Synthesis, characterization, thermal properties, antimicrobial evaluation, ADMET study, and molecular docking simulation of new mono Cu (II) and Zn (II) complexes with 2-oxoindole derivatives.
One of the interesting research fields is developing and assessing novel metal-containing medications. A new isatin-3-thiosemicarbazone derivative 4 was synthesized by two different methods based on hydrazone derivatives 2 and 3. Additionally, the chelation of thiosemicarbazone with copper (II) and zinc (II) forms a monobasic tridentate (ONS) complex with two five-member rings and a tetrahedral geometry structure. The structure of synthesized complexes was characterized using elemental analysis, FT-IR, mass spectra, and 1H/13C NMR. Thermogravimetric analysis revealed the upgrading of the thermal stability of metal complexes compared to their thiosemicarbazone ligand. The stoichiometric ratio of the coordination confirmed the formation of 1:1 (M: L) stoichiometry. In vitro antimicrobial activity was screened against two gram-positive, two gram-negative, and one fungal strain. Both ligand 4 and Zn complex 6 displayed high antimicrobial activity compared with copper complex 5 based on the zone of inhibition. Further, MIC and MBC were determined for both zinc and ligand. The zinc complex 6 displayed excellent antimicrobial activity with (MIC = 3.9-27.77 μg/mL) against bacterial strains and (MIC = 7.81 μg/mL) against C. albicans, as well as exhibited MBC values ranging between (MBC = 6.51-45.58 μg/mL) and (MFC = 13.58 μg/mL), respectively, and demonstrated bactericidal and fungicidal behavior. The in-silico ADMET study for ligand and two complexes were determined and showed non-AMES toxicity, non-carcinogenic, and obey the rule of five. A comparative docking study provided more insight into the binding mechanisms and suggested that antimicrobial activity may be due to inhibition of different targets.


Perineurial cell differentiation in benign tumors and tumorlike proliferation of peripheral nerves.
An unusual, benign, spindle cell peripheral nerve sheath tumor (PNST) is reported that on ultrastructural examination was composed only of perineurial cells. The neoplastic cells showed positive immunoreactivity for S-100 protein and negative immunoreactivity for epithelial membrane antigen; this is not the expected immunophenotype of a perineurioma. Continued examination of benign PNSTs using electron microscopy and immunohistochemistry has the potential to reveal additional variations in the cellular composition and immunophenotype of these soft tissue tumors. PNSTs such as the one described will renew the debate about the cytogenesis of the perineurial cell and its role in PNSTs.


The association between TP53 Arg72pro polymorphism and non-melanoma skin cancer risk: a meta-analysis including 7,107 subjects.
The p53 gene is a critical molecular in the protection of cells from DNA damage due to Ultraviolet (UV) exposure, and TP53 mutation is very common in non-melanoma skin cancer. To assess the association between the TP53 Arg72Pro polymorphism and non-melanoma skin cancer (NMSC) risk. We performed this meta-analysis with 13 case-control studies involving 3,520 cases and 3,587 controls. Our meta-analysis showed that TP53 Arg72Pro polymorphism was not associated with non-melanoma skin cancer susceptibility in overall population.(for Arg/Arg vs. Pro/Pro: OR 0.98, 95% CI 0.80-1.19; for Arg/Pro vs. Pro/Pro: OR 0.99, 95% CI 0.84-1.17; for the recessive model Arg/Arg vs. Arg/Pro + Pro/Pro: OR 1.10, 95% CI 0.89-1.35; for the dominant model Arg/Arg + Arg/Pro vs. Pro/Pro: OR 1.00, 95% CI 0.85-1.18). We also detected no effect of this polymorphism on any subtype of non-melanoma skin cancer, such as squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furthermore, no significant association in any subgroup was detected in stratified analyses according to ethnicity. However, in the stratified analysis by sample collection resources, Arg/Arg carriers from tumor tissue subgroup had 3.42 times risk of cancer (95% CI, 1.19 to 9.84) as compared with the variant type Pro/Pro in NMSC. TP53 Arg72Pro polymorphism may have little involvement in the pathogenesis of NMSC, regardless of type, including SCC, and BCC.


Birth Observation Among African American Women Prior to Pregnancy.
A focused ethnography among African American college students who had observed a live birth prior to their own pregnancy was pursued. Women described two reasons to attend births: curiosity about birth, or a desire to support the birth mother. Women attended the births of friends, family members, or saw their mother give birth to a younger sibling. Themes included pain, operative or traumatic birth, and surprise at the length and/or stages of labor. Some language suggested lingering trauma. Future expectations included painful labor, operative birth or damage, or traumatic labor and birth. Other women felt closer to the infant, or felt more prepared for their own births after observing birth. Prior personal experiences at birth should be explored prenatally.


Improved urine screening using a combination of leukocyte esterase and the Lumac system.
Three rapid urine screening tests, leukocyte esterase, nitrite, and the Lumac System for detection of bacterial ATP, were evaluated alone and in combination to determine their utility in screening urine specimens from male patients for bacteruria. The combination of leukocyte esterase and Lumac testing resulted in significant improvement in the sensitivity of urine screening over each test individually and the combination of leukocyte esterase and nitrite. The leukocyte esterase/Lumac combination detected 98% of those specimens with greater than or equal to 10(5) CFU/ml and had a negative predictive value of 99%. The results obtained from this type of testing can be used with confidence to minimize the number of urine specimens cultured and to provide rapid reporting of negative results.


Metal artifact reduction in musculoskeletal magnetic resonance imaging.
Many strategies can be employed to reduce the size and scale of metal susceptibility artifacts in the vicinity of orthopedic hardware; factors include selection of metal hardware material, patient positioning, and MRI sequence adjustments and techniques. The adjustments to sequence parameters include high spatial resolution fast spin echo sequences with minimal interecho spacing and increased receiver bandwidth. Frequency and phase encoding gradients can be orientated so misregistration artifacts arising from the metal are directed away from areas of anticipated clinical diagnostic interest. Complications arising in the vicinity of metallic hardware, including loosening, can be assessed after implication of these metal artifact reduction techniques.


Ethnobotany, phytochemistry and neuropharmacological effects of Petiveria alliacea L. (Phytolaccaceae): A review.
Petiveria alliacea L. commonly grows in the tropical regions of the Americas such as the Amazon forest, Central America, Caribbean islands and Mexico, as well as specific regions of Africa. Popularly known by several different names including 'mucuracaá', 'guiné' and 'pipi', P. alliacea has been used in traditional medicine for the treatment of various central nervous system (CNS) disorders, such as anxiety, pain, memory deficits and seizures, as well as for its anaesthetic and sedative properties. Furthermore, the use of this species for religious ceremonies has been reported since the era of slavery in the Americas. Therefore, the present review aims to provide a critical and comprehensive overview of the ethnobotany, phytochemistry and pharmacological properties of P. alliacea, focusing on CNS pharmacological effects, in order to identify scientific lacunae and to open new perspectives for future research. A literature search was performed on P. alliacea using ethnobotanical textbooks, published articles in peer-reviewed journals, unpublished materials, government survey reports and scientific databases such as PubMed, Scopus, Web of Science, Science Direct and Google Scholar. The Plant List, International Plant Name Index and Kew Botanical Garden Plant name databases were used to validate the scientific names. Crude extracts, fractions and phytochemical constituents isolated from various parts of P. alliacea show a wide spectrum of neuropharmacological activities including anxiolytic, antidepressant, antinociceptive and anti-seizure, and as cognitive enhancers. Phytochemistry studies of P. alliacea indicate that this plant contains a diversity of biologically active compounds, with qualitative and quantitative variations of the major compounds depending on the region of collection and the harvest season, such as essential oil (Petiverina), saponinic glycosides, isoarborinol-triterpene, isoarborinol-acetate, isoarborinol-cinnamate, steroids, alkaloids, flavonoids and tannins. Root chemical analyses have revealed coumarins, benzyl-hydroxy-ethyl-trisulphide, benzaldehyde, benzoic acid, dibenzyl trisulphide, potassium nitrate, b-sitosterol, isoarborinol, isoarborinol-acetate, isoarborinol-cinnamate, polyphenols, trithiolaniacine, glucose and glycine. Many traditional uses of P. alliacea have now been validated by modern pharmacology research. The available data reviewed here support the emergence of P. alliacea as a potential source for the treatment of different CNS disorders including anxiety, depression, pain, epilepsy and memory impairments. However, further studies are certainly required to improve the knowledge about the mechanisms of action, toxicity and efficacy of the plant as well as about its bioactive compounds before it can be approved in terms of its safety for therapeutic applications.


Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating in vitro and in vivo studies.
Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) coatings have been used to improve the degradation resistance and the biocompatibility of Mg materials. This study focuses on the comparison and correlation of the in vitro and in vivo degradation and biocompatibility behaviors of these materials. A CaP coating consisting of dicalcium phosphate dihydrate (DCPD) was deposited on an AZ60 Mg alloy by the chemical conversion method. Then, the in vitro degradation testing including electrochemical and immersion tests, and in vivo implantation of the CaP coated Mg alloy were conducted to compare the degradation behaviors. Next, the in vitro cell behavior and in vivo bone tissue response were also compared on both uncoated and CaP-coated Mg samples. Data showed that the CaP coating provided the Mg alloy with significantly better biodegradation behavior and biocompatibility. The in vitro and in vivo biocompatibility tests exhibited good consistency while not the case for biodegradation. Results showed that the in vitro electrochemical test could be a quick screening tool for the biodegradation rate, while the in vitro immersion degradation rate was often 2-4 folds faster than the in vivo degradation rate.


Trends and current status in childhood mortality. United States, 1900-85.
Mortality statistics for children 1-19 years of age by race, sex, and cause of death are analyzed focusing on differences in external and natural causes. General trends from 1900-68 as well as trends in leading causes of death for 1968-85 are examined. Geographic variation by cause of death and cross-national comparisons are also presented.


