of erythroblasts). If antierythropoietin antibodies are present or there is a well founded suspicion of PRCA, the administration of epoetin and other similar treatment should be avoided. Side effects of epoetin treatment: The treatment of anaemia with epoetin does not hasten the progression of CRF. Blood pressure is to be checked regularly during initiation of epoetin and the treatment should be discontinued in cases of refractory hypertension or hypertensive encephalopathy. There should be increased surveillance of graft access, especially in those patients who risk vascular depletion. In general, heparin requirements do not increase but it may be advisable to evaluate a dose increase. PRCA from anti-erythropoietin antibodies has been detected with an incidence ranging from 0.12 to 1.1 cases/every 10 thousand patients treated.


Low-dose deoxycoformycin in lymphoid malignancy.
Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.


[A multi-parameter resting-state functional magnetic resonance imaging study of brain intrinsic activity in attention deficit hyperactivity disorder children].
A great number of studies have demonstrated functional abnormalities in children with attention-deficit/hyperactivity disorder (ADHD), although conflicting results have also been reported. And few studies analyzed homotopic functional connectivity between hemispheres. In this study, resting-state functional magnetic resonance imaging (MRI) data were recorded from 45 medication-naïve ADHD children and 26 healthy controls. The regional homogeneity (ReHo), degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were compared between the two groups to depict the intrinsic brain activities. We found that ADHD children exhibited significantly lower ReHo and DC values in the right middle frontal gyrus and the two values correlated with each other; moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD children, which was negatively related with anxiety scores of Conners' Parent Rating Scale (CPRS-R) and positively related with completed categories of Wisconsin Card Sorting Test (WCST). Our results might suggest that less spontaneous neuronal activities of the right middle frontal gyrus and the bilateral occipital lobes in ADHD children.


Report on the international Primary Neurosurgical Life Support course in the eighth Asian Congress of Neurological Surgeons in Kuala Lumpur, Malaysia.
On November 22, 2010, a simulation-based hands-on education course for medical staff in the neurosurgical fields was held in 8(th) Asian Congress of Neurological Surgeons (ACNS) in Kuala Lumpur, Malaysia. The present education course called Primary Neurosurgical Life Support (PNLS) course had been started by the Japan Society of Neurosurgical Emergency since 2008. This report summarizes the international version of PNLS course in 8(th) ACNS.


Comparison between civilian burns and combat burns from Operation Iraqi Freedom and Operation Enduring Freedom.
To assess outcome differences between locally burned civilians and military personnel burned in a distant combat zone treated in the same facility. The United States Army Institute of Surgical Research (USAISR) Burn Center serves as a referral center for civilians and is the sole center for significant burns in military personnel. We made the hypothesis that outcomes for military personnel burned in the current conflict in Iraq and Afghanistan would be poorer because of delays to definitive treatment, other associated injury, and distance of evacuation. We reviewed the civilian and military records of patients treated at the USAISR from the outset of hostilities in Iraq in April 2003 to May 2005. Demographics, injury data, mortality, and clinical outcomes were compared. : We cared for 751 patients during this time period, 273 of whom were military (36%). Military injuries occurred in a younger population (41 +/- 19 vs. 26 +/- 7 years for civilian and military respectively, P < 0.0001) with a longer time from injury to burn center arrival (1 +/- 5 days vs. 6 +/- 5, P < 0.0001), a higher Injury Severity Score (ISS 5 +/- 8 vs. 9 +/- 11, P < 0.0001), and a higher incidence of inhalation injury (8% vs. 13%, P = 0.024). Total burn size did not differ. Mortality was 7.1% in the civilian and 3.8% in the military group (P = 0.076). When civilians outside the age range of the military cohort were excluded, civilian mortality was 5.0%, which did not differ from the military group (P = 0.57). Total body surface area (TBSA) burned, age > or =40 years, presence of inhalation injury, and ventilator days were found to be important predictors of mortality by stepwise regression, and were used in a final predictive model with the area under receiver operator characteristic curve of 0.97 for both populations considered together. No significant effect of either group was identified during development. Mortality does not differ between civilians evacuated locally and military personnel injured in distant austere environments treated at the same center.


Integration of a multi-omics stem cell differentiation dataset using a dynamical model.
Stem cell differentiation is a highly dynamic process involving pervasive changes in gene expression. The large majority of existing studies has characterized differentiation at the level of individual molecular profiles, such as the transcriptome or the proteome. To obtain a more comprehensive view, we measured protein, mRNA and microRNA abundance during retinoic acid-driven differentiation of mouse embryonic stem cells. We found that mRNA and protein abundance are typically only weakly correlated across time. To understand this finding, we developed a hierarchical dynamical model that allowed us to integrate all data sets. This model was able to explain mRNA-protein discordance for most genes and identified instances of potential microRNA-mediated regulation. Overexpression or depletion of microRNAs identified by the model, followed by RNA sequencing and protein quantification, were used to follow up on the predictions of the model. Overall, our study shows how multi-omics integration by a dynamical model could be used to nominate candidate regulators.


Reductions in blood loss with use of a bipolar sealer for hemostasis in primary total knee arthroplasty.
Fifty primary total knee arthroplasties were performed in a prospective, randomized study comparing the use of a bipolar sealer device versus conventional electrocautery as the method of hemostasis. Both cohorts were evaluated for intraoperative blood loss, transfusion rate, postoperative drainage, hemoglobin levels, and Knee Society scores. A significant reduction in postoperative and total blood loss was found (p = 0.05 and p = 0.02, respectively), as well as an absence of tissue charring and smoke production in the bipolar sealer group. No difference in knee scores was found between both cohorts. These results suggest that use of this bipolar sealing device is at least as effective as standard cautery devices and can reduce blood loss, tissue damage, and smoke production in total knee arthroplasties without affecting the results.


Optimization of source and detector configurations based on Cramer-Rao lower bound analysis.
Optimization of source and detector (SD) arrangements in a diffuse optical tomography system is helpful for improving measurements' sensitivity to localized changes in imaging domain and enhancing the capacity of noise resistance. We introduced a rigorous and computationally efficient methodology and adapt it into the diffuse optics field to realize the optimizations of SD arrangements. Our method is based on Cramer-Rao lower bound analysis, which combines the diffusion-forward model and a noise model together. This method can be used to investigate the performance of the SD arrangements through quantitative estimations of lower bounds of the standard variances of the reconstructed perturbation depths and values. More importantly, it provides direct estimations of parameters without solving the inverse problem. Simulations are conducted in the reflection geometry to validate the effectiveness of the method on selections of the optimized SD sets, with a fixed number of sources and detectors, from an SD group on a planar probe surface. The impacts of different noise levels and target perturbation depths are considered in the simulations. It is demonstrated that the SD sets selected by this method afford better reconstructed images. This methodology can be adapted to other probe surfaces and other imaging geometries.


Ursodeoxycholic acid, chenodeoxycholic acid, and 7-ketolithocholic acid are primary bile acids of the guinea pig.
Guinea pig gallbladder bile contains chenodeoxycholic acid (62 +/- 5%), ursodeoxycholic acid (8 +/- 5%), and 7-ketolithocholic acid (30 +/- 5%). All three bile acids became labeled to the same specific activity within 30 min after [3H]cholesterol was injected into bile fistula guinea pigs. When a mixture of [3H]ursodeoxycholic acid and [14C]chenodeoxycholic acid was infused into another bile fistula guinea pig, little 3H could be detected in either chenodeoxycholic acid or 7-ketolithocholic acid. But, 14C was efficiently incorporated into ursodeoxycholic and 7-ketolithocholic acids. Monohydroxylated bile acids make up 51% and ursodeoxycholic acid 38% of fecal bile acids. After 3 weeks of antibiotic therapy, lithocholic acid was reduced to 6% of the total, but ursodeoxycholic acid (5-11%) and 7-ketolithocholic (15-21%) acid persisted in bile. Lathosterol constituted 19% of skin sterols and was detected in the feces of an antibiotic-fed animal. After one bile fistula guinea pig suffered a partial biliary obstruction, ursodeoxycholic and 7-ketolithocholic acids increased to 46% and 22% of total bile acids, respectively. These results demonstrate that chenodeoxycholic acid, ursodeoxycholic acid, and 7-ketolithocholic acid can all be made in the liver of the guinea pig.


A CFD Study on Heat Transfer Performance of SiO2-TiO2 Nanofluids under Turbulent Flow.
A CFD model was performed with commercial software through the adoption of the finite volume method and a SIMPLE algorithm. SiO2-P25 particles were added to water/ethylene glycol as a base fluid. The result is considered a new hybrid nanofluid (HN) for investigating heat transfer (HT). The volume concentrations were 0.5, 1.0, and 1.5%. The Reynolds number was in the range of 5000-17,000. The heat flux (HF) was 7955 W/m2, and the wall temperature was 340.15 K. The numerical experiments were performed strictly following the rules that one should follow in HT experiments. This is important because many studies related to nanofluid HT overlook these details. The empirical correlations that contain the friction factor perform better with higher Reynolds numbers than the correlations based only on Reynolds and Prandtl numbers. When temperature differences are moderate, researchers may consider using constant properties to lower computational costs, as they may give results that are similar to temperature-dependent ones. Compared with previous research, our simulation results are in agreement with the experiments in real time.


Failure of suture material at suture anchor eyelets.
In the repair of soft tissue to bone using suture anchors, failure of the suture material can occur at the anchor eyelet. This study examines the load strength at which suture material fails with different metallic suture anchor eyelets. Biomechanical study. Suture material (Ethibond No. 2, Ethicon, Norderstedt, Germany) was pulled out from 22 metallic suture anchor models at 60 mm/min, and tensile load at failure and failure mode were recorded. Tests were performed either by simultaneous pulling on 2 suture limbs in 3 different directions (straight, at 45 degrees, and at 45 degrees rotated by 90 degrees to the suture anchor axis) or by pulling on 1 suture limb while measuring the resulting force on the second limb. All tests were performed until suture failure. Pulling was performed in single tests on an Instron materials testing machine (High Wycombe, UK), with the anchors held by a vise. In all cases, the suture failed at the anchor eyelet. Failure load at straight loading ranged from 116 +/- 5 N to 226 +/- 5 N and from 69 +/- 5 N to 193 +/- 7 N when loaded at an angle of 45 degrees. The best results were found with the Statak 5.2-mm (Zimmer, Warsaw, IN): 177 N; Corkscrew 6.5-mm anchor (Arthrex, Naples, FL): 174 N; and PeBA 4.0-mm anchor (OBL Orthopaedic Biosystems, Scottsdale, AZ): 169 N. With each eyelet, sutures failed preferentially in 1 direction, depending on the presence of sharp edges. Suture material can be cut at suture anchor eyelets. Failure load depends on sharp edges on the eyelet and occurs at forces up to 73% below the breaking strength of the suture material on a smooth hook. Anchors with suture-protecting channels are particularly sensitive to the orientation in which the sutures are loaded.


The gender-related variability in the pharmacokinetics and antiplasmodial activity of naphthoquine in rodents.
Naphthoquine (NQ) is a suitable partner anti-malarial for the artemisinin-based combination therapy (ACT), which is recommended to be taken orally as a single-dose regimen. The metabolism of NQ was mainly mediated by CYP2D6, which is well-known to show gender-specific differences in its expression. In spite of its clinical use, there is limited information on the pharmacokinetics of NQ, and no data are available for females. In this study, the effect of gender on the pharmacokinetics and antiplasmodial efficacy of NQ in rodents was evaluated. The underlying factors leading to the potential gender difference, i.e., plasma protein binding and metabolic clearance, were also evaluated. The pharmacokinetic profiles of NQ were investigated in healthy male or female rats after a single oral administration of NQ. The antiplasmodial efficacy of NQ was studied in male or female mice infected with Plasmodium yoelii. The recrudescence and survival time of infected mice were also recorded after drug treatment. Plasma protein binding of NQ was determined in pooled plasma collected from male or female mice, rat or human. In vitro metabolism experiments were performed in the liver microsomes of male or female mice, rat or human. The results showed that the gender of rats did not affect NQ exposure (AUC0-t and Cmax) significantly (P > 0.05). However, a significant (P < 0.05) longer t1/2 was found for NQ in male rats (192.1 ± 47.7), compared with female rats (143.9 ± 27.1). Slightly higher but not significant (P > 0.05) antiplasmodial activity was found for NQ in male mice (ED90, 1.10 mg/kg) infected with P. yoelii, compared with female mice (ED90, 1.67 mg/kg). The binding rates of NQ to plasma protein were similar in males and females. There was no metabolic difference for NQ in male and female mice, rat or human liver microsomes. These results indicated that the pharmacokinetic profiles of NQ were similar between male and female rats, except for a longer t1/2 in male rats. The difference was not associated with plasma protein binding or hepatic metabolic clearance. Equivalent antiplasmodial activity was found for NQ in male and female mice infected with P. yoelii. This study will be helpful for the rational design of clinical trials for NQ.


[The dissertation as a final product of a specialty in medicine].
Submitting a written report of a research proyect, also known as dissertation (or thesis), is one of the requirements established by academic institutions for the student to achieve the degree of specialist in medicine. Preparing the dissertation is not only an academic challenge for postgraduate students and professors; it is also a logistical challenge. Highlighting that effort and the dissertation itself will result in a better attention for the beneficiaries of the Instituto Mexicano del Seguro Social.


Metabolite profiling and bioactivity of rice koji fermented by Aspergillus strains.
In this study, the metabolite profiles of three Aspergillus strains during rice koji fermentation were compared. In the partial least squares discriminant analysis-based gas chromatography-mass spectrometry data sets, the metabolite patterns of A. oryzae (KCCM 60345) were clearly distinguished from A. kawachii (KCCM 60552) and only marginal differences were observed for A. oryzae (KCCM 60551) fermentation. In the 2 days fermentation samples, the overall metabolite levels of A. oryzae (KCCM 60345) were similar to the A. oryzae (KCCM 60551) levels and lower than the A. kawachii (KCCM 60552) levels. In addition, we identified discriminators that were mainly contributing tyrosinase inhibition (kojic acid) and antioxidant activities (pyranonigrin A) in A. oryzae (KCCM 60345) and A. kawachii (KCCM 60552) inoculated rice koji, respectively. In this study, we demonstrated that the optimal inoculant Aspergillus strains and fermentation time for functional rice koji could be determined through a metabolomics approach with bioactivity correlations.


[DNA repair and carcinogenesis].
Recent research support the idea that DNA damage is the initial event in the process of carcinogenesis. Involvement of DNA repair in the fixation of DNA damage leading to cancer has been suggested by the presence of several cancer-prone hereditary diseases associated with DNA repair deficiency. Among them, xeroderma pigmentosum has been most extensively investigated and the "SOS response" hypothesis, originally implied to the mechanism of mutagenesis in bacteria, appears to be an attractive hypothesis for the understanding of the cancer-proneness in xeroderma pigmentosum. The DNA repair of ionizing radiation damage, however, has not been clearly demonstrated in association with the process of radiation carcinogenesis, and further studies will be needed to understand the mechanisms of radiation carcinogenesis and the involvement of DNA repair in it.


The Effects of Aloe vera Cream on the Expression of CD4+ and CD8+ Lymphocytes in Skin Wound Healing.
The aim of this study is to explore the effect of topical application of Aloe vera on skin wound healing. Thirty-six male Sprague-Dawley rats weighing 150-200 grams were divided into four groups. All groups were anesthetized, shaved, and exposed to round full-thickness punch biopsy on the back: group I (control); group II (treated with 1% Aloe vera cream); group III (treated with 2% Aloe vera cream); and group IV (treated with madecassol®). The treatments were given once a day. Macroscopic and microscopic examination were observed at 5, 10, and 15 days after skin biopsy. Skin specimens were prepared for histopathological study using H&E stain and IHC stain against CD4+ and CD8+ lymphocytes. All the data were analyzed using SPSS16. The result showed that topical application of 1% and 2% Aloe vera cream significantly reduced the percentage of the wound, leucocytes infiltration, angiogenesis, and expression of CD8+ lymphocytes and increased the epidermal thickness and the expression of CD4+ lymphocytes (p ≤ 0,05). There was no significant difference in the number of fibroblasts in all groups. Topical application of 1% and 2% Aloe vera cream has wound healing potential via their ability to increase the ratio of CD4+/CD8+ lymphocytes in the wound area.


High unmet-need infectious disease opportunities.
Despite advances in pharmaceutical science, considerable unmet medical needs exist in the field of anti-infective therapies. While pharmaceutical companies have focused research efforts on a few selected areas of the field, new microbial diseases have steadily increased in prevalence. Three emerging areas in the field of anti-infectives now represent large commercial opportunities: Gram-negative infections, community-acquired methicillin-resistant Staphylococcus aureus, and Clostridium difficile-associated diarrhea. Dedication and extensive investment by pharmaceutical companies is required to battle against these emerging and deadly microbial infections.


Physiological and oxidative stress responses of Solanum lycopersicum (L.) (tomato) when exposed to different chemical pesticides.
Pesticide overuse can have negative effects on developmental processes of non-target host plants. By increasing reactive oxygen species (ROS) levels, pesticides negatively affect cellular metabolism, biochemistry and physiological machinery of plants. Considering these problems, the current study was planned to assess the effect of three different groups of pesticides, namely diazinon (DIZN), imidacloprid (IMID) and mancozeb (MNZB) on Solanum lycopersicum L. (tomato). In general, pesticides resulted in a progressive decrease in physiological and biometric parameters of S. lycopersicum (L.), which varies significantly among concentrations and species of pesticides. Among them, 200 μgMNZB mL-1 had the most severe negative impact and reduced germination rate, root biomass, chl a, chl b, total chlorophyll and carotenoids by 62, 87, 90, 88, 92 and 90%, respectively. In addition, higher doses of pesticides greatly reduced the flowering, fruit attributes and lycopene content. Furthermore, plants exposed to 200 μgDIZN mL-1 showed a progressive drop in root cell viability (54% decrease), total soluble sugar (TSS) (64% decrease) and total soluble protein (TSP) (67% decrease) content. Data analysis indicated that greater doses of pesticides dramatically raised ROS levels and induced membrane damage through production of thiobarbituric acid reactive substances (TBARS), as well as increased cell injury. To deal with pesticide-induced oxidative stress, plants subjected to greater pesticide dosages, showed a substantial increase in antioxidant levels. For instance, ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and guaiacol peroxidase (GPX) were maximally increased by 48, 93, 71, 52 and 94%, respectively following 200 μgMNZB mL-1 soil exposures. Additionally, under a confocal laser scanning microscope (CLSM), pesticide exposed S. lycopersicum (L.) roots stained with 2',7'-dichlorodihydrofluorescein diacetate (2'7'-DCF) and 3,3'-diaminobenzidine, exhibited an increased ROS production in a concentration-dependent manner. Further, elevated pesticide concentrations resulted in alterations in mitochondrial membrane potential (ΔΨ m) and cellular death in roots, as evidenced by increased Rhodamine 123 (Rhd 123) and Evan's blue fluorescence, respectively. These findings clearly showed that applying pesticides in excess of permissible amounts might induce oxidative stress and cause oxidative damage in non-target host plants. Overall, the current study indicates that a thorough and secure method be used before selecting pesticides for increasing production of agronomically important vegetable crops in various agro-climatic zones.