A fluorescent probe to simultaneously detect both O-GlcNAcase and phosphatase.
O-GlcNAc modification of proteins often has crosstalk with protein phosphorylation. These posttranslational modifications are highly dynamic events that modulate a wide range of cellular processes. Owing to the physiological and pathological significance of protein O-GlcNAcylation and phosphorylation, we designed the fluorescent probe, βGlcNAc-CM-Rhod-P, to differentially detect activities of O-GlcNAcase (OGA) and phosphatase, enzymes that are responsible for these modifications. βGlcNAc-CM-Rhod-P was comprised of a βGlcNAc-conjugated coumarin (βGlcNAc-CM) acting as an OGA substrate, a phosphorylated rhodol (Rhod-P) as a phosphatase substrate and a piperazine bridge. Because the emission wavelength maxima of CM and Rhod liberated from the probe are greatly different (100 nm), spectral interference is avoided. The results of this study revealed that treatment of βGlcNAc-CM-Rhod-P with OGA promotes formation of the GlcNAc-cleaved probe, CM-Rhod-P, and a consequent increase in the intensity of fluorescence associated with free CM. Also, it was found that exposure of the probe to phosphatase produces a dephosphorylated probe, βGlcNAc-CM-Rhod, which displays strong fluorescence arising from free Rhod. On the other hand, when incubated with both OGA and phosphatase, βGlcNAc-CM-Rhod-P was converted to CM-Rhod which lacked both βGlcNAc and phosphoryl groups, in conjunction with increases in the intensities of fluorescence arising from both free CM and Rhod. This probe was employed to detect activities of OGA and phosphatase in cell lysates and to fluorescently image both enzymes in cells. Collectively, the findings indicate that βGlcNAc-CM-Rhod-P can be utilized as a chemical tool to simultaneously determine activities of OGA and phosphatase.


Approximating gene transcription dynamics using steady-state formulas.
Understanding how genes in a single cell respond to dynamically changing signals has been a central question in stochastic gene transcription research. Recent studies have generated massive steady-state or snapshot mRNA distribution data of individual cells, and inferred a large spectrum of kinetic transcription parameters under varying conditions. However, there have been few algorithms to convert these static data into the temporal variation of kinetic rates. Real-time imaging has been developed to monitor stochastic transcription processes at the single-cell level, but the immense technicality has prevented its application to most endogenous loci in mammalian cells. In this article, we introduced a stochastic gene transcription model with variable kinetic rates induced by unstable cellular conditions. We approximated the transcription dynamics using easily obtained steady-state formulas in the model. We tested the approximation against experimental data in both prokaryotic and eukaryotic cells and further solidified the conditions that guarantee the robustness of the method. The method can be easily implemented to provide convenient tools for quantifying dynamic kinetics and mechanisms underlying the widespread static transcription data, and may shed a light on circumventing the limitation of current bursting data on transcriptional real-time imaging.


Characterising the costs of the Global Polio Laboratory Network: a survey-based analysis.
To characterise the costs, including for environmental surveillance (ES), of the Global Polio Laboratory Network (GPLN) that provides laboratory support to the Global Polio Eradication Initiative (GPEI). We conducted a survey of the network across 92 countries of the 146 GPLN laboratories plus three non-GPLN laboratories that concentrate environmental samples to collect information about their activities, characteristics and costs during 2016. We estimate the total costs using regression of reported responses and complementing the findings with GPEI data. We received responses from 132 (89%) of the 149 laboratories, with variable response rates for individual questions. We estimate that processing samples of patients with acute flaccid paralysis leads to total costs of approximately $28 million per year (2016 US$) based on extrapolation from reported costs of $16 million, of which 61% were supported by internal (national) funds. Fifty-nine (45%) of the 132 responding laboratories reported supporting ES and we estimate an additional $5.3 million of recurring costs for ES activities performed by the laboratories. The reported costs do not include an estimated additional $10 million of annual global and regional costs to coordinate and support the GPLN. On average, the staff supported by funding for polio in the responding laboratories spent 30% of their time on non-polio activities. We estimate total costs for laboratory support of approximately $43 million (note that this estimate does not include any field or other non-laboratory costs of polio surveillance). Although countries contribute significantly to the GPLN financing, many laboratories currently depend on GPEI funds, and these laboratories also support the laboratory component of surveillance activities for other diseases. Sustaining critical global surveillance for polioviruses and transitioning support for other disease programmes will require continued significant funding after polio certification.


Anal carcinomas: new combined modality treatment approaches.
In the past, anal cancers were treated by abdominal-perineal resection with permanent colostomy. Radiotherapy was used only for inoperable patients or those with unresectable cancers. With improvements in the delivery of radiation, external radiotherapy, brachytherapy, or combinations of the two were used in patients with localized disease of less than 4 cm in size with results similar to surgical resection. Unfortunately, up to 25% of these patients developed severe necrosis necessitating permanent colostomy. During the past decade a considerable change in the treatment of these cancers occurred. Chemo-radiotherapy has made surgical resection unnecessary in the majority of patients. The primary treatment is now the combination of mitomycin-C and 5-fluorouracil (96-hour infusion), plus radiation (3,000 cGy).


Single Nucleotide Polymorphisms and Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis of the Literature.
Meta-analysis. To determine the single nucleotide polymorphisms (SNPs) that are related to adult idiopathic scoliosis. Adolescent idiopathic scoliosis (AIS) is considered one of the most prevalent spinal diseases. Even though the cause of AIS is yet to be determined, family history and sex have shown conclusive associations. Multiple studies have indicated that AIS is more prevalent in families where at least one other first-degree relative is similarly affected, indicating a possible genetic etiology to AIS. Articles were collected from 3 different search engines and then processed in 2 stages for final article selection for quantitative analysis. Five different genetic models were represented to show the association between the different SNPs and AIS. The Hardy-Weinberg equilibrium was examined using Fisher exact test, with significance set at P <0.05. The final analysis paper's quality was evaluated using the Newcastle Ottawa Scale. Kappa interrater agreement was calculated to evaluate the agreement between authors. The final analysis comprised 43 publications, 19412 cases, 22005 controls, and 25 distinct genes. LBX1 rs11190870 T>C and MATN-1 SNPs were associated with an increased risk of AIS in one or all of the 5 genetic models. IGF-1 , estrogen receptor alfa, and MTNR1B , SNPs were not associated with AIS in all 5 genetic models. Newcastle Ottawa Scale showed good quality for the selected articles. Cohen k = 0.741 and Kappa interrater agreement of 84% showed that the writers were in strong agreement. There seem to be associations between AIS and genetic SNP. Further larger studies should be conducted to validate the results.


A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy.
Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type.


The role of specific sources of social support on postinjury psychological symptoms.
The role of perceived social support from specific sources (e.g., families, friends, and significant others) on the development of postinjury posttraumatic stress disorder (PTSD) and associated psychological symptoms (e.g., depression and anxiety) remains relatively unexplored. We examined the predictive role of social support from specific sources on psychological symptoms among emergency department (ED) patients following motor vehicle crash (MVC). Research Methods/Design: Sixty-three injured patients (63.5% female; 37 years old on average) with moderately painful complaints were recruited in the EDs of two Level-1 trauma centers within 24 hr post-MVC. In the ED, participants completed surveys of baseline psychological symptoms and perceived social support; follow-up surveys were completed at 90 days postinjury. Most of the sample (84.1%) was discharged home from the ED with predominantly mild injuries and did not require hospitalization. After adjusting for race, sex, age, and baseline symptoms, hierarchical regression analyses demonstrated that lower perceived social support in the ED predicted higher PTSD symptoms and depressive symptoms (but not anxiety) at 90 days. This effect seemed to be specific to significant others and friends but not family. MVC-related injuries are robust contributors to psychological sequelae. These findings extend prior work by highlighting that perceived social support, particularly from significant others and friends, provides unique information regarding the development of psychological symptoms following predominantly mild MVC-related injuries. This data may serve to inform recovery expectations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib.
We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling. The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics. Proliferation was blocked by all inhibitors in a micro-molar range. With respect to cell kill, dasatinib was most effective, while SU6656 showed moderate and PP2 minor effects. Cellular signaling was affected differently, with PP2 having no effect on SFK signaling while dasatinib probably has non-SFK specific effects. Only SU6656 showed clear SFK specific effects on signaling. The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs.


Normative nasalance scores in Chilean adults.
The present study is aimed towards determining and comparing normative nasalance scores in Chilean Spanish-speaking adult men and women. 40 women (age range 18 to 35, X = 25.79, SD = 5.83) and 36 men (age range 18 to 35, X = 26.45, SD = 4.08) were invited to participate, all of them without any previous speech therapy, neurological pathologies, intellectual deficits, hearing loss, syndromes, or other diagnosed pathologies that could impact speech production.A study of proper velopharyngeal function was performed, using a perceptual resonance evaluation. Nasalance was determined using a model 6450 Nasometer, during the reading of three standardized speech samples in Spanish: a nasal passage (NP), an oronasal passage (ONP), and an oral passage (OP). Also, the nasalance distance was calculated. Genders were compared using Wilcoxon tests for independent samples. The NP presented the highest percentage of nasalance, with 52.13% (± 4.73), followed by the ONP with 25.38% (± 3.7), and finally the OP, which presented the lowest value of 14.15% (± 5.03). Meanwhile, nasalance distance was 37.98% (± 5.32). Finally, no significant differences were observed when comparing the nasalance between genders (p >0.05). The nasalance values obtained were similar to those observed for other Spanish speakers. Also, male and women showed similar scores. The results of this study are a contribution to the indirect assessment of velopharyngeal function in Chilean adults.


Incidence and characteristics of motor vehicle collision-related blunt thoracic aortic injury according to age.
Motor vehicle collision-related blunt thoracic aorta injury (BAI) is rare and highly lethal. Vascular disease as related to advancing age potentially subjects older adults to increased risk of BAI; the mechanisms associated with such injuries may be different as compared with younger adults. The goal of the present study is to test this hypothesis using population-based data. The 1995 to 1999 National Automotive Sampling System data files were used. The National Automotive Sampling System is a national probability sample of passenger vehicles involved in police-reported tow-away crashes. BAI was defined according to the Abbreviated Injury Scale codes. Among those with BAI, information on occupant (age, seating position, restraint use), collision (collision type, delta-V, vehicle intrusion), and outcome characteristics were obtained and compared according to age. The overall incidence of BAI was 6.8 per 10,000 occupants and there was a steady increase in the BAI rate for advancing decades of life. The proportion of occupants with BAI who die at the scene of the collision is relatively consistent across all age groups ( approximately 85%). Among those who survive to receive medical care, ultimate survival is lowest among those aged 60 and older. Near-side collisions were responsible for more BAI among older adults than other age groups (50% vs. 20.6%, p < or = 0.05). Older adults sustained BAI in collisions with lower delta-V values compared with younger persons (p < or = 0.05). Older adults have the highest rate of motor vehicle collision-related BAI, and their injuries tend to occur in less severe collisions. A high level of suspicion for BAI among older adults should not be reserved for high-energy collisions only.


Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy.
A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (-5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.


Theoretical analysis predicts that respiratory sinus arrhythmia does not accurately measure efferent vagal activity during anesthesia.
The respiratory sinus arrhythmia (RSA) is an oscillation of cardiac cycle length (CCL) at the frequency of breathing. RSA is a non-invasive measure of efferent vagal activity, during controlled experimental conditions. Our goal is to assess whether existing theory predicts that RSA amplitude reliably measures efferent vagal activity during and after anesthesia. To do so we combine several existing mathematical models to predict the respiratory sinus arrhythmia. Computer simulation shows that for positive-pressure ventilation without spontaneous breathing efforts, increasing mean arterial pressure causes increase in efferent vagal activity, but not RSA amplitude. Therefore, for positive-pressure ventilation, RSA amplitude does not predict efferent vagal effects on CCL. In contrast, for spontaneous breathing, increasing mean arterial pressure causes increase in both efferent vagal activity and RSA amplitude. Therefore, during spontaneous breathing, RSA amplitude does predict efferent vagal activity. Nevertheless, RSA amplitude also depends on factors that have little effect on efferent vagal activity. For example, RSA amplitude is decreased by increasing respiratory rate or administering acetylcholinesterase and muscarinic antagonists. We conclude that current theory provides little or no justification for using RSA amplitude as a surrogate for efferent vagal activity during anesthesia.


Effects of source and concentration of thrombin, and divalent cations, on thrombin time of heparinized plasma.
The effects of the source and concentration of thrombin, and those of divalent cations, on the thrombin time (TT) of heparinized plasma were investigated. A correlation between TT and the heparin concentration was obtained only when the thrombin was of human origin and when it was reconstituted in divalent cation solutions. Relatively small variations in thrombin concentration resulted in marked differences in TT of heparinized plasma. Bovine thrombin gave a very prolonged TT of heparinized plasma compared with human thrombin, though the two thrombins gave identical TT's for non-heparinized control plasma. Divalent cation solution, in which thrombin was reconstituted, had a profound influence on TT of heparin plasma. When thrombin was reconstituted in 0.1 M MnCl2 solution, the TT of a plasma containing 0.5 unit heparin per ml. was the same as that of a plasma containing no heparin. The reliability of the thrombin time test as a means of monitoring heparin anticoagulation must be established by individual laboratories via extensive testing of clinical samples.


Fetus in fetu.
Fetus in fetu occurs due to aberration of monozygotic twinning. A 16-year-old boy presented with abdominal pain and mass. Laparotomy revealed an anencephalic fetus within an encapsulated retroperitoneal mass. Pathologic examination confirmed rib formation with a primitive vertebral column with bone marrow. There was no other organogenesis.


Is there significant improvement in neonatal outcome after treating pPROM mothers with amnio-infusion?
The aim of this study was to determine the effects of amnio-infusion treatment on fetal and neonatal mortality and neonatal pulmonary development in women with singleton pregnancies and premature rupture of the membranes occurring at a gestational age of <26 weeks and who had severe oligohydramnios. The treated group of 45 consenting women received serial amnio-infusion and was compared with the control group of 44 women who underwent waiting treatment. Our study confirmed a higher number of live births in the treated group, especially in cases with a gestational age at rupture (GAR) of <20 weeks. Furthermore, even if GAR is an important factor for predicting pulmonary hypoplasia, amnio-infusion treatment reduces the probability of pulmonary hypoplasia. In fact, over 20 weeks, amnio-infusion treatment significantly reduces the risk of pulmonary hypoplasia even if normal lung development cannot be guaranteed.


Influence of Optic Disc Size on Identifying Glaucomatous Optic Neuropathy.
The aim of this study was to use a large group of observers to test prior research findings that suggest optic disc size, clinical evaluation of the neuroretinal rim (ISNT rule), and practitioner characteristics influence the accuracy of differentiating normal from glaucomatous optic nerves. Participant observers were optometrists, optometry students, and vision scientists/researchers attending the 2013 American Academy of Optometry Annual Meeting. Each observer viewed and judged six sets of stereoscopic photographs of normal and clinically confirmed glaucomatous optic nerves of different sizes presented in random order. Observers were queried on whether each nerve was glaucomatous or normal, whether the nerve followed the ISNT rule, and whether further evaluation with advanced imaging techniques was indicated. Of the 261 observers who participated, 59% were practicing optometrists, 7% were vision scientists, and 34% were residents or students. Of practicing optometrists and vision scientists, half (49%) had more than 15 years of experience, whereas 11% had less than 2 years of experience. Diagnostic accuracy differed based on optic nerve size: average-sized nerves were correctly identified by 90% of subjects, whereas small nerves and large nerves were correctly identified by 42% and 62%, respectively. Notably, only 9% of subjects correctly identified the small glaucomatous nerve, and only 34% correctly identified the large normal nerve. No practitioner characteristics were associated with diagnostic accuracy. Accurate identification of glaucomatous optic neuropathy was significantly influenced by optic disc size. This was particularly evident for the large normal nerve and the small glaucomatous nerve. The ISNT rule provided value for differentiating normal from glaucomatous nerves, but its subjective interpretation resulted in considerable intergrader variability. These findings agree with other studies utilizing smaller numbers of observers but larger numbers of optic nerve presentations that disc size and the ISNT rule have value for enhancing accuracy of optic nerve assessment.


[Case of postoperative pulmonary embolism after tonsillectomy in a healthy young woman].
An 18-year-old healthy woman with no previous history of coagulation disorders underwent general anesthesia for tonsillectomy. The procedure was uneventful. After the surgery, she was ordered to rest on bed overnight. The next day, the patient experienced transient syncope followed by hypotension (< 60 mmHg) and severe dyspnea. Epinephrine 2 mg administration restored the blood pressure promptly, yet dyspnea persisted. The lung-perfusion scintigraphy showed upper-lobe perfusion defect in the left lung and she was diagnosed as having pulmonary embolism. She received low-molecular-weight heparin and warfarin therapy and recovered fully. The postoperative laboratory analysis did not show thrombophilic disorders or prothrombotic state. The pulmonary embolism was speculated to have occurred due to deep vein thrombosis which developed after postoperative immobilization. The prophylactic maneuvers such as elastic stockings were not applied to the patient preoperatively, who had been considered unlikely to develop deep vein thrombosis. Although deep vein thrombosis in children and adolescence are rare, postoperative children should be monitored carefully for thrombotic complications. Postoperative bed rest should be minimized in terms of prevention of thrombosis.


Which nurseries currently care for ventilated neonates in Illinois and Wisconsin? Implications for the next generation of perinatal regionalization.
We were interested in the extent to which advances in the availability of neonatalogy expertise have provided a centrifugal impetus to perinatal care. Specifically, we wondered where infants who were sick enough to require mechanical ventilation were currently being managed. We surveyed 116 of 140 hospitals in Illinois and Wisconsin that offered obstetric/newborn services in 1998-1999. The 23 Level I nurseries were consistently small, and offered virtually no "advanced" neonatal intensive care unit (NICU) technology. The 16 Level III NICUs were consistently large, offered advanced technology and personnel, and received sick infants from many hospitals in their regional network. The 77 Level II nurseries (two thirds of all hospitals with newborn services) were less consistently characterized. In general, Level II nurseries were a "spoke" (not a hub), and did not offer extracorporeal-membrane oxygenation (ECMO), nitric oxide (NO), or cardiovascular (CV) surgery. However, 19 (25%) of 77 Level II centers self-designated as "Level II+". These were significantly more likely to offer ventilators, percutaneous central venous catheters (PCVCs), total parenteral nutrition (TPN), and surgery. Fifty-three percent (18/34) of all nurseries offering mechanical ventilation self-designated as a Level II or II+, as opposed to Level III. Facile inferences about the appropriate role of Level II centers derived from decades-old data are probably unsupportable. It is time to acknowledge the distinction between the Level II nursery of the past and the newly evolving Level II+ NICUs.


Clinical and regulatory development strategies for Shigella vaccines intended for children younger than 5 years in low-income and middle-income countries.
Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in low-income and middle-income countries (LMICs). Several Shigella vaccine candidates are advancing in clinical trials and offer promise. Although multiple target populations might benefit from a Shigella vaccine, the primary strategic goal of WHO is to accelerate the development and accessibility of safe, effective, and affordable Shigella vaccines that reduce mortality and morbidity in children younger than 5 years living in LMICs. WHO consulted with regulators and policy makers at national, regional, and global levels to evaluate pathways that could accelerate regulatory approval in this priority population. Special consideration was given to surrogate efficacy biomarkers, the role of controlled human infection models, and the establishment of correlates of protection. A field efficacy study in children younger than 5 years in LMICs is needed to ensure introduction in this priority population.


Prolongation of gestation by growth hormone: a confounding factor in the assessment of its prenatal action.
The administration of urified growth hormone to normally nourished pregnant rats prolonged gestation leading to postmaturity of the offspring. The effect explains, in part, the apparent influence of growth hormone on prenatal and early postnatal development and supports the notion that the prenatal action of exogeneous growth hormone is restricted to a therapeutic one under conditions of malnutrition.


Overexpression of neuroserpin in larval and adult zebrafish shows different behavioral phenotypes.
Serpini1, which encodes neuroserpin, has been implicated in the development and maintenance of the nervous system. In this study, an inducible neuroserpin overexpression transgenic zebrafish was generated to investigate its role in different developmental stages. Neuroserpin overexpression was induced by doxycycline in larval and adult zebrafish respectively. Locomotion and thigmotaxis were recorded and analyzed using the ZebraBox high-throughput monitoring equipment and the ZebraLab software system. We find that Tg (serpini1) (+DOX) zebrafish larvae are more hypoactive than their wild-type counterparts at 7 day-postfertilization and anxiety-like behavior is observed in Tg (serpini1) (+DOX) adult zebrafish at 3 month-postfertilization. Furthermore, RNA-sequencing analysis reveals that neuroserpin overexpression affects neurodegeneration-related gene expression. In summary, we report that neuroserpin overexpression in larval and adult zebrafish shows different behavioral phenotypes.


Immunophenotype of neutrophils in oral squamous cell carcinoma patients.
The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data. Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1β was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant. Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died. The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator.


The pediatric outcomes data collection instrument detects improvements for children with ambulatory cerebral palsy after orthopaedic intervention.
The purpose of this study was to assess whether the Pediatric Outcomes Data Collection Instrument (PODCI) was able to detect changes in function, as perceived by the parents of children and adolescents with cerebral palsy who had undergone lower limb soft tissue and/or bony surgeries. This was a retrospective study of 80 ambulatory patients who were seen in the motion laboratory and classified with the Gross Motor Functional Classification System (GMFCS). Significant changes (P < 0.05) were detected in the PODCI scores for upper extremity function, transfers and mobility, physical function and sports, and global function after surgery, by approximately 4% to 5%, whereas comfort (pain-free) did not significantly change. There was a significant difference in the PODCI scores preoperatively between GMFCS levels I, II, and III for upper extremity function, transfers and mobility, physical function and sports, and global function. Postoperative improvements were of equal magnitude for each GMFCS level. This suggests that the PODCI did not have a ceiling effect for high-functioning children. Age (+/-10 years) and surgery (soft tissue/soft tissue plus bony) were not significant factors for any of the subcategories preoperative to postoperative. In conclusion, the PODCI detected improvement as perceived by the parents in ambulatory children with cerebral palsy after lower-limb soft tissue and/or bony surgeries in 4 areas by a magnitude of approximately 4% to 5%.


K-13, a novel inhibitor of angiotensin I converting enzyme produced by Micromonospora halophytica subsp. exilisia. I. Fermentation, isolation and biological properties.
A novel inhibitor of angiotensin I converting enzyme (ACE), designated K-13, was isolated from the culture broth of Micromonospora halophytica subsp. exilisia K-13. K-13 inhibited ACE non-competitively when hippuryl-L-histidyl-L-leucine was used as a substrate. The inhibition constant (Ki) was 0.349 microM. K-13 hardly inhibited carboxypeptidase A, trypsin, alpha-chymotrypsin, leucine aminopeptidase, and aminopeptidase B even at a level of 61 microM. When K-13 was administered intravenously to rats, it inhibited the pressor response to angiotensin I.


An enzyme-linked immunosorbent assay (ELISA) to measure growth hormone level in serum and milk of buffaloes (Bubalus bubalis).
An indirect Sandwich ELISA to measure growth hormone level in serum and milk of buffaloes was developed. The assay was based on purified anti rbST IgG raised in rabbits and chicken and rabbit anti chicken IgG horseradish peroxidase. The assay was validated in terms of sensitivity, specificity, precision and recovery. Parallelism was demonstrated between the standard curve and serially diluted serum, milk and pituitary derived growth hormone. Sensitivity of the assay was 0.1 ng/ml. Recovery of exogenous bovine somatotropin from serum and milk ranged from 90 to 102% and 96 to 108% respectively. The intra and inter assay variations to measure growth hormone in serum and milk were 3.36 to 8.81% and 6.01 to 12.31% respectively. Statistical analysis for parallelism and cross-reactivity of rbST with serum of other species confirmed the reproducibility of the assay.


Regulation of alpha 4 integrin-mediated adhesion of human eosinophils to fibronectin and vascular cell adhesion molecule-1.
Eosinophils selectively accumulate at sites of allergic inflammation. Their recruitment is dependent on both the expression and functional activity of cell adhesion molecules. How the functional activity of cell adhesion molecules on eosinophils is regulated is poorly understood. Our objective was to examine the functional activity of alpha 4 integrins on human eosinophils and its regulation by various agents. Function of alpha 4 integrins on human eosinophils was examined by testing adhesion to immobilized fibronection and vascular cell adhesion molecule-1 (VCAM-1) in the presence or absence of a monoclonal antibody (mAb) (8A2) that activates beta 1 integrin function. Spontaneous eosinophil adhesion to VCAM-1 was enhanced by 8A2, but adhesion to fibronectin could only be detected in the presence of 8A2. Concentrations of 8A2 that were approximately 100-fold less than saturating induced maximal eosinophil adhesion. Adhesion to VCAM-1 in the presence of 8A2 was effectively inhibited by alpha 4 and beta 1 integrin mAbs: beta 7 mAb had partial inhibitory activity. Connecting segment-1 peptide and alpha 4 mAb blocked 8A2-dependent fibronectin binding: beta 1, beta 2, and beta 7 integrin mAbs had partial inhibitory activity. Eosinophils obtained from bronchoalveolar lavage fluids and blood eosinophils stimulated with IL-5, platelet-activating factor, or RANTES displayed increased beta 2 integrin-dependent, not alpha 4 integrin-dependent, attachment. Spontaneous adhesion of eosinophils to VCAM-1 was significantly reduced by the tyrosine kinase inhibitor tyrphostin B46 (inhibitory concentration of 50% approximately equal to 20 mumol/L); this effect was reversed by 8A2. The functional activity of integrins on eosinophils can be positively and negatively regulated. Altered integrin avidity may influence eosinophil recruitment in vivo.


Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma.
Macrophages constitute a major immune component in tumor tissues, but how these cells adapt to and survive in the nutrient-depleted and lactic acid-induced acidic tumor microenvironments is not yet fully understood. Here, we found that levels of carbonic anhydrase XII (CA12) expression were significantly and selectively upregulated on macrophages in human hepatocellular carcinoma (HCC). Transient glycolytic activation of peritumoral monocytes induced sustained expression of CA12 on tumor-infiltrating macrophages via autocrine cytokines and HIF1α pathways. On the one hand, CA12 mediated the survival of macrophages in relatively acidic tumor microenvironments, while on the other hand, it induced macrophage production of large amounts of C-C motif chemokine ligand 8 (CCL8), which enhanced cancer cell epithelial-mesenchymal transition (EMT) and facilitated tumor metastasis. Consistently, the accumulation of CA12+ macrophages in tumor tissues was associated with increased tumor metastatic potential and reduced survival of patients with HCC. Selective targeting of tumor-infiltrating macrophages with a CA12 inhibitor reduced tumor growth in mice and was sufficient to synergistically enhance the therapeutic efficacy of immune-checkpoint blockade. We suggest that CA12 activity is a previously unappreciated mechanism regulating the accumulation and functions of macrophages in tumor microenvironments and therefore represents a selective vulnerability that could be exploited in future designs for antitumor immunotherapeutic strategies.


Genistein.
Genistein (4',5,7-trihydroxyisoflavone) is a common precursor in the biosynthesis of antimicrobial phytoalexins and phytoanticipins in legumes, and an important nutraceutical molecule found in soybean seeds. Genistein is a phytoestrogen with a wide variety of pharmacological effects in animal cells, including tyrosine kinase inhibition, and dietary genistein ingestion has been linked, through epidemiological and animal model studies, with a range of potential health beneficial effects. These include chemoprevention of breast and prostate cancers, cardiovascular disease and post-menopausal ailments. In spite of an extensive literature on the effects of dietary genistein, questions still exist as to its potential overall benefits as a component of the human diet. Genistein can be synthesized chemically via the deoxybenzoin or chalcone route. Genistein is synthesized in plants from the flavanone naringenin by a novel ring migration reaction catalyzed by the cytochrome P450 enzyme isoflavone synthase (IFS). IFS genes have recently been cloned from a number of plant species, and production of genistein can be now achieved in non-legumes by recombinant DNA approaches.


Save it-don't waste it! Maximizing utilization of erythrocytes from previously stored whole blood.
Recent military and civilian experience suggests that fresh whole blood may be the preferred for treatment of hemorrhagic shock, but its use is limited by its 21-day shelf life. The red blood cell storage lesion and coagulation status of packed red blood cells (pRBCs) salvaged from expired whole blood are unknown. We hypothesized that pRBCs can be salvaged from previously stored whole blood. Cold stored, low-titer, O-positive, nonleukoreduced, whole blood units were obtained at 21 days of storage. Erythrocytes were separated by centrifugation, resuspended in AS-3, and stored for 21 additional days as salvaged pRBCs. The red blood cell storage lesion parameters of microvesicles, Band-3, free hemoglobin, annexin V, and erythrocyte osmotic fragility were measured and compared with pRBCs prepared at the time of donation and stored in AS-3 for 42 days (standard pRBCs). In additional experiments, murine pRBCs were prepared from expired whole blood units and compared with those stored under standard conditions. Mice underwent hemorrhage and resuscitation with standard and salvaged pRBC units, and serum cytokines and free hemoglobin were determined. There were no significant differences in microvesicle formation or cell-free hemoglobin concentration between salvaged and standard pRBCs. There was decreased Band-3 and increased phosphatidylserine in the salvaged units as well as greater osmotic fragility. Salvaged pRBCs maintained consistent clot firmness. After hemorrhage and resuscitation in a murine model, salvaged pRBCs did not demonstrate increased serum cytokine levels. Salvaged pRBCs from previously stored whole blood accumulate the red blood cell storage lesion in a similar fashion to standard pRBCs and maintain consistent coagulability when reconstituted with plasma. Salvaged pRBCs are not associated with an increased inflammatory response when used for resuscitation in a murine model. Salvaged pRBCs may be a viable product for utilization in the treatment of traumatic hemorrhagic shock.


Dihydroergotamine in prevention of infusion thrombophlebitis. A randomized trial.
The efficiency of subcutaneous dihydroergotamine in preventing infusion thrombophlebitis was assessed in a randomized trial. One hundred and fourteen postoperative patients were studied. They furnished a total of 160 infusion sites. The difference between treatment and control group with regard to incidence of infusion thrombophlebitis was not significant (p greater than 0.05). Accordingly dihydroergotamine has no substantial effect.


Mono and diterpene production in Escherichia coli.
Mono- and diterpenoids are of great industrial and medical value as specialty chemicals and pharmaceuticals. Production of these compounds in microbial hosts, such as Escherichia coli, can be limited by intracellular levels of the polyprenyl diphosphate precursors, geranyl diphosphate (GPP), and geranylgeranyl diphosphate (GGPP). To alleviate this limitation, we constructed synthetic operons that express three key enzymes for biosynthesis of these precursors: (1). DXS,1-deoxy-d-xylulose-5-phosphate synthase; (2). IPPHp, IPP isomerase from Haematococcus pluvialis; and (3). one of two variants of IspA, FPP synthase that produces either GPP or GGPP. The reporter plasmids pAC-LYC and pACYC-IB, which encode enzymes that convert either FPP or GGPP, respectively, to the pigment lycopene, were used to demonstrate that at full induction, the operon encoding the wild-type FPP synthase and mutant GGPP synthase produced similar levels of lycopene. To synthesize di- or monoterpenes in E. coli using the GGPP and GPP encoding operons either a diterpene cyclase [casbene cyclase (Ricinus communis L) and ent-kaurene cyclase (Phaeosphaeria sp. L487)] or a monoterpene cyclase [3-carene cyclase (Picea abies)] was coexpressed with their respective precursor production operon. Analysis of culture extracts or headspace by gas chromatography-mass spectrometry confirmed the in vivo production of the diterpenes casbene, kaur-15-ene, and kaur-16-ene and the monoterpenes alpha-pinene, myrcene, sabinene, 3-carene, alpha-terpinene, limonene, beta-phellandrene, alpha-terpinene, and terpinolene. Construction and functional expression of GGPP and GPP operons provides an in vivo precursor platform host for the future engineering of di- and monoterpene cyclases and the overproduction of terpenes in bacteria.


Prognostic implications of combined prone and supine acquisitions in patients with equivocal or abnormal supine myocardial perfusion SPECT.
Although acquisition of (99m)Tc-sestamibi myocardial perfusion SPECT (MPS) with the patient in the prone position is commonly used to minimize attenuation artifacts, the impact of combined prone and supine imaging on the prognostic evaluation of coronary artery disease (CAD) has not been determined. The prognostic implications of MPS obtained in both prone and supine positions in patients with perfusion defects on supine MPS were evaluated. We studied 3,834 patients who were monitored for 24.2 +/- 6.0 mo after rest (201)Tl/stress (99m)Tc-sestamibi MPS acquired during 1994-1995, when prone acquisition was performed only in patients with inferior wall perfusion defects that might represent attenuation or motion artifact. During follow-up, there were 132 hard events (cardiac death or myocardial infarction) and 375 total events (hard events or late myocardial revascularization). Overall, patients who underwent prone and supine acquisitions had similar characteristics to those who underwent supine-only imaging, with the exception of being more commonly male. In multivariable analysis, there were similar independent predictors for hard events and total events; the type of acquisition (prone and supine or supine-only) was not a significant predictor of either of these outcome events. After risk adjustment, the predicted event rates were nearly identical for patients undergoing prone and supine compared with supine-only studies. Both observed and predicted hard event rates of patients with normal prone and supine versus supine-only imaging were very low (observed, 0.7%/y and 0.5%/y, respectively; predicted, 1.5% over 24 mo for both). There was no reduction in the higher rates of events associated with abnormal scan results with the combination of prone and supine imaging. Patients with inferior wall defects on supine MPS that are not present on prone MPS have a low risk of subsequent cardiac events, similar to that of patients with normal supine-only studies.


High bone density in adolescents with obesity is related to fat mass and serum leptin concentrations.
Obesity has been associated with increased bone mass, but the mechanisms involved are still poorly understood. We aimed to explore the relation between bone mineral density and factors known to influence bone formation in obese and lean adolescents. We recruited 24 obese and 25 lean adolescents in a case-control study. Total body bone mineral density (TB-BMD) z scores and body composition were determined using dual-energy x-ray absorptiometry. We measured 25-hydroxyvitamin D (25-OH-D), glucose, insulin, and leptin concentrations. Physical activity (PA) level was quantified using accelerometer. TB-BMD z score was higher, whereas 25-OH-D and PA levels were lower in obese compared with lean subjects (TB-BMD z score 1.06 ± 0.96 vs 0.26 ± 0.91, P = 0.004; 25-OH-D 9.9 ± 6.4 vs 18.5 ± 7.4 ng mL, P < 0.001; PA level 308.3 ± 22.1 vs 406.8 ± 29.2 count min, P = 0.01). TB-BMD z score was not related to 25-OH-D or PA levels, but was positively correlated with leptin concentration and fat mass (P < 0.05). Vitamin D concentration was negatively correlated with fat mass (P < 0.001). Despite lower serum vitamin D and PA levels, BMD was higher in adolescents with obesity and associated with higher serum leptin concentrations. Furthermore, adolescents with obesity have lower vitamin D serum concentrations than lean controls, probably owing to its distribution in adipose tissue.


A comprehensive prognostic and immunological analysis of telomere-related lncRNAs in kidney renal clear cell carcinoma.
Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignant tumors of the urinary system, with a high recurrence and metastasis rate. Telomeres and long non-coding RNAs (lncRNAs) have been documented playing critical roles in cancer progression. However, the prognostic significance of telomere-related lncRNA (TRLs) in KIRC is less well-defined. The Cancer Genome Atlas database was applied to retrieve the expression profiles and corresponding clinical information of KIRC patients. To create the TRLs prognostic signature, univariate Cox regression, least absolute shrinkage and selection operator analyses were performed. The prognostic signature, comprised of nine prognostic TRLs, was developed and demonstrated superior prognostic ability for KIRC patients. Additionally, the risk score acted as an independent prognostic indicator. A nomogram incorporating age, grade, stage, and signature-based risk scores was also developed and exhibited excellent predictive accuracy. Several immune activities were associated with the signature, as determined by gene function analysis. Further analysis revealed differences in the status of immunity and the tumor microenvironment between low- and high-risk groups. Notably, KIRC patients with high-risk scores were more responsive to immunotherapy and chemotherapy. To summarize, our study developed a new prognostic signature consisting of nine telomere-related lncRNA that can precisely predict the prognosis of KIRC patients. The signature was shown to be of substantial value for the tumor microenvironment and tumor mutation burden, thereby contributing to a framework for the individualized treatment of patients.


Primary Retroperitoneal Teratoma with Predominant Neurogenic Elements Masquerading as Adrenal Tumor.
Primary retroperitoneal teratomas are uncommon extragonadal nonseminomatous germ cell tumors that are composed of well differentiated parenchymal tissues which are derived from more than one of the three embryonic germ cell layers. Here we report an unusual and first of its kind, a case of primary mature cystic retroperitoneal teratoma mimicking as adrenal tumor in a 7-month-old female in which the tumor was predominantly composed of neurogenic tissue histologically which is unlike the usual pattern seen in the teratomas.


Rural Nurses' Views on Breastmilk Banking in Limpopo Province, South Africa: A Qualitative Study.
The development of breastmilk banks is being established among the African population, including in Limpopo Province. However, the views of nurses directly handling the donated breastmilk in the province remain unknown. This study was aimed at exploring and describing the views of nurses towards breastmilk banking in the Mankweng area, Limpopo Province. A qualitative, descriptive, and explorative study was undertaken at a tertiary hospital and a rural feeder clinic in the Mankweng area. Purposive sampling was employed to obtain participants for the interviews. One-on-one, semi-structured interviews were conducted to explore the views of these nurses. Data were analysed using Tesch's open coding method, with the information obtained being grouped into different themes and sub-themes. Almost all nurses were willing to donate their breastmilk to the bank. However, receiving donated breastmilk for their own children seemed to be a challenge due to the safety of the donated breastmilk, uncertainty about the screening process, and cultural issues. Although donation of breastmilk appeared to be well supported by almost all the nurses, the use of donated breastmilk seemed to be not fully acceptable. Increased awareness about breastmilk donation and banking should be prioritised in the province.


Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA.
Background: The combination of clopidogrel and aspirin is recommended for the treatment of patients with acute minor stroke or transient ischemic attack (TIA). However, with varied clopidogrel resistance (often due to CYP2C19 loss-of-function (LOF) alleles), alternatives like ticagrelor have been suggested. Previous studies showed that ticagrelor had a lower platelet reactivity assessed by VerifyNow P2Y12 assay than clopidogrel. We aimed to compare the effect of ticagrelor vs. clopidogrel on platelet reactivity assessed by a different method (Aggrestar platelet function analyzer) and analyze whether CYP2C19 genotypes were involved. Methods: A pre-specified subgroup analysis of a randomized controlled trial- Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by Aggrestar (PL) platelet function analyzer and high on-treatment platelet reactivity (HOPR) on ticagrelor or clopidogrel was compared. Clinical outcomes included any stroke, composite vascular events and bleeding events within 90 days. Patients were categorized into carriers and non-carriers according to the carrier status of CYP2C19 LOF alleles. Results: Among 675 patients enrolled in the PRINCE trial, 387 patients were included in this subgroup: 197 were randomized to ticagrelor plus aspirin and 190 to clopidogrel plus aspirin. At 90 ± 7 days, compared with clopidogrel/aspirin group, the proportion of HOPR in ticagrelor/aspirin group was significantly lower (19.6 vs. 40.8%, P < 0.001). No significant treatment-by-genotype interactions were found (P for interaction = 0.12). Within 90 days, a trend toward a lower risk of new stroke in ticagrelor/aspirin compared to clopidogrel/aspirin was observed (4.6 vs. 9.5%, HR 0.47, 95% CI 0.21-1.05, P = 0.06). Conclusions: Ticagrelor is superior to clopidogrel in inhibiting platelet reactivity measured by the PL platelet function analyzer among patients with acute minor stroke or TIA. Our study confirmed the finding of the main analysis of PRINCE trial in a different assay. Large randomized controlled trials are needed to evaluate our findings. Clinical Trial Registration: Clinicaltrials.gov NCT02506140.


Fatal fulminant hypereosinophilic syndrome with a petechial rash in a 16-year-old girl.
Peripheral blood eosinophilia and eosinophilic tissue infiltration characterize the hypereosinophilic syndrome, which if untreated can be fatal. Its manifestations are protean. Often a diagnosis of exclusion, it presents diagnostic challenges. A fatal case of hypereosinophilic syndrome in a 16-year-old girl with petechiae, edema, urticaria, and diffuse erythema unfolded over 2 weeks. The histopathology of the petechiae demonstrated an eosinophilic and mixed cell interstitial and perivascular infiltrate and microthrombi in vessels. There was no evidence of T-cell clonality. Despite treatment with cyclosporine and methylprednisolone, she died. The age group; fulminant, fatal course without neoplasia; striking eosinophilia; and petechial rash are notable.


Prostatic stents and balloon dilatation.
Prostatic obstruction of urinary flow is a common age-related event resulting in both troublesome symptoms and retention of urine. There have been recent developments in the management of such patients by inserting metallic stents or by balloon dilatation of the prostatic urethra. The role of these treatments as alternatives to surgery is evaluated and some of the difficulties encountered in their usage are described in this article.


Neutrophil oxygen metabolite inhibition of cultured chinchilla middle ear epithelial cell growth.
Middle ear inflammation in acute bacterial otitis media is characterized by accumulation of neutrophils in middle ear effusion. Since neutrophils release products that may injure surrounding tissues, we studied the effect of neutrophil metabolic products on middle ear epithelial cells (MEECs) in vitro. Chinchilla MEECs were incubated with phorbol myristate acetate (PMA)-activated human neutrophils or with hydrogen peroxide (H2O2). Cell growth, which was measured by 3H-thymidine incorporation, was inhibited by activated neutrophils and by H2O2. Unstimulated neutrophils, PMA alone, and catalase alone did not affect the viability of MEECs. Catalase, an enzyme that reduces H2O2, partially blocked the inhibitory effect of activated neutrophils and completely blocked the inhibitory effect of H2O2. Inhibition of MEEC metabolism by neutrophil-reactive oxygen species may contribute to epithelial injury, which may prolong the middle ear inflammatory response and lead to chronic tissue damage.


Marketplaces, Markets, and Market Design.
Marketplaces are often small parts of large markets, and both markets and marketplaces come in many varieties. Market design seeks to understand what marketplaces must accomplish to enable different kinds of markets. Marketplaces can have varying degrees of success, and there can be marketplace failures. I'll discuss labor markets like the market for new economists, and also markets for new lawyers and doctors that have suffered from the unraveling of appointment dates to well before employment begins. Markets work best if they enjoy social support, but some markets are repugnant in the sense that some people think they should be banned, even though others want to participate in them. Laws banning such markets often contribute to the design of illegal black markets, and this raises new issues for market designers. I'll briefly discuss markets and black markets for narcotics, marijuana, sex, and surrogacy, and the design of markets for kidney transplants, in the face of widespread laws against (and broader repugnance for) compensating organ donors. I conclude with open questions and engineering challenges.


Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study.
Peroxisome proliferator activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily that regulates key proteins involved in fatty acid oxidation, extracellular lipid metabolism, hemostasis, and inflammation. A L162V polymorphism at the PPARA locus has been associated with alterations in lipid and apolipoprotein concentrations. We studied the association among lipids, lipoproteins, and apolipoproteins and the presence of the L162V polymorphism in 2373 participants (1128 men and 1244 women) in the Framingham Offspring Study. The frequency of the less common allele (V162) was 0.069. The V162 allele was associated with increased serum concentrations of total and LDL cholesterol in men (P=0.0012 and P=0.0004, respectively) and apolipoprotein B in men (P=0.009) and women (P=0.03 after adjustment for age, body mass index, smoking, and use of beta-blockers, diuretics or estrogens). Apolipoprotein (apo) C-III concentrations were higher in carriers of the V162 allele. The association of the L162V polymorphism on LDL cholesterol concentration was greatest in those who also carried the E2 allele at the APOE locus and the G allele at the APOC3 3238C>G polymorphism. This suggests that alterations in triglyceride-rich lipoprotein metabolism may be involved in the generation of the increase in LDL cholesterol observed with the L162V PPARA polymorphism.


Clinical outcomes for the obese hospital inpatient: An observational study.
The prevalence of obesity presents a burden for Australian health care. The aim of this study was to determine whether severely obese hospital inpatients have worse outcomes. This is an observational cohort study, using data from all adult patients admitted to hospital for all elective and emergency admissions of patients aged over 18 years to two large Australian urban hospitals. We measured their length of stay, intensive care unit admission rate, intensive care unit length of stay, mortality and readmission rates within 28 days of discharge and compared these outcomes in the severely obese and non-severely obese subjects using t-test or chi-square test as appropriate. Between February 2008 and February 2012, 120,872 were admitted to hospital 193,800 times; 2701 patients were identified as severely obese (2.23%) and 118,171 patients were non-severely obese. If admitted as an emergency, severely obese patients have worse outcomes and consume more resources than other patients. These outcomes are still worse, but less so, if the obese patient is admitted as an elective patient suggesting that anticipation of any obesity-specific problems can have a beneficial effect. Upon admission or discharge of severely obese hospital inpatients, health care plans should be even more carefully laid than usual to reduce the risk of readmission.


Evaluation and Monitoring of Endometrial Cancer Based on Magnetic Resonance Imaging Features of Deep Learning.
This study was aimed to compare and analyze the magnetic resonance imaging (MRI) manifestations and surgical pathological results of endometrial cancer (EC) and to explore the clinical research of MRI in the diagnosis and staging of EC. Methods. 80 patients with EC admitted to the hospital were selected as the research objects. The ResNet network was used to optimize the network. When the depth was added, the accuracy of the model was improved, the network parameters were iteratively updated, and the damage function of the minimized network was obtained. The recognition efficiency of MRI images was analyzed using three network modes: shallow CNN network, Res-Net network, and optimized network. The images of EC patients were analyzed, and a quantitative and timed MRI was achieved using simulated datasets in deep learning neural networks, which provided the basis for the formulation of single-scan MRI parameters. All patients underwent preoperative MRI examination using coronal and sagittal T1WI and T2WI imaging. The results showed that the accuracy and specificity of T2 weighted imaging and enhanced scanning in MRI were 88.75% and 95%, respectively. Sensitivity was 87.5%, negative predictive value was 93.75%, and positive predictive value was 86.25%. By MRI examination, 80 cases of EC in patients with stage I diagnosis were 72 cases, accounting for 90%, with endometrial thickening and uneven enhancement. In conclusion, the MRI manifestations of EC are diversified, and MRI has a high value for the staging of EC. MRI examination is conducive to improving diagnostic accuracy.


[A craniofacial approach to disseminated tumors of the anterior portions of the cranial base].
The authors have developed a modified craniofacial approach. Its essence is to extend a facial cut along the mid-forehead after Weber-Fergusson into the frontoparietotemporal region, by forming a common soft tissue craniofacial graft. The above access was used in 17 patients with benign tumors of the base of the skull, involved into the ethmoidal sinus, anterior cranial fossa, medial portions of one or both eye sockets, sphenoidal sinus, medial portions of one or both maxillary sinuses, nasal cavity, and nasopharynx. The use of this access increases the radical rate of removal of extended craniofacial tumors. The specific policy features of surgery and postoperative management.


Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?
Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.


Effect of sensory experience on motor learning strategy.
It is well known that the central nervous system automatically reduces a mismatch in the visuomotor coordination. Can the underlying learning strategy be modified by environmental factors or a subject's learning experiences? To elucidate this matter, two groups of subjects learned to execute reaching arm movements in environments with task-irrelevant visual cues. However, one group had previous experience of learning these movements using task-relevant visual cues. The results demonstrate that the two groups used different learning strategies for the same visual environment and that the learning strategy was influenced by prior learning experience.


Improvement in renal function and rejection control in pediatric liver transplant recipients with the introduction of sirolimus.
Calcineurin inhibitors have dramatically improved the outcomes of pediatric liver transplantation. However, calcineurin inhibitor use is associated with a 50% reduction in glomerular filtration rate in the first year post-transplant. Nephrotoxicity can be difficult to manage, especially in the pediatric population. We hypothesized that the addition of an mTOR inhibitor with decreased calcineurin inhibitor levels might improve or prevent renal insufficiency and improve control of rejection. A retrospective chart review was performed on the patients treated with sirolimus who had undergone an orthotopic liver transplant between January 2000 and February 2003. Thirty-eight patients were identified. Mean age was 8.6 yr. Fourteen patients were male and 24 were female. Mean weight was 30.3 kg. The most common indications for starting sirolimus were rejection (42%) and renal impairment (29%). Seventy-three percent of patients begun on sirolimus remain on the medication. Those with renal impairment (11 patients) showed improvement in their creatinine levels from a mean baseline of 1.3 to 0.8 mg/dL. Their calculated creatinine clearance (Schwartz formula) improved from 63.7 to 84.8 mL/min (p = 0.03). Patients started on sirolimus for rejection showed significant improvement in hepatocellular enzymes despite a reduction in the tacrolimus level from 12.2 to 7.5 ng/mL. The mean alanine aminotransferase level improved from 221 to 100 units/L (p = 0.02), and the mean aspartate aminotransferase improved from 121 to 99 units/L (p = 0.59). Addition of sirolimus to a tacrolimus-based regimen with lower target tacrolimus levels improved liver function in patients with rejection. Addition of sirolimus significantly improved renal function as shown by creatinine level and calculated creatinine clearance in those children with renal impairment. The effect of combined immunosuppressant treatment with tacrolimus and sirolimus on long-term renal function needs to be evaluated.


Social Capital and Mental Health in Post-Disaster/Conflict Contexts: A Systematic Review.
Social capital (SC) is highlighted as an important factor for post-crisis mental health outcomes. However, the heterogeneous nature of the construct makes it difficult to get a clear picture of the evidence concerning the association between SC indices and mental health. This review examines how SC is conceptualized and measured, and the relationships with other variables in quantitative empirical studies investigating the associations between SC and mental health in post-disaster and post-conflict contexts. It includes primary data studies focusing on this association in civilian populations. Studies were identified by searching electronic databases, bibliographic mining, cited reference searching, and personal contact with experts. In total, 15 studies were included: 12 in post-natural disaster contexts and 3 in conflict-affected settings. Findings suggested that individual cognitive SC had an inverse association with post-traumatic stress disorder, anxiety, and depression, and that ecological cognitive SC was positively associated with mental well-being. Individual structural SC (in the form of community networks) may be psychologically protective. However, most of the evidence was cross-sectional, limiting conclusions about causal relationships. More clarity and consistency is needed in the conceptualization and measurement of SC in order to inform post-crisis mental health interventions. (Disaster Med Public Health Preparedness. 2018;12:791-802).


[Setting-up a system of health statistics collection in a rural environment in the Ivory Coast].
In order to improve the sanitary data collection system from the rural Health Centers, Ivory-Coast has modified it in acting upon the three stages of collection. At the level of rural Health Centers, it has been created, from observations and data collected in a sample of 5 centers, a new classification of diseases including 128 items allowing all male and female nurses to classify 94% of the patients examined. At intermediary level, their monthly reports are collected and checked by the chief Medical Practitioner of the Rural Health Sector, who is responsible for all medicine not pertaining to hospital centers. At central level, computerised data treatment and exploitation make possible national data spreading and back-up during the third month after the writing of their report by the nurse.


A new low cost wide-field illumination method for photooxidation of intracellular fluorescent markers.
Analyzing cell morphology is crucial in the fields of cell biology and neuroscience. One of the main methods for evaluating cell morphology is by using intracellular fluorescent markers, including various commercially available dyes and genetically encoded fluorescent proteins. These markers can be used as free radical sources in photooxidation reactions, which in the presence of diaminobenzidine (DAB) forms an opaque and electron-dense precipitate that remains localized within the cellular and organelle membranes. This method confers many methodological advantages for the investigator, including absence of photo-bleaching, high visual contrast and the possibility of correlating optical imaging with electron microscopy. However, current photooxidation techniques require the continuous use of fluorescent or confocal microscopes, which wastes valuable mercury lamp lifetime and limits the conversion process to a few cells at a time. We developed a low cost optical apparatus for performing photooxidation reactions and propose a new procedure that solves these methodological restrictions. Our "photooxidizer" consists of a high power light emitting diode (LED) associated with a custom aluminum and acrylic case and a microchip-controlled current source. We demonstrate the efficacy of our method by converting intracellular DiI in samples of developing rat neocortex and post-mortem human retina. DiI crystals were inserted in the tissue and allowed to diffuse for 20 days. The samples were then processed with the new photooxidation technique and analyzed under optical microscopy. The results show that our protocols can unveil the fine morphology of neurons in detail. Cellular structures such as axons, dendrites and spine-like appendages were well defined. In addition to its low cost, simplicity and reliability, our method precludes the use of microscope lamps for photooxidation and allows the processing of many labeled cells simultaneously in relatively large tissue samples with high efficacy.


Analysis of the Role and Regulatory Mechanism of hsa-miR-504 in Cervical Cancer Based on The Cancer Genome Atlas Database.
Objective: This study investigated the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer. Methods: The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes. Results: There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, p < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, p < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, p53 signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients (p < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer. Conclusion: The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and p53 signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer.


Hydrothermal synthesis and characterization of new pillared layered ethylenediphosphonates of molybdenum(VI), A2[Mo2O5(O3PCH2CH2PO3)] (A = NH4, Tl, Cs, Rb) and K(H3O)[Mo2O5(O3PCH2CH2PO3)].
New ethylenediphosphonates of molybdenum, A[Mo2O5(O3PCH2CH2PO3)] (A = NH4 (1), Tl (2), Cs (3), Rb (4)), and K(H3O)[Mo2O5(O3PCH2CH2PO3)] (5), have been synthesized by a hydrothermal method and structurally characterized by X-ray diffraction, spectroscopic, and thermal studies. These compounds consist of pillared anionic layers [Mo2O5(O3PCH2CH2PO3)]2-, with A+, K+, and H3O+ ions in the interlayer region as well as in the cavities within the anionic layers. Single-crystal X-ray structures of compounds 1 and 5 have been determined. They crystallize in the orthorhombic space group Cmca with Z = 8 and have the following unit cell parameters. For 1, a = 25.60(1), b = 10.016(4), and c = 9.635(3) angstroms and for 5, a = 25.63(1), b = 10.007(2), and c = 9.512(1) angstroms.


Oligomerization aiming at phosphonate analogues of oligoadenylates.
This work deals with isopolar, phosphonate-based nucleotide analogues containing a bridging P-C bond instead of the ester P-O linkage. Specifically, starting from activated derivatives 1, 2, and 3, a simple process for preparation of mixtures of short oligomers and their analyses were elaborated.


Diabetic glomerulosclerosis without concurrent diabetes mellitus.
In four adults with idiopathic nephrotic syndrome and azotemia, percutaneous renal biopsy showed diabetic glomerulosclerosis, yet none had oral glucose tolerance tests diagnostic of diabetes mellitus or funduscopic evidence of diabetic retinopathy. Possible concomitant glomerular disease that may have produced proteinuria was excluded. Well documented cases of diabetic glomerulosclerosis without concurrent glucose intolerance are uncommon, and almost 30% of such patients have a past history of diabetes. Despite the absence of overt diabetes at onset of diabetic glomerulosclerosis, these patients warrant careful monitoring of plasma glucose levels and strict control of systemic hypertension.


[Analysis on the Shanghan new theory phenomenon in the Republic of China].
During the Republic of China, influenced by the introduction of western medicine and the special social, cultural and political background, research on Shanghanlun has presented different features from those before. This phenomenon was called 'Shanghan new theory phenomenon' for this kind of theory tried to expound Shanghanlun from the view point of western medicine or ancient formula school in Japan. Shanghan new theory phenomenon had the following characteristics: the academic viewpoint of this new theory and the edition of Shanghanlun were both influenced by the ancient formula school of Japan; emphasis was put on empirical study. With academic concern, doctors in the Republic of China put forward new theories regarding what are the six meridians, etiological theory, mechanism of herbal medicine for infection, mechanism of TCM formula and comparison between TCM and western medicine. As for its historical role, the new theory school was the main force in TCM academic development and played a role in the debate about whether TCM was scientific and whether it should be abolished. It was also valuable in the combination of TCM and western medicine and diversification of researches on Shanghanlun.


Assessing patient outcomes and cost-effectiveness of nurse-led follow-up for women with breast cancer - have relevant and sensitive evaluation measures been used?
To explore how interventions using nurse-led follow-up in breast cancer care have been evaluated with a focus on patient outcomes and cost-effectiveness. As part of the advancement of breast care, nurse-led follow-up is increasingly used as an alternative to routine hospital follow-up in outpatient clinics. There is evidence suggesting that patients appear to be satisfied with the nurse-led follow-up, but there is a lack of evidence of whether this perception equates to patients' satisfaction with the model of physician-led follow-up. Systematic review. Three databases were searched, and 29 RCT were initially screened. Finally, 13 articles were critically appraised. Searches included articles between 2005-2013. The quality of appraisal assessment was inspired by the GRADE system. The results show that there are many different instruments used when evaluating nurse-led follow-up, which makes it difficult to compare the studies. Several of the studies used QoL as an outcome measure; this is a broad concept that includes several aspects ranging from social role and psychosocial issues to symptoms and therefore difficult to use as an outcome measure. Only two of the studies made any cost-effective analyses, and the results are hard to interpret. Nurse-led follow-up can potentially result in better continuity of care and the availability of more time to provide psychosocial support and address patients' information needs. However, more well-conducted research is needed before equivalence to physician-led follow-up can be assessed in terms of survival, recurrence, patient well-being and cost-effectiveness. Results from well-conducted evaluation studies of nurse-led services based on theory are needed so that relevant interventions can be implemented in clinical practice. There is a need to in future studies include cost-effectiveness analyses to compare nurse-led services with other types of follow-up.


Outbreak of clinical listeriosis in sheep: evaluation from possible contamination routes from feed to raw produce and humans.
We report the results of clinical and microbiological investigations on Listeria monocytogenes infections in a flock of 55 sheep and describe the implications for the safety of the raw milk and raw-milk cheeses produced in the on-farm dairy. The outbreak was caused by feeding grass silage, which was contaminated with 5 log10 CFU L. monocytogenes/g. Clinically, although having been fed from the same batch of silage, abortive (nine ewes), encephalitic (one ewe) and septicaemic (four ewes) forms of listeriosis were observed during the outbreak phase. As the starting point of feeding the contaminated silage was known we could calculate an incubation period of 18+/-2 and 26 days for the abortive and the encephalitic form of listeriosis, respectively. Pathologically, the septicaemic cases suffered from Listeria accumulation at comparable numbers in visceral organs but not in the brain. Only a single ewe developed central nervous symptoms and a rhomb-encephalitis was immunohistologically confirmed. In this case the infection proceeded from the nasal mucosa into the brain, with no infections of the liver, spleen and other visceral organs. Sampling of the cheese production chain, the farm environment and the persons living at the farm revealed the exposure of a farm-worker to an isolate genetically indistinguishable from the outbreak clone, obviously through the consumption of faecally contaminated bovine raw milk. The cheese under processing was free of Listeria because, as a result of intensive consultations, the farmer ensured a proper acidification of the cheese. The epidemiological findings suggest that food safety matters should be assessed in any case where infection of food-producing animals with potential human pathogens is observed.


Development of a surrogate angiogenic potency assay for clinical-grade stem cell production.
Clinical results from acute myocardial infarction (AMI) patients treated with MultiStem®, a large-scale expanded adherent multipotent progenitor cell population (MAPC), have demonstrated a strong safety and benefit profile for these cells. The mechanism of benefit with MAPC treatment is a result, in part, of its ability to induce neovascularization through trophic support. Production of clinical-grade stem cell products requires the development of lot-release criteria based on potency assays that directly reflect the fundamental mechanistic pathway underlying the therapeutic response to verify manufacturing process consistency and product potency. Using an in vitro endothelial tube formation assay, a potency assay has been developed that reflects MAPC pro-angiogenic activity. Serum-free conditioned media collected from MAPC culture induced endothelial tube formation. A proteomic survey of angiogenic factors produced by the cells in vitro revealed candidate factors linked to angiogenic potency. Three cytokines, chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF), were required for this angiogenic activity. Depletion of any of these factors from the media prevented tube formation, while adding back increasing amounts of these cytokines into the depleted serum-free conditioned media established the lower limits of each of the cytokines required to induce angiogenesis. A necessary threshold of angiogenic factor expression was established using an in vitro angiogenesis assay. By correlating the levels of the cytokines required to induce tube formation in vitro with levels of the factors found in the spent media from manufacturing production runs, detection of these factors was identified as a surrogate potency assay with defined pass/fail criteria.


The neural mechanism of biomechanical constraints in the hand laterality judgment task: A near-infrared spectroscopy study.
The mental rotation (MR) task is defined as a discrimination task between mirror-reversed images involving discrepancy in angular orientation. Various studies have shown that the MR task likely causes mental imagery, that is, visual and/or motor imagery, depending on