A multi-biomarker approach for the early assessment of the toxicity of hospital wastewater using the freshwater organism Daphnia magna.
Hospital wastewater (HWW) contains different hazardous substances resulting from a combination of medical and non-medical activities of hospitals, including pharmaceutical residues. These substances may represent a threat to the aquatic environment if they do not follow specific treatment processes. Therefore, we aimed to investigate the effects of the untreated effluent collected from a general hospital in Mahdia City (Tunisia) on neonatal stages of the freshwater crustacean Daphnia magna. Test organisms were exposed to three proportions (3.12%, 6.25%, and 12.5% v/v) of HWW. After 48 h of exposure, a battery of biomarkers was measured, including the quantification of antioxidant enzymes [catalase (CAT) and total and selenium-dependent glutathione peroxidase (total GPx; Se-GPx)], phase II biotransformation isoenzymes glutathione-S-transferases (GSTs), cyclooxygenases (COX) involved in the regulation of the inflammatory process, and total cholinesterases (ChEs) activities. Lipid peroxidation (LPO) was measured to estimate oxidative damage. The here-obtained results showed significant decreases of CAT and GSTs activities and also on LPO content in daphnids, whereas Se-GPx activity was significantly increased in a dose-dependent manner. Impairment of cholinesterasic and COX activities were also observed, with a significant decrease of ChEs and an increase of COX enzymatic activities. Considering these findings, HWW was capable of inducing an imbalance of the antioxidant defense system, but without resulting in oxidative damage in test organisms, suggesting that peroxidases and alternative detoxifying pathways were able to prevent the oxidant potential of several drugs, which were found in the tested effluents. In general, this study demonstrated the toxicity of hospital effluents, measured in terms of the potential impairment of key pathways, namely neurotransmission, antioxidant defense, and inflammatory homeostasis of crustaceans.


Individual differences in offensive aggression in golden hamsters: a model of reactive and impulsive aggression?
In humans, reactive aggression is associated with impulsivity. The purpose of this study is to relate reactive and impulsive aggression in humans with offensive aggression in animals and identify neurobiological correlates associated with certain forms of the behavior. We predicted that individual differences in offensive aggression are associated with individual differences in impulsivity. Adult male hamsters were repeatedly tested for offensive responses and divided into High-Aggression or Low-Aggression groups. They were then trained and tested under a delay-discounting paradigm to assess impulsivity. High-Aggression animals consistently attacked and bit more frequently and faster, and showed highly repetitive behavior, indicated by repeated attacks per contact bout. In addition, these animals engaged in more fragmented and shorter contact bouts. During impulsivity testing, High-Aggression animals preferred immediate smaller rewards over delayed larger rewards. Furthermore, 5-HT and vasopressin (AVP) innervation was compared between the groups. High-Aggression animals showed decreased 5-HT varicosities in several key brain areas involved in aggressive and/or impulsive behavior and decreased AVP fibers in the anterior hypothalamus. Together, these data show a convergence of behavioral phenotypes through individual differences in offensive aggression and impulsivity. As such, this association provides support for an animal model of reactive and impulsive aggression. Furthermore, this behavioral convergence is supported by a concurrent reduction in 5-HT innervation of brain areas controlling aggression and impulsivity, providing a common neural mechanism for this phenotype.


ITPA (inosine triphosphate pyrophosphatase): from surveillance of nucleotide pools to human disease and pharmacogenetics.
Cellular nucleotide pools are often contaminated by base analog nucleotides which interfere with a plethora of biological reactions, from DNA and RNA synthesis to cellular signaling. An evolutionarily conserved inosine triphosphate pyrophosphatase (ITPA) removes the non-canonical purine (d)NTPs inosine triphosphate and xanthosine triphosphate by hydrolyzing them into their monophosphate form and pyrophosphate. Mutations in the ITPA orthologs in model organisms lead to genetic instability and, in mice, to severe developmental anomalies. In humans there is genetic polymorphism in ITPA. One allele leads to a proline to threonine substitution at amino acid 32 and causes varying degrees of ITPA deficiency in tissues and plays a role in patients' response to drugs. Structural analysis of this mutant protein reveals that the protein is destabilized by the formation of a cavity in its hydrophobic core. The Pro32Thr allele is thought to cause the observed dominant negative effect because the resulting active enzyme monomer targets both homo- and heterodimers to degradation.


Preoperative magnetic resonance imaging predicts clinicopathological parameters and stages of endometrial carcinomas.
We investigated the agreement and accuracy of preoperative magnetic resonance imaging (MRI) with postoperative pathological characteristics and stages of endometrial endometrioid carcinoma (EEC). We recruited 527 women with EEC who underwent staging surgery at a single medical institution. The preoperative MRI, stages, and clinical and pathological parameters, including myometrial invasion (MI), cervical invasion (CI), adnexal metastasis (AM), intra-abdominal metastasis, and pelvic and/or para-aortic nodal metastasis, were recorded and analyzed. The agreement and accuracy between the preoperative MRI findings and these parameters and stages were assessed. The rate of the preoperative MRI-based clinical stage matching the postoperative surgical stage was 85.2% in International Federation of Gynecology and Obstetrics stage IA, 51.9% in stage IB, 35.5% in stage II, 5.3% in stage IIIA, 33.3% in stage IIIB, 28.6% in stage IIIC1, 64.3% in stage IIIC2, and 93.8% in stage IVB. The consistency between radiologists and pathologists was 80.5% for deep MI, 91.5% for cervical invasion, 92.2% for adnexal metastasis, 98.9% for intra-abdominal metastasis, and 87.5% and 92.2% for pelvic and para-aortic nodal metastases, respectively. The negative predictive value of intra-abdominal metastasis was the highest with 99.8%. Preoperative MRI could be an excellent tool for routine preoperative assessment to predict pathological parameters and stages of EEC, especially in excluding intra-abdominal metastatic disease.


Equilibrium binding analysis of neural cell adhesion molecule binding to heparin.
The kinetics of neural cell adhesion molecule (NCAM) binding to heparin were studied in a heparin-Sepharose-based solid-phase binding assay. The observed binding is time dependent and saturable. A binding constant of 5.2 +/- 1.4 X 10(-8) M is observed for binding of newborn rat NCAM to heparin. This is approximately 25 times lower than the binding constant determined for newborn rat NCAM homophilic binding. Both Scatchard and Hill plot analyses suggest the presence of only one binding site. Fab' fragments of antibodies to rat NCAM significantly inhibit binding, a result indicating that a specific site on NCAM is involved in binding to heparin. The binding is inhibited by heparin (IC50, approximately 5 micrograms/ml), whereas chondroitin sulfate is a less potent inhibitor (IC50, approximately 15 micrograms/ml).


Introduction: An update on bone metabolism and osteoporosis.
Osteoporosis continues to be a major public health challenge in both women and men. There are more than 2 million low-impact fractures in the United States every year, 39% of which occur in men. The mortality rate in the first year after hip fracture is estimated at 20% to 25% in women and is even higher in men. The goal of this Views and Reviews is to provide an update regarding bone metabolism and contemporary approaches to prevention and treatment of osteoporosis.


Neuromuscular blocking agents and monitoring in the equine patient.
This article briefly reviews the physiology of the neuromuscular junction and the pharmacologic mechanisms of neuromuscular blocking agents. The clinical use of modern agents is discussed. Monitoring techniques used to assess the level of neuromuscular block and to exclude residual paralysis at the end of an anesthetic procedure are reviewed.


Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.
Macrophages play important roles in the progression of intervertebral disc herniation and radiculopathy. To better understand the roles of macrophages in this process, we developed a new mouse model that mimics human radiculopathy. A preclinical randomized animal study. Three types of surgeries were performed in randomly assigned Balb/c mice. These were spinal nerve exposure, traditional anterior disc puncture, and lateral disc puncture with nerve exposure (n=16/group). For the nerve exposure group, the left L5 spinal nerve was exposed without disc injury. For the traditional anterior puncture, L5/6 disc was punctured by an anterior approach as previously established. For lateral puncture with nerve exposure, the left L5 spinal nerve was exposed by removing the psoas major muscle fibers, and the L5/6 disc was punctured laterally on the left side with a 30G needle, allowing the nucleus to protrude toward the L5 spinal nerve. Mechanical hyperalgesia (pain sensitivity) of hind paws was assessed with electronic von Frey assay on alternative day for up to 2 weeks. MRI, histology, and immunostaining were performed to confirm disc herniation and inflammation. Ipsilateral pain in the lateral puncture with nerve exposure group was significantly greater than the other groups. Pro-inflammatory cytokines IL-1β and IL-6 were markedly elevated at the hernia sites of both puncture groups and the spinal nerve of lateral puncture with never exposure group on postoperative day 7. Heterogeneous populations of macrophages were detected in the infiltration tissue of this mouse model and in tissue from patients undergone discectomy. We have established a new mouse model that mimics human radiculopathy and demonstrated that a mixed phenotype of macrophages contribute to the pathogenesis of acute discogenic radiculopathy. This study provides a clinically relevant in vivo animal model to elucidate complex interactions of disc herniation and radicular pain, which may present opportunities for the development of macrophage-anchored therapeutics to manage radiculopathy.


[Chemical Constituents from Young Fruits of Citrus maxima cv. Shatian].
To investigate the chemical constituents from the young fruits of Citrus maxima cv. Shatian. The chemical constituents were isolated and purified by silica gel column chromatography and recrystallization, and their structures were identified on the basis of physicochemical properties and spectral analysis. Seven compounds were isolated and identified as naringenin (I), marmin (II), naringin (III), β-sitosterol (IV) 5,7-dihydroxylcoumarin (V) 1, 3,5-trihydroxyhenzene (VI) and xanthotoxol (VII). Except compound III, all compounds are isolated from the young fruits of Citrus maxima cv. Shatian for the first time.


Present situation of vector-control management in Bangladesh: a wake up call.
Kala-azar or visceral leishmaniasis is one of the major vector-borne diseases in Bangladesh. The disease is transmitted by sandfly. The incidence of the disease, which has been increasing since the early eighties, must be reduced by taking adequate vector-control measures. The objective of the present study was to identify the favorable factors and the constraints of present vector-control management in Bangladesh. Purposively selected senior entomologist and retired senior entomologist at central level, civil surgeons, entotechnicians, health inspectors and spray men from kala-azar-endemic districts, community leaders, and NGO representatives were key informants of the study. A household survey to learn about knowledge and perceptions of the people about kala-azar vector was carried out, using a structured questionnaire, in 202 randomly selected households. Practically, there was no vector-control activity in the nine most kala-azar-endemic districts of Bangladesh. Inadequate human resources, lack of logistics, and unavailability of funds for vector control were the major constraints. Community perception about kala-azar vector was poor. However, the use of bednets in the community was high. No private organization was involved in kala-azar vector control. Knowledge of the spray men about the insecticide-spraying technique was also unsatisfactory. Kala-azar vector control in Bangladesh needs immediate attention of policy-makers and donors, otherwise, elimination of kala-azar from the country by 2015 may not be achievable.


Does cholesterol preferentially pack in lipid domains with saturated sphingomyelin over phosphatidylcholine? A comprehensive monolayer study combined with grazing incidence X-ray diffraction and Brewster angle microscopy experiments.
In this work, the Langmuir monolayers were used as a model for the analysis of the influence of cholesterol on 1,2-distearoyl-sn-glycero-3-phosphocholine - DSPC and stearoyl sphingomyelin - SSM, as well as their equimolar mixture. The aim of these studies was to compare the affinity of cholesterol to sphingomyelin and phosphatidylcholine and discuss the effectiveness of cholesterol packing with these phospholipids. The experiments involved the registration of the surface pressure-area isotherms combined with the application of Brewster angle microscopy (BAM) images and grazing incidence X-ray diffraction methods. We have performed a thorough analysis of the properties of both one-component DSPC and SSM films as well as their 1:1 mixture. Next, the effect of cholesterol on these systems was verified based on the results for 2:1 SSM/Chol, 2:1 DSPC/Chol, and 1:1:1 DSPC/SSM/Chol mixtures. It was found that both phospholipids form highly condensed monolayers, however, they differ in the orientation of acyl chains, namely the acyl chains are more tilted in DSPC film as compared to SSM monolayer as well as DSPC/SSM mixture. Furthermore, the area contraction provoked by the addition of cholesterol was found to be more pronounced for DSPC monolayer than in DSPC/SSM and SSM films. However, all the collected results allow one to postulate that the ability of cholesterol to form ordered domains with DSPC and SSM is similar and is predominantly driven by hydrophobic forces between molecules. The differences in the area condensation induced by cholesterol on the studied phospholipids films results from differences in molecular organization of pure phospholipids films rather than specific cholesterol-phospholipid interactions.


Trauma in children and adolescents: risk and treatment of psychiatric sequelae.
The recent wave of terrorism affecting the United States and other countries raises concerns about the welfare of children and adolescents. This review is designed to address such concerns by summarizing data from two scientific areas. First, a series of recent studies examine psychiatric outcomes over time in children exposed to various forms of trauma. This review summarizes data on the various psychiatric consequences of childhood exposure to trauma, with specific emphasis on identifying factors that predict psychiatric outcome. Prior studies suggest that level of exposure, evidence of psychopathology before trauma exposure, and disruption in social support networks consistently emerge as strong predictors of psychopathology following exposure to trauma. Hence, clinicians might monitor children exposed to trauma most closely when they present with these risk factors. Second, a series of randomized controlled trials documents the beneficial effects of cognitive behavioral therapy (CBT) in children exposed to sexual abuse. When combined with other data from open studies and controlled trials in nontraumatized children, these studies suggest that CBT represents a logical therapeutic option for children developing anxiety symptoms following the recent wave of terrorism. In terms of psychopharmacological treatments, data from randomized controlled trials in traumatized children have not been generated, but recent studies in other groups of children exhibiting symptoms of anxiety or depression suggest the utility of selective serotonin reuptake inhibitors.


Endocarditis due to Aggregatibacter Segnis: a rare case report.
As a member of the HACEK group, Aggregatibacter segnis (A. segnis) is a fastidious Gram-negative coccobacillus that resides in the human oropharyngeal flora. Infective endocarditis caused by A. segnis is rarely reported. A 31-year-old male was admitted to our hospital for a 3-month history of intermittent high fever, chills, and chest distress. On presentation, he was febrile and tachycardic but otherwise with stable vital signs. Physical examination revealed systolic murmurs in the aortic and mitral valve areas. Pitting edema was evident in the lower extremities. Transthoracic echocardiography demonstrated multiple vegetations in the mitral and aortic valves. Severe regurgitation of the aortic valve and left heart dysfunction were also detected. With the suspicion of infective endocarditis and heart failure, we immediately performed microbiological tests and arranged the cardiac replacement surgery. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and metagenomic next-generation sequencing (mNGS) identified A. segnis from the bloodstream. While the surgical specimen culture was negative, the mNGS was positive for A. segnis. The patient was treated with ceftriaxone for four weeks and discharged. He remained clinically well, with laboratory results restored. This is the first report of A. segnis infective endocarditis that combined MALDI-TOF and metagenomic next-generation sequencing in the diagnosis. The hypothesis-independent molecular techniques can outperform conventional tools to prevent diagnostic delay.


linus: Conveniently explore, share, and present large-scale biological trajectory data in a web browser.
In biology, we are often confronted with information-rich, large-scale trajectory data, but exploring and communicating patterns in such data can be a cumbersome task. Ideally, the data should be wrapped with an interactive visualisation in one concise packet that makes it straightforward to create and test hypotheses collaboratively. To address these challenges, we have developed a tool, linus, which makes the process of exploring and sharing 3D trajectories as easy as browsing a website. We provide a python script that reads trajectory data, enriches them with additional features such as edge bundling or custom axes, and generates an interactive web-based visualisation that can be shared online. linus facilitates the collaborative discovery of patterns in complex trajectory data.


Heterophase junction engineering: Enhanced photo-thermal synergistic catalytic performance of CO2 reduction over 1T/2H-MoS2.
Photocatalytic CO2 reduction technology has been proposed as a promising solution to the greenhouse effect and energy crisis. However, the lower quantum efficiency limits its practical applications. Here, we have significantly improved the photocatalytic CO2 reduction performance of MoS2 by coupling the heterophase junction (1T/2H-MoS2) construction and photo-thermal synergy strategies. At 200 °C and 42 mW·cm-2 of 420 nm LED irradiation, the CO production rate of 1T/2H-MoS2 reached 35.3 μmol·g-1·h-1, which was 3.5 and 2.8 times that of 1T-MoS2 and 2H-MoS2, respectively. In addition, only faint CO was detected under sole photo- or sole thermal catalysis conditions. Mechanism studies showed that COOH* was the key intermediate in the photo-thermal synergistic catalytic CO2 reduction over 1T/2H-MoS2. The heterophase junction engineering significantly facilitated the separation of photogenerated carriers, and the introduction of heat accelerated the charge migration and surface reaction rates. Our work provides innovative insights into the catalyst design and mechanism studies for photo-thermal synergistic catalytic CO2 reduction.


Reliability of Thyroid FNAC as a Single Diagnostic Modality: A Systematic Review.
To determine the reliability of thyroid FNAC as a single diagnostic modality in the case of nodular neoplastic lesions of the thyroid. Multiple databases were searched using the MESH terms thyroid*lesion*nodule*neoplasm*fine needle aspiration*histopathology*correlation. Meta analyses, RCTs, cohort or case control studies and case series were searched. 61 studies were examined to verify the search results after applying the inclusion and exclusion criteria. 422 studies were excluded after the first screening, leaving 61 full text articles. These were further analyzed for outcomes, and ultimately 9 studies were chosen for the final synthesis on the basis of clear recommendations given. FNAC as a single modality for the diagnosis of nodular neoplastic thyroid lesions is highly variable and therefore unreliable. The diagnostic yield may be improved if the Bethesda system of reporting is applied.


["Floaterectomy"--pars-plana-vitrectomy for vitreous opacities].
Patients suffer from vitreous opacities, despite good visual acuity. The lack of objective measurements may make it difficult to justify the indication for vitreous surgery. We analysed retrospectively the outcome of 90 eyes/ 67 patients, age 20 - 86 years (mean 60 +/- 19) after pars plana vitrectomy (ppv) for vitreous opacities. Follow-up was 6 - 40 months (mean 19 +/- 9). Additional pathologies (except cataract) possibly affecting the functional outcome were present in 33 % (uveitis 8 %, premacular membrane 10 %, other 15 %). The technique consisted of a standard 3-port vitrectomy (44 % 25-gauge, 46 % 20-gauge). In 78 % ppv was combined with phacoemulsification + IOL implantation. Mean preoperative visual acuity was 0.6, postoperative 1.0 (+ 2.3 lines, p > 0.0001). One eye lost 2 lines. Peripheral retinal tears occurred in 11 %. Long-term complications (12 - 31 months) consisted of premacular membrane formation (1), luxation of the IOL/capsular bag. Secondary interventions included YAG capsulotomy (4) and glaucoma surgery (1). 94 % of all patients (98 % if additional pathologies were excluded) were satisfied with the outcome. Pars plana vitrectomy for vitreous opacities is safe and effective. Careful patient selection is crucial.


Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis.
Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system. Systematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos. Fluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43-0.87) and sertraline (OR=0.56, 95% CI 0.32-0.99). Fluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.


Design, synthesis and biological evaluation of 4-arylamino-pyrimidine derivatives as focal adhesion kinase inhibitors.
A novel series of 4-arylamino-pyrimidine derivatives were designed and synthesized as focal adhesion kinase (FAK) inhibitors under the strategy of structure-based drug design. Most compounds performed excellent anti-proliferative activity against U87-MG cells. Especially, compounds 8d and 9b revealed the highest activity with IC50 values of 0.975 μM and 1.033 μM, which was much potent than the positive control TAE-226 (IC50 = 2.659 μM). On the other hand, the total 27 compounds exhibited low inhibition against human normal 2BS cells. Moreover, compounds 8d and 9b showed outstanding activity against FAK with IC50 values of 0.2438 nM and 0.2691 nM, which was very close to TAE-226 (IC50 = 0.1390 nM). Further studies proved that compounds 8d and 9b could induce U87-MG cell early apoptosis and arrest the cell at G2/M phase. The action mechanism indicated that they could significantly inhibit U87-MG cell clone formation, cell migration, and FAK phosphorylation. Molecular docking and molecular dynamics simulation investigations suggested that compounds 8d and 9b could firmly occupy the ATP binding site of FAK. These findings supported the further researches of compounds 8d and 9b as FAK inhibitors for antitumor drug discovery.


Perception of traffic risks for older and younger adults.
The study examined differences in the perception of traffic risks for older and younger adults. Thirty-four younger participants (mean age 24.7 years) and 30 older participants (mean age 70 years) estimated the number of younger and older people (out of 100,000 people) that were injured in car and pedestrian crashes in a recent year. Both age groups viewed older adults' risks in pedestrian crashes as higher than those of younger adults, and saw older adults' risks in car crashes as identical to the risks for younger adults. Both age groups assessed the risks for their own group quite accurately, but erred in their assessment of the risk for the other group. Older participants tended to overestimate the risk for younger adults, and younger participants tended to underestimate the risk for older adults. These results point to the need to enhance awareness of the age-related increase in traffic risk, which could potentially promote more considerate driving behavior.


Correlation of the efficiency of fatty acid derivatives in suppressing Plasmodium falciparum growth in culture with their inhibitory effect on acyl-CoA synthetase activity.
The intraerythrocytic malaria parasite depends on the surrounding medium for a supply of phospholipid precursors. Efficient inhibition (IC50 7-90 microM) of Plasmodium falciparum growth in vitro was achieved using modified fatty acids. The fatty acid analogues most effective in suppressing P. falciparum growth in culture were also the most active inhibitors of acyl-CoA synthetase from the monkey parasite P. knowlesi.


Heme as a danger molecule in pathogen recognition.
Appropriate control of redox mechanisms are critical for and effective innate immune response, which employs multiple cell types, receptors and molecules that recognize danger signals when they reach the host. Recognition of pathogen-associated pattern molecules (PAMPs) is a fundamental host survival mechanism for efficient elimination of invading pathogens and resolution of the infection and inflammation. In addition to PAMPs, eukaryotic cells contain a plethora of intracellular molecules that are normally secured within the confines of the plasma membrane, but if liberated and encountered in the extracellular milieu can provoke rapid cell activation. These are known as Alarmins or Danger-Associated Molecular Patterns (DAMPs) and can be released actively by cells or passively as a result of sterile cellular injury after trauma, ischemia, or toxin-induced cell rupture. Both PAMPs and DAMPs are recognized by a series of cognate receptors that increase the generation of free radicals and activate specific signaling pathways that result in regulation of a variety of stress response, redox sensitive genes. Multiple mediators released, as cells die include, but are not limited to ATP, hydrogen peroxide, heme, formyl peptides, DNA or mitochondria provide the second signal to amplify immune responses. In this review, we will focus on how sterile and infective stimuli activate the stress response gene heme oxygenase-1 (Hmox1, HO-1), a master gene critical to an appropriate host response that is now recognized as one with enormous therapeutic potential. HO-1 gene expression is regulated in large part by redox-sensitive proteins including but not limited to nrf2. Both PAMPs and DAMPs increase the activation of nrf2 and HO-1. Heme is a powerful pro-oxidant and as such should be qualified as a DAMP. With its degradation by HO-1a molecule of carbon monoxide (CO) is generated that in turn serves as a bioactive signaling molecule. PAMPs such as bacterial endotoxin activate HO-1, and the CO that is generated diffuses into the extracellular milieu where it interacts with bacteria, altering their behavior to increase production of ATP, which then functions as a second signal danger molecule. This two-hit cycle scenario results in efficient and effective activation of host leukocytes to attack and clear bacteria in part via enhanced reactive oxygen species generation. We discuss this intimate communication that occurs between host and bacteria and how these molecules serve as critical regulators of the acute inflammatory response, the overall redox status of the cell, and survival of the host.


A sensitive electrochemical impedance immunosensor for determination of malachite green and leucomalachite green in the aqueous environment.
Application of malachite green (MG) and leucomalachite green (LMG) in fish farm water causes an environmental problem. This study proposes for the first time a sensitive and convenient electrochemical impedance spectroscopy (EIS) method for determining MG and LMG by a bovine serum albumin-decorated gold nanocluster (BSA-AuNC)/antibody composite film-based immunosensor. In order to improve the analytical performance, the glassy carbon electrode (GCE) was modified with 1, 4-phenylenediamine to form a stable layer, and then, BSA-AuNCs were covalently bound to the GCE. An adequate quantity of the polyclonal antibody of LMG was immobilized onto the surface of the BSA-AuNCs by the chemical reaction of EDC/NHS. The sensors can respond to the specific target based on specific covalent bonding. The experimental parameters, such as the pH, incubating concentration, and time, have been investigated and optimized. The calibration curve for LMG was linear in the range of 0.1~10.0 ng/mL with the limit of detection (LOD) 0.03 ng/mL. Furthermore, the sum of MG and LMG was detected in fish farm water by MG reduction. The recovery was between 89.7 % and 99.2 % in spiked samples. The EC sensor method was also compared with the ELISA method and validated by the LC-MS/MS method, which proves its great promise as a field instrument for the rapid monitoring of MG and LMG pollution. Graphical abstract 1, 4-Phenylenediamine and BSA-AuNC/antibody-decorated glassy carbon electrodes have been used for the impedimetric detection of the sum of malachite green and leucomalachite green via specific immuno-binding.


Alteration of the LIS1 gene in Japanese patients with isolated lissencephaly sequence or Miller-Dieker syndrome.
LIS1 is a genetic entity that is responsible for lissencephaly. Previously we have reported isolated lissencephaly sequence (ILS) in a Japanese patient carrying a balanced chromosomal translocation that disrupted the LIS1 gene. We examined mutations of LIS1 in 12 additional Japanese patients, 8 of them with ILS and 4 with Miller-Dieker syndrome (MDS). Fluorescence in situ hybridization (FISH) analysis disclosed deletions of part of the LIS1 gene or of the chromosomal region surrounding it in three of the ILS cases and in three of the MDS cases. In one of the remaining five ILS cases, SSCP analysis and subsequent sequence analysis identified a 1-bp deletion in exon IV, which can be expected to result in premature termination of the gene product. Our results indicate that in Japan, as elsewhere, abnormality of the LIS1 gene is a common cause of MDS/ILS.


Projections from the anteroventral part of the medial amygdaloid nucleus in the rat.
The medial amygdaloid nucleus (Me) integrates pheromonal and olfactory information with gonadal hormone cues, being implicated in social behaviors. It is divided cytoarchitectonically in an anterodorsal, anteroventral (MeAV), posterodorsal and posteroventral part, whose projections are well characterized, except for those of the tiny MeAV. Here, MeAV efferents were examined in the rat with the anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde Fluoro-Gold (FG) tracers and compared with those of other Me parts. The present PHA-L observations show that the MeAV projects profusely to itself, but its projections to other Me parts are modest. In conjunction with FG experiments, they suggest that the MeAV innervates robustly a restricted set of structures it shares with the anterodorsal and/or posteroventral Me. Its major targets are the core of the ventromedial hypothalamic nucleus (especially the dorsomedial and central parts), reached mainly via the stria terminalis, and the amygdalostriatal transition area. In addition, the MeAV innervates substantially the lateral and posterior basomedial amygdaloid nuclei and the intraamygdaloid bed nucleus of the stria terminalis. In contrast to other Me parts, it provides only modest inputs to the main and accessory olfactory systems, medial bed nucleus of the stria terminalis and reproductive hypothalamic nuclei. This anatomical framework suggests that the MeAV may play a role in orienting responses to chemosensory cues and defensive behaviors elicited by the odor of predators.


Microscope transsphenoidal surgery.
The transsphenoidal approach to the pituitary using the microscope has undergone continuous modification since its introduction by Hardy over 50 years ago. It is one of the most effective and safest of major neurosurgical procedures with excellent outcomes and low complication rates. Although being displaced by the endoscopic approach, it remains the 'gold standard' for a number of pituitary conditions such as Cushing's tumours, and for the majority of the remainder, has yet to be overtaken in outcome results by the endoscopic approach. This description of the endonasal 'septal pushover' technique is from an author with experience in nearly 4,000 cases. The anatomy is described, and the step-by-step approach and tumour removal for micro- and pituitary macroadenomas are given. Complications and their avoidance are overviewed.


Visualizing the Geography of HIV Observational Cohorts With Density-Adjusted Cartograms.
Maps are potent tools for describing the spatial distribution of population and disease characteristics and, thereby, for appropriately targeting public health interventions. People with HIV (PWH) tend to live in densely populated and spatially compact areas that may be difficult to visualize on maps using unadjusted geographic or political borders. To illustrate these challenges, we used geographic data from adult PWH at the Vanderbilt Comprehensive Care Clinic (VCCC) in Nashville, Tennessee, and aggregated data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1998 to 2015. We compared choropleth maps that use differential shading of political/geographic boundaries with density-adjusted cartograms that allow for shading and deformed boundaries according to a variable of interest, such as PWH. Cartograms enlarged high-burden areas and shrank low-burden areas of PWH, improving visual interpretation of where to focus HIV prevention and mitigation efforts, when compared with choropleth maps. Cartograms may also demonstrate cohort representativeness of underlying populations (eg, Tennessee for VCCC or the United States for NA-ACCORD), which can guide efforts to assess external validity and improve generalizability. Choropleth maps and cartograms offer powerful visual evidence of the geographic distribution of HIV disease and cohort representation and should be used to guide targeted public health interventions.


Meteorological drivers of respiratory syncytial virus infections in Singapore.
Meteorological drivers are known to affect transmissibility of respiratory viruses including respiratory syncytial virus (RSV), but there are few studies quantifying the role of these drivers. We used daily RSV hospitalization data to estimate the daily effective reproduction number (Rt), a real-time measure of transmissibility, and examined its relationship with environmental drivers in Singapore from 2005 through 2015. We used multivariable regression models to quantify the proportion of the variance in Rt explained by each meteorological driver. After constructing a basic model for RSV seasonality, we found that by adding meteorological variables into this model we were able to explain a further 15% of the variance in RSV transmissibility. Lower and higher value of mean temperature, diurnal temperature range (DTR), precipitation and relative humidity were associated with increased RSV transmissibility, while higher value of maximum wind speed was correlated with decreased RSV transmissibility. We found that a number of meteorological drivers were associated with RSV transmissibility. While indoor conditions may differ from ambient outdoor conditions, our findings are indicative of a role of ambient temperature, humidity and wind speed in affecting RSV transmission that could be biological or could reflect indirect effects via the consequences on time spent indoors.


Associated factors of distress in patients with advanced cancer: A retrospective study.
The objective of this study was to assess the psychosocial distress and associated factors in advanced cancer patients consulting at the outpatient Palliative Care Unit at the National Cancer Institute in Mexico City. A retrospective study was conducted using electronic records (June 2015 to December 2016). A total of 646 patients with advanced cancer during their first visit to the outpatient palliative care unit at the National Cancer Institute in Mexico were evaluated using the Distress Thermometer (DT) and ECOG performance status scores. Overall, 62% were women, with a median age of 57 years, and married (54.8%). The most frequent diagnosis was gastrointestinal cancer (28.6%), and 38.9% had a functional performance status of ECOG 2. The median DT score was 4.0 (IQR = 2-6), with 56% reporting DT scores ≥4. The three most frequent problems ≥4 were sadness (82.6%), feeling weak (81.2%), worry (79.6%), and <4 were feeling weak (57.7%), fatigue (55.6%), and financial security (52.1%). The variables associated with distress according to the multiple logistic regression analysis were problems with housing (OR = 2.661, 95% CI = 1.538-4.602), sadness (OR = 2.533, 95% CI = 1.615-3.973), transportation (OR = 1.732, 95% CI = 1.157-2.591), eating (OR = 1.626, 95% CI = 1.093-2.417), nervousness (OR = 1.547, 95% CI = 1.014-2.360), and sleep (OR = 1.469, 95% CI = 1.980-2.203). The principal factors were related to distress levels, housing problems, transportation issues, and emotional problems such as sadness, nervousness, lower functionality, and younger age. Therefore, psychosocial support is of considerable relevance in palliative care. These findings will help clinicians understand the distress of patients with advanced cancer in palliative care in Latin American countries.


Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis.
Since the ban on some brominated flame retardants (BFRs), phosphorus flame retardants (PFRs), which were responsible for 20% of the flame retardant (FR) consumption in 2006 in Europe, are often proposed as alternatives for BFRs. PFRs can be divided in three main groups, inorganic, organic and halogen containing PFRs. Most of the PFRs have a mechanism of action in the solid phase of burning materials (char formation), but some may also be active in the gas phase. Some PFRs are reactive FRs, which means they are chemically bound to a polymer, whereas others are additive and mixed into the polymer. The focus of this report is limited to the PFRs mentioned in the literature as potential substitutes for BFRs. The physico-chemical properties, applications and production volumes of PFRs are given. Non-halogenated PFRs are often used as plasticisers as well. Limited information is available on the occurrence of PFRs in the environment. For triphenyl phosphate (TPhP), tricresylphosphate (TCP), tris(2-chloroethyl)phosphate (TCEP), tris(chloropropyl)phosphate (TCPP), tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) a number of studies have been performed on their occurrence in air, water and sediment, but limited data were found on their occurrence in biota. Concentrations found for these PFRs in air were up to 47 μg m(-3), in sediment levels up to 24 mg kg(-1) were found, and in surface water concentrations up to 379 ng L(-1). In all these matrices TCPP was dominant. Concentrations found in dust were up to 67 mg kg(-1), with TDCPP being the dominant PFR. PFR concentrations reported were often higher than polybrominated diphenylether (PBDE) concentrations, and the human exposure due to PFR concentrations in indoor air appears to be higher than exposure due to PBDE concentrations in indoor air. Only the Cl-containing PFRs are carcinogenic. Other negative human health effects were found for Cl-containing PFRs as well as for TCP, which suggest that those PFRs would not be suitable alternatives for BFRs. TPhP, diphenylcresylphosphate (DCP) and TCP would not be suitable alternatives either, because they are considered to be toxic to (aquatic) organisms. Diethylphosphinic acid is, just like TCEP, considered to be very persistent. From an environmental perspective, resorcinol-bis(diphenylphosphate) (RDP), bisphenol-A diphenyl phosphate (BADP) and melamine polyphosphate, may be suitable good substitutes for BFRs. Information on PFR analysis in air, water and sediment is limited to TCEP, TCPP, TPhP, TCP and some other organophosphate esters. For air sampling passive samplers have been used as well as solid phase extraction (SPE) membranes, SPE cartridges, and solid phase micro-extraction (SPME). For extraction of PFRs from water SPE is recommended, because this method gives good recoveries (67-105%) and acceptable relative standard deviations (RSDs) (<20%), and offers the option of on-line coupling with a detection system. For the extraction of PFRs from sediment microwave-assisted extraction (MAE) is recommended. The recoveries (78-105%) and RSDs (3-8%) are good and the method is faster and requires less solvent compared to other methods. For the final instrumental analysis of PFRs, gas chromatography-flame photometric detection (GC-FPD), GC-nitrogen-phosphorus detection (NPD), GC-atomic emission detection (AED), GC-mass spectrometry (MS) as well as liquid chromatography (LC)-MS/MS and GC-Inductively-coupled plasma-MS (ICP-MS) are used. GC-ICP-MS is a promising method, because it provides much less complex chromatograms while offering the same recoveries and limits of detection (LOD) (instrumental LOD is 5-10 ng mL(-1)) compared to GC-NPD and GC-MS, which are frequently used methods for PFR analysis. GC-MS offers a higher selectivity than GC-NPD and the possibility of using isotopically labeled compounds for quantification.


Opposite modulation by tachykinin (NK1) and CGRP receptors of sympathetic control of mouse vas deferens motility.
Electrical field stimulation of isolated mouse vas deferens elicited sympathetic twitch whose amplitude was transiently enhanced by the selective tachykinin NK1 receptor agonist, [Sar9,Met(O2)11]substance P (0.3-30 nM), but not by selective NK2 and NK3 receptor agonists. Potentiation by [Sar9,Met(O2)11]substance P was antagonized by (+/-)-CP 96,345 [(2S,3S)-cis-2-(diphenylmethyl)-N- [(2-methoxyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine] (IC50 = 0.1 microM). On the other hand, electrical field stimulation-induced contractions were inhibited by calcitonin gene-related peptide, CGRP (0.1-30 nM), and this action was reduced by its antagonist, human CGRP-(8-37) (3 microM). [Sar9,Met(O2)11]substance P (3 nM) did not affect either high-K+ or noradrenaline-induced contraction, while CGRP (3 nM) significantly reduced the noradrenaline-induced motor response. Capsaicin (1 microM) inhibited sympathetic twitches, and this effect was partially antagonized by human CGRP-(8-37). In the presence of this antagonist, capsaicin induced a short-living and (+/-)-CP 96,345-sensitive twitch enhancement. These data suggest that the sympathetic control of mouse vas deferens motility can be modulated in an opposite manner by tachykinin NK1 (prejunctionally located) and by CGRP (pre- and/or postjunctionally located) receptors.


Use of low-value pediatric services in the Military Health System.
Low-value care (LVC) is understudied in pediatric populations and in the Military Health System (MHS). This cross-sectional study applies previously developed measures of pediatric LVC diagnostic tests, procedures, and treatments to children receiving care within the direct and purchased care environments of the MHS. We queried the MHS Data Repository (MDR) to identify children (n = 1,111,534) who received one or more of 20 previously described types of LVC in fiscal year 2015. We calculated the proportion of eligible children and all children who received the service at least once during fiscal year 2015. Among children eligible for each measure, we used logistic regressions to calculate the adjusted odds ratios (AOR) for receiving LVC at least once during fiscal year 2015 in direct versus purchased care. All 20 measures of pediatric LVC were found in the MDR. Of the 1,111,534 eligible children identified, 15.41% received at least one LVC service, and the two most common procedures were cough and cold medications in children under 6 years and acid blockers for infants with uncomplicated gastroesophageal reflux. Eighteen of the 20 measures of pediatric LVC were eligible for comparison across care environments: 6 were significantly more likely to be delivered in direct care and 10 were significantly more likely to be delivered in purchased care. The greatest differences between direct and purchased care were seen in respiratory syncytial virus testing in children with bronchiolitis (AOR = 21.01, 95% CI = 12.23-36.10) and blood tests in children with simple febrile seizure (AOR = 24.44, 95% CI = 5.49-108.82). A notably greater difference of inappropriate antibiotic prescribing was seen in purchased versus direct care. Significant differences existed between provision of LVC services in direct and purchased care, unlike previous studies showing little difference between publicly and privately insured children. In fiscal year 2015, 1 in 7 children received one of 20 types of LVC. These proportions are higher than prior estimates from privately and publicly insured children, suggesting the particular need to focus on decreasing wasteful care in the MHS. Collectively, these studies demonstrate the high prevalence of LVC in children and the necessity of reducing potentially harmful care in this vulnerable population.


Whole-object fluorescence lifetime setup for efficient non-imaging quantitative intracellular fluorophore measurements.
In the present study we introduce a Whole-Object Fluorescence Life Time (wo-FLT) measurement approach for ease and a relatively inexpensive method of tracing alterations in intracellular fluorophore distribution and in the physical-chemical features of the microenvironments hosting the fluorophore. Two common fluorophores, Rhodamine 123 and Acridine Orange, were used to stain U937 cells which were incubated, with and without either Carbonyl cyanide 3-chlorphenylhydrazon or the apoptosis inducer H(2)O(2). The wo-FLT, which is a non-imaging quantitative measurement, was able to detect several fluorescence decay components and corresponding weights in a single cell resolution. Following cell treatment, both decay time and weight were altered. Results suggest that the prominent factor responsible for these alterations and in some cases to a shift in emission spectrum as well, is the intracellular fluorophore local concentration. In this study it was demonstrated that the proposed wo-FLT method is superior to color fluorescence based imaging in cases where the emission spectrum of a fluorophore remains unchanged during the investigated process. The proposed wo-FLT approach may be of particular importance when direct imaging is impossible.


Molecular regulation of ZmMs7 required for maize male fertility and development of a dominant male-sterility system in multiple species.
Understanding the molecular basis of male sterility and developing practical male-sterility systems are essential for heterosis utilization and commercial hybrid seed production in crops. Here, we report molecular regulation by genic male-sterility gene maize male sterility 7 (ZmMs7) and its application for developing a dominant male-sterility system in multiple species. ZmMs7 is specifically expressed in maize anthers, encodes a plant homeodomain (PHD) finger protein that functions as a transcriptional activator, and plays a key role in tapetal development and pollen exine formation. ZmMs7 can interact with maize nuclear factor Y (NF-Y) subunits to form ZmMs7-NF-YA6-YB2-YC9/12/15 protein complexes that activate target genes by directly binding to CCAAT box in their promoter regions. Premature expression of ZmMs7 in maize by an anther-specific promoter p5126 results in dominant and complete male sterility but normal vegetative growth and female fertility. Early expression of ZmMs7 downstream genes induced by prematurely expressed ZmMs7 leads to abnormal tapetal development and pollen exine formation in p5126-ZmMs7 maize lines. The p5126-ZmMs7 transgenic rice and Arabidopsis plants display similar dominant male sterility. Meanwhile, the mCherry gene coupled with p5126-ZmMs7 facilitates the sorting of dominant sterility seeds based on fluorescent selection. In addition, both the ms7-6007 recessive male-sterility line and p5126-ZmMs7M dominant male-sterility line are highly stable under different genetic germplasms and thus applicable for hybrid maize breeding. Together, our work provides insight into the mechanisms of anther and pollen development and a promising technology for hybrid seed production in crops.


CALIBRATION AND USE OF A PENCIL-TYPE CT CHAMBER: EFFECT OF THE PMMA BODY PHANTOM.
A pencil-type ionization chamber commonly used in computed tomography (CT) dosimetry is usually calibrated free in air, but used inside a PMMA CT phantom. Measurements and Monte Carlo simulations are used to investigate the validity of chamber calibration in this situation where the body phantom modifies the x-ray spectrum impinging on the chamber. The results for the PTW 30009 chamber indicate that the additional uncertainty in CT dose index (CTDIw) measurement introduced by the phantom is ~1% or less. The pencil chamber used in CTDIw measurements should have a flat energy response down to at least 30 keV photon energy to avoid excessive increase in measurement uncertainty.


The vestibulo-ocular reflex and its possible roles in space motion sickness.
Prolonged exposure to an inappropriate vestibulo-ocular reflex (VOR) will usually lead to motion sickness, and it has been predicted on theoretical grounds that VOR gain may be decreased in weightlessness. While experiments during parabolic flight in aircraft tend to confirm this prediction, experiments during orbital spaceflight have led to apparently contradictory results. It is suggested that VOR gain is reduced initially, but that rapid compensatory mechanisms restore it to normal within minutes of reaching weightlessness. However, even though this process may lead to the rapid return of functionally normal gaze stability, it may not protect against the development of motion sickness.


An ophthalmologist's guide to understanding antibiotic susceptibility and minimum inhibitory concentration data.
To address the need to establish appropriate evaluation criteria for analyzing in vitro antibiotic susceptibility based on original data. In vitro laboratory investigation. Bacterial isolates from patients with conjunctivitis. Minimum inhibitory concentrations (MICs), descriptive statistics, antibiotic susceptibility, potency, and statistical analysis. Minimum inhibitory concentrations were determined for 80 bacterial conjunctivitis isolates to moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin. Using the MIC values, descriptive statistics (median, MIC50, MIC90, mode, range), antibiotic susceptibility, and potency of each antibiotic were calculated for each bacterial group. The data were analyzed statistically using appropriate randomization and nonparametric tests. The descriptive statistics of gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) followed a consistent trend where the median, MIC50, MIC90, and mode demonstrated the lowest values, in all instances, for moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin. The descriptive statistics for Haemophilus species (the predominant gram-negative bacteria implicated in conjunctivitis) did not describe any consistent trend. In contrast, antibiotic susceptibility testing did not demonstrate any advantage among the 5 fluorquinolones tested, except for moxifloxacin in the S. aureus fluoroquinolone-resistant group. Potency studies indicated that moxifloxacin and gatifloxacin were the most potent for gram-positive bacteria, whereas gatifloxacin and ciprofloxacin were the most potent for Haemophilus species. In the absence of human clinical trial data to guide care, in vitro susceptibility data should be analyzed with a set of descriptive statistics along with a nonparametric statistical analysis. No single parameter or test should be relied upon in all instances to demonstrate the in vitro superiority of one antibiotic over another. In this study, fourth-generation fluoroquinolones did have some potency advantages over second-generation fluoroquinolones against gram-positive conjunctival bacterial isolates, but not for Haemophilus isolates.


Selenium modulates inorganic mercury induced cytotoxicity and intrinsic apoptosis in PC12 cells.
Mercury (Hg) in its all forms, including inorganic Hg (iHg) is an environmental contaminant due to toxicity and diseases in human. However, a little is known about the underlying mechanisms responsible for iHg toxicity. Selenium (Se) is an essential trace element, recognized as an antioxidant and protective agent against metal toxicities. The purpose of this research was to investigate ameliorations of Se counter to iHg-mediated toxicity in PC12 cells. Cytotoxic assays have been shown that iHg (5 μM) caused oxidative stress and intrinsic apoptosis via ROS generation, oxidizing glutathione, damaging DNA, degrading cell membrane integrity, down-regulating mTOR, p-mTOR, akt and ERK1, and up-regulating cleaved caspase 3 and cytochrome c release in PC12 cells 48 h after incubation. Co-treatment of Se (5 μM) inhibited intrinsic apoptosis and oxidative stress induced by iHg (5 μM) via inhibiting ROS formation, boosting GPx contents, increasing reduced glutathione, limiting DNA degradation, improving cell membrane integrity, up-regulating mTOR, p-mTOR, akt, ERK1 and caspase 3, and down-regulating cleaved caspase 3 and cytochrome c leakage in PC12 cells. In conclusion, these results recommended that excessive ROS generation acts a critical role in iHg-influenced oxidative stress and co-treatment of Se attenuates iHg-cytotoxicity through its antioxidant properties.


RNA-Seq analysis of immune-relevant genes in Lateolabrax japonicus during Vibrio anguillarum infection.
Lateolabrax japonicus is one of the main marine aquatic fish species, and is popularly cultured in East Asia due to its highly commercial value. In recent years, because of large-scale and intensive farming and seawater pollution, fish diseases keep breaking out. However, systematic study on L. japonicus immunogenetics is limited due to the deficiency of deep sequencing technologies and genome backgrounds. In this study, the widely analysis at the transcriptome level for L. japonicus that infected with Vibrio anguillarum was performed. In total, 334,388,688 high quality reads were obtained in six libraries (HK-VA, HK-PBS, LI-VA, LI-PBS, SP-VA and SP-PBS) and de novo assembled into 101,860 Unigenes with an average unigene length of 879 bp. Based on sequence similarity 30,142 unigenes (29.59%) were annotated in the public databases. Comparative analysis revealed, 1,202, 3034 and 3519 differentially expressed genes (DEGs) were identified in three comparisons (HK-PBS VS HK-VA, LI-PBS VS LI-VA and SP-PBS VS SP-VA). Enrichment and pathway analysis of the DEGs was also carried out to excavate the candidate genes related to immunity. In conclusion, this study identifies and evaluates dozen of potential immune related pathways and candidate genes, which are indispensable for padding genomic resources of L. japonicus, and would lay the foundation for further studying and illuminating the mechanism of host-pathogen interactions.


Dynamics of muscle growth and regeneration: Lessons from the teleost.
The processes of myogenesis during both development and regeneration share a number of similarities across both amniotes and teleosts. In amniotes, the process of muscle formation is considered largely biphasic, with developmental myogenesis occurring through hyperplastic fibre deposition and postnatal muscle growth driven through hypertrophy of existing fibres. In contrast, teleosts continue generating new muscle fibres during adult myogenesis through a process of eternal hyperplasia using a dedicated stem cell system termed the external cell layer. During developmental and regenerative myogenesis alike, muscle progenitors interact with their niche to receive cues guiding their transition into myoblasts and ultimately mature myofibres. During development, muscle precursors receive input from neighbouring embryological tissues; however, during repair, this role is fulfilled by other injury resident cell types, such as those of the innate immune response. Recent work has focused on the role of macrophages as a pro-regenerative cell type which provides input to muscle satellite cells during regenerative myogenesis. As zebrafish harbour a satellite cell system analogous to that of mammals, the processes of regeneration can be interrogated in vivo with the imaging intensive approaches afforded in the zebrafish system. This review discusses the strengths of zebrafish with a focus on both the similarities and differences to amniote myogenesis during both development and repair.


Nanostructured liquid crystalline formulation as a remarkable new drug delivery system of anti-epileptic drugs for treating children patients.
Development of a new dosage-form of antiepileptic-drugs appropriated for children. Clonazepam (Cl) was formulated as cubosomal-gel (cub-gel) to be used as a patch reservoir through transdermal-route. Cubosomes prepared using glycerol-mono-oleate(GMO)/Pluronic-F127(PF127) mixture. An actual-statistical design was used to investigate the effect of different stabilizing agents (Ethanol and PVA) and surfactant concentration on cubosomes' particle size and entrapping-efficiency. The selected formulae were evaluated by testing particle-morphology, in vitro drug release and stability. Cub-gel was prepared using selected cubosome formulae. The optimal cub-gel subjected to in vitro dissolution, ex-vivo permeation and skin deposition studies followed by studying its pharmacological effect. Using PVA or Et as stabilizers with PF127 significantly decreases the average cubosomes'PS (352 ± 2.8 and 264 ± 2.16 nm) and increases EE (58.97 ± 4.57% and 54.21 ± 3.89%). Cubosomes increase the initial release rate of Cl to ensure rapid therapeutic effect (37.39% and 46.04% in the first hour) followed by a prolonged release till 4 h. Cub-gel containing PVA showed significantly higher Cl-transdermal permeation when compared to Cl-suspension. Moreover, increases the retention-time (89.57% at 48 h) and skin-deposition up to 6-times. It also reduces the epileptic seizures and alters the behavioral parameters induced by pilocarpine. Cubosomal-gel could be considered an innovative dosage-form for Cl through the transdermal route.


Chronic plantar fasciitis: plantar fasciotomy versus gastrocnemius recession.
The purpose of this study was to compare results of partial proximal fasciotomy (PPF) with proximal medial gastrocnemius release (PMGR) in the treatment of chronic plantar fasciitis (CPF). This retrospective study compares 30 patients with CPF that underwent PPF with 30 that underwent isolated PMGR. Both groups were matched in terms of previous treatments and time from onset of symptoms to surgery. Different standardised evaluation scales (VAS, Likert, AOFASh) were used to evaluate results. Plantar fasciotomy had satisfactory results in just 60 % of patients, with an average ten weeks needed to resume work and sports. Patient satisfaction in the PMGR group reached 95 %, being back to work and sports at three weeks on average. Functional and pain scores were considerably better for PMGR and fewer complications registered. In our series, isolated PMGR is a simple and reliable procedure to treat patients with CPF. It provides far better results than conventional fasciotomy with less morbidity and better patient satisfaction, and thus has become our surgical procedure of choice in recalcitrant CPF.


The impact of changing the diagnostic algorithm for TB in Manicaland, Zimbabwe.
Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe. To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time. This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018. The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9-8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to "no results", errors and invalid results was 6.3%, and highly variable across sites. Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time.


Thiol-ene microfluidic chip for fast on-chip sample clean-up, separation and ESI mass spectrometry of peptides and proteins.
Mass spectrometry (MS) is a key technology for sensitive and high-resolution mass analysis of peptides and proteins. Sample clean-up and chromatographic separation is typically performed prior to MS analysis to limit adduct formation and ionization suppression. Usually, this requires a high-pressure LC pump system equipped with expensive metal chromatographic columns placed in-line of an electrospray ionization (ESI) source. Microfluidic devices coupled to MS have gained considerable attention, due to the promise of low manufacturing costs, low sample consumption and channels with a high surface area to volume ratio and tailorable functional groups. Here, we describe a thiol-ene microfluidic chip capable of fast chromatographic sample clean-up, concentration, and separation of complex protein and peptide mixtures with direct on-chip ESI. On-chip reversed-phase chromatography (RPC) was performed through an in-situ polymerized monolith frit for retaining inexpensive commercially available reversed-phase (RP) spherical particles, while on-chip ESI is achieved through an emitter monolithically implemented by precision micro milling. The on-chip integration of both RPC and ESI emitter allowed for a minimization of dead-volumes and enables very fast sample clean-up, efficient ionization, and mass analysis of peptides and proteins from complex matrices.


Comparison of percutaneous gallbladder aspiration with percutaneous cholecystostomy in acute cholecystostomy patients. Can gall bladder aspiration alone be sufficient?
The aim of this study is to compare the efficacy and complication rates of percutaneous gallbladder aspiration (PA) and percutaneous cholecystostomy (PC) in the management of AC and present the experiences of a single third-line center. The results of 159 patients with AC who admitted to our hospital between 2015 and 2020, that underwent PA and PC procedures, because they did not respond to conservative treatment and LC could not be performed, were retrospectively analyzed. Clinical and laboratory data before and 3 days after PC and PA procedure, technical success, complications, response to treatment, duration of hospital stay, and reverse transcriptase-polymerase chain reaction (RT-PCR) test results were recorded. Out of 159 patients, 22 (8 men 14 women) underwent PA procedure and 137 (57 men 80 women) underwent PC. No significant difference was detected between the PA and PC groups in terms of clinical recovery (P: 0.532) and duration of hospital stay (P: 0.138) in 72 h. The technical success of both procedures was 100%. While 20 out of 22 patients with PA were having a noticable recovery, only one was treated with twice PA procedures and a complete recovery was observed (4.5%). Complication rates were low in both groups and were statistically insignificant (P: 1.00). In this pandemic period, PA and PC procedures are effective, reliable, and successful treatment method that can be applied at the bedside for critical patients with AC who are not compatible with surgery, which are safe for health workers and low-risk minimal invasive procedures for patients. In uncomplicated AC patients, PA should be performed, and if there is no response to treatment, PC should be reserved as a salvage procedure. The PC procedure should be performed in patients with AC who have developed complications and are not suitable for surgery.


The role of cholecystectomy in reducing recurrent gallstone pancreatitis.
Endoscopic sphincterotomy (ES) or cholecystectomy can prevent recurrent acute pancreatitis (RAP) in patients with gallstone-related pancreatitis. However, it is unknown whether cholecystectomy after ES offers additional benefit in preventing RAP in these patients. This is a retrospective study to assess whether cholecystectomy can decrease the incidence of RAP in patients with gallstone-related pancreatitis. Records from 139 patients with gallstone-related pancreatitis were analyzed. Of these, 58 patients had gallbladder stones with concomitant common bile duct (CBD) stones and 81 patients had gallbladder stones without CBD stones. Of the 58 patients who had both gallbladder and CBD stones, 37 (63.8 %) did not undergo cholecystectomy after ES (group 1) and 21 patients (36.2 %) did undergo cholecystectomy after ES (group 2). Of the 81 patients who had gallbladder stones but who did not have CBD stones, 54 (66.7 %) did not undergo cholecystectomy (group 3) and 27 (33.3 %) did undergo cholecystectomy (group 4). At the time of analysis, three patients (8.1 %) in group 1 and three patients (14.3 %) in group 2 developed RAP. There was no significant difference in the estimated probability of occurrence of RAP over time between group 1 and group 2 ( P = 0.41). However, there was a significantly higher probability of patients developing RAP over time in group 3 compared with group 4 (6/54 vs. 0/27 respectively, P = 0.04). In patients with gallbladder stones without CBD stones, cholecystectomy can decrease the incidence of RAP. In patients with both gallbladder and CBD stones, however, the risk of RAP was not further reduced by cholecystectomy after ES and complete removal of CBD stones.


CycleGAN for virtual stain transfer: Is seeing really believing?
Digital Pathology is an area prone to high variation due to multiple factors which can strongly affect diagnostic quality and visual appearance of the Whole-Slide-Images (WSIs). The state-of-the art methods to deal with such variation tend to address this through style-transfer inspired approaches. Usually, these solutions directly apply successful approaches from the literature, potentially with some task-related modifications. The majority of the obtained results are visually convincing, however, this paper shows that this is not a guarantee that such images can be directly used for either medical diagnosis or reducing domain shift.This article shows that slight modification in a stain transfer architecture, such as a choice of normalisation layer, while resulting in a variety of visually appealing results, surprisingly greatly effects the ability of a stain transfer model to reduce domain shift. By extensive qualitative and quantitative evaluations, we confirm that translations resulting from different stain transfer architectures are distinct from each other and from the real samples. Therefore conclusions made by visual inspection or pretrained model evaluation might be misleading.


[Physical exercise in old age].
For the prevention of diseases and especially functional deficits in old age, physical activity is a simple, practicable and successful method. With increasing age and frailty or in rehabilitation training, these activities have to be more and more individualized and medically supervised. The paper defines from today's viewpoint suitable activities and the amount of training necessary. Finally, the need for research about physical training in geriatric medicine is pointed out.


Age at menarche and its influencing factors in North Korean female refugees.
Age at menarche is known to be regulated by genetic and environmental factors. To date, no menarcheal data are available on North Korean women. In this cross-sectional survey, we investigated age at menarche and its possible influencing factors in North Korean refugees. Four hundred and eleven North Korean refugees were surveyed at a North Korean female refugee camp using a structured questionnaire within 3 months of immigration. Menarcheal age was requested and the data obtained were analysed with respect to age at interview, region of residence in North Korea, education, food preference and sleep duration. Mean age at menarche was 16.0+/-2.1 years (mean+/-SD). Univariate analysis demonstrated a significant difference in the menarcheal age among the different food preference groups (P=0.0236). Sleep duration was found to be significantly and negatively correlated with age at menarche (R=-0.23, P<0.0001). However, generalized linear model (GLM) analysis revealed that region of residence at menarche (P=0.0209) and sleep duration (P=0.0007) were significant determinants. Food preference played a role as an effect modifier in the relationship between the region of residence at menarche and age at menarche. Age at menarche seemed to be delayed in North Korean refugees. GLM analysis showed that sleep duration and region of residence at menarche were significant influencing factors of age at menarche in this study population.


Mitral and aortic valve prosthetic endocarditis after percutaneous closure of mitral paravalvular leak.
A 67-year-old man presented to our hospital with massive mitral and aortic valve prosthetic endocarditis 2 months after transcatheter percutaneous closure of a mitral paravalvular leak with an Amplatzer duct occluder device (AGA Medical Corp, Plymouth MN). He underwent successful reoperation for valve prosthesis replacement and reconstruction of the anterior fibrous trigone. Although transcatheter treatment of periprosthetic valve defects has been shown to be feasible, follow-up data are still limited. This procedure should be reserved only for patients who are not eligible for open surgical procedures and those with small periprosthetic defects.


Characterization and replication mode determination of the minimal replicon of Tetragenococcus halophila ATCC33315 plasmid pUCL287.
pUCL287 is a cryptic plasmid of Tetragenococcus halophila (formerly Pediococcus halophilus) ATCC33315 of relatively small size (8.7 kb). Its minimal replicon was located on a 1235 bp MamI-EcoRI fragment. This minimal replicon contains a non-translated region, followed by a gene encoding a putative 311 amino acid protein. Deletion experiments showed that the non-translated region corresponds to the replication origin. Determination of the replication mode was carried out in Enterococcus faecalis JH2-2 harboring pUCL287 minimal replicon. The replicating intermediates detected revealed that pUCL287 minimal replicon follows a bidirectional theta replicating mode.


Changes induced by surgical and clinical factors in the pharmacology of intraperitoneal mitomycin C in 145 patients with peritoneal carcinomatosis.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated. The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined. The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma. Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.


Neurobehavioral management of traumatic brain injury in the critical care setting.
Traumatic brain injury (TBI) results in approximately 230,000 hospitalizations annually in the United States. Advances in the acute management of TBI have improved survival after TBI. Many TBI survivors develop neurobehavioral disturbances in the acute post-injury period. Neurobehavioral sequelae present clinical management challenges for critical care professionals. This article defines and describes TBI and reviews its common neuroanatomic and neurobehavioral consequences. These disturbances are organized under the framework of posttraumatic encephalopathy, and the characteristic forms and stages of recovery of this condition are discussed. Recommendations regarding evaluation and management of posttraumatic neurobehavioral problems in the critical care setting are offered.


Accuracy of refractive outcomes using standard or total keratometry for intraocular lens power formulas in conventional cataract surgery.
To evaluate if total keratometry (TK) is better than standard keratometry (K) for predicting an accurate intraocular lens (IOL) refractive outcome in virgin eyes using four IOL power calculation formulas. 447 eyes that underwent monofocal intraocular lens implantation were enrolled in this study. IOLMaster 700 (Carl Zeiss Meditech, Jena, Germany) was used for optical biometry. Prediction error (PE), mean absolute prediction error (MAE), median absolute prediction error (MedAE), proportions of eyes within ± 0.25 diopters (D), ± 0.50 D, ± 0.75 D, ± 1.00 D, ± 2.00 D prediction error, and formula performance index (FPI) were calculated for each K- and TK-based formula. Overall, the accuracy of each TK and K formula was comparable. The MAEs and MedAEs showed no difference between most of the K-based and the TK-based formula; only the MAE of TK was significantly higher than that of K using the Haigis. The percent of eyes within ± 0.25 D PE for TK was not significantly different from that for K. The analysis of PE across various optical dimensions revealed that TK had no effect on the refractive results in eyes with different preoperative axial length, anterior chamber depth, keratometry, and lens thickness. The K-based Barrett Universal II formula performed excellently, showed the leading FPI score, and had the best refractive prediction outcomes among the four formulas. TK and K can be used for IOL power calculation in monofocal IOL implantation cataract surgery in virgin eyes, as both are comparable. In all investigated formulas, the predictive accuracy of TK-based formulas is not superior to that of standard K-based formulas.


Programmed cell death protein receptor and ligands in haematological malignancies - Current status.
The checkpoint inhibitors have been continuously present in haematology for 20 years. From the first description, several of them were enrolled to the list of the oncological drugs. The research on nivolumab, avelumab, durvolumab is still in progress. In the treatment of some diseases, for instance, Hodgkin lymphoma, the programmed death cell pathway has already an important role. During the last years, the guidelines were enriched by using these drugs, both in solid and haematological malignancies. In this review, we present a history of discovery, research and clinical use of this new class of drugs potentially providing a significant change in curability rates of some haematological malignancies.


A mitochondria-targeted derivative of ascorbate: MitoC.
Mitochondrial oxidative damage contributes to a wide range of pathologies. One therapeutic strategy to treat these disorders is targeting antioxidants to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation. To date only hydrophobic antioxidants have been targeted to mitochondria; however, extending this approach to hydrophilic antioxidants offers new therapeutic and research opportunities. Here we report the development and characterization of MitoC, a mitochondria-targeted version of the hydrophilic antioxidant ascorbate. We show that MitoC can be taken up by mitochondria, despite the polarity and acidity of ascorbate, by using a sufficiently hydrophobic link to the TPP moiety. MitoC reacts with a range of reactive species, and within mitochondria is rapidly recycled back to the active ascorbate moiety by the glutathione and thioredoxin systems. Because of this accumulation and recycling MitoC is an effective antioxidant against mitochondrial lipid peroxidation and also decreases aconitase inactivation by superoxide. These findings show that the incorporation of TPP function can be used to target polar and acidic compounds to mitochondria, opening up the delivery of a wide range of bioactive compounds. Furthermore, MitoC has therapeutic potential as a new mitochondria-targeted antioxidant, and is a useful tool to explore the role(s) of ascorbate within mitochondria.


Severely malnourished children with a low weight-for-height have a higher mortality than those with a low mid-upper-arm-circumference: III. Effect of case-load on malnutrition related mortality- policy implications.
Severe acute malnutrition (SAM) is diagnosed when the weight-for-height Z-score (WHZ) is <-3Z of the WHO2006 standards, or a mid-upper-arm circumference (MUAC) of < 115 mm or there is nutritional oedema. Although there has been a move to eliminate WHZ as a diagnostic criterion we have shown that children with a low WHZ have at least as high a mortality risk as those with a low MUAC. Here we take the estimated case fatality rates and published case-loads to estimate the proportion of total SAM related deaths occurring in children that would be excluded from treatment with a MUAC-only policy. The effect of varying case-load and mortality rates on the proportion of all deaths that would occur in admitted children was examined. We used the same calculations to estimate the proportion of all SAM-related deaths that would be excluded with a MUAC-only policy in 48 countries with very different relative case loads for SAM by only MUAC, only WHZ and children with both deficits. The case fatality rates (CFR) are taken from simulations, empirical data and the literature. The relative number of cases of SAM by MUAC alone, WHZ alone and those with both criteria have a dominant effect on the proportion of all SAM-related deaths that would occur in children excluded from treatment by a MUAC-only program. Many countries, particularly in the Sahel, West Africa and South East Asia would fail to identify the majority of SAM-related deaths if a MUAC only program were to be implemented. Globally, the estimated minimum number of deaths that would occur among children excluded from treatment in our analyses is 300,000 annually. The number, proportion or attributable fraction of children excluded from treatment with any change of current policy are the correct indicators to guide policy change. CRFs alone should not be used to guide policy in choosing whether or not to drop WHZ as a diagnostic for SAM. All the criteria for diagnosis of malnutrition need to be retained. It is critical that methods are found to identify those children with a low WHZ, but not a low MUAC, in the community so that they will not remain undetected.


Xylocopa bees in tropical coastal sand dunes: use of resources and their floral syndromes.
Large bees such as species from Xylocopa Latreille are usually associated with pollination in tropical sand dune areas, which frequently present shrubby herbaceous vegetation adapted to conditions of high salinity, high solar radiation and strong winds. We report on the diversity of Xylocopa and the plants they visited to collect nectar and pollen, focusing on the floral syndromes they present in these plants and on the breadth of the trophic niche in a tropical sand dune fragment over the year. The field work was carried out monthly in Baixio (Bahia, Brazil; Northern Coast Environmental Protection Area) from April 2008 to March 2009, over two consecutive days, from 06:30 AM to 05:00 PM. The medium-large body sized Xylocopa (Neoxylocopa) cearensis Ducke and Xylocopa (Schonnherria) subcyanea Pérez were noticeable for their frequency, constancy on the flowers and sharing of plant species. Xylocopa spp. visited plants with flowers of different shapes, colors, inflorescence arrangement and syndromes. However, their resource collections were mainly concentrated on Cuphea brachiata, Waltheria cinerascens, Croton sellowii and Chamaecrista ramosa, which may be considered key species for Xylocopa spp. maintenance in coastal sand dune and restinga environments in Northeast Brazil.


Nitric oxide reduces aluminum toxicity by preventing oxidative stress in the roots of Cassia tora L.
Nitric oxide (NO) as a key signaling molecule has been involved in mediation of various biotic and abiotic stress-induced physiological responses in plants. In the present study, we investigated the effect of NO on Cassia tora L. plants exposed to aluminum (Al). Plants pre-treated for 12 h with 0.4 mM sodium nitroprusside (SNP), an NO donor, and subsequently exposed to 10 microM Al treatment for 24 h exhibited significantly greater root elongation as compared with the plants without SNP treatment. The NO-promoted root elongation was correlated with a decrease in Al accumulation in root apexes. Furthermore, oxidative stress associated with Al treatment increased lipid peroxidation and reactive oxygen species, and the activation of lipoxygenase and antioxidant enzymes was reduced by NO. Such effects were confirmed by the histochemical staining for the detection of peroxidation of lipids and loss of membrane integrity in roots. The ameliorating effect of NO was specific, because the NO scavenger cPTIO [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide] completely reversed the effect of NO on root growth in the presence of Al. These results indicate that NO plays an important role in protecting the plant against Al-induced oxidative stress.


Respiratory effects of intrathecal capsaicin in arthritic and non-arthritic rats.
The study determined the effects of intrathecal injection of 50 micrograms of capsaicin on respiration in rats with adjuvant arthritis as well as in control animals. Whole body plethysmographic measurements of steady-state frequency, tidal volume, and minute volume of respiration were made 3 hours and for up to 11 days after intrathecal injection. Capsaicin increased minute volume within 3 hours of its intrathecal injection in control animals. Intrathecal capsaicin also reduced the respiratory response to adjuvant arthritis in the experimental animals; the latter effect was apparent 11 days after injection. This biphasic pattern of capsaicin effects is consistent with a possible role of substance P in the chronic pain which is presumably associated with adjuvant arthritis in the rat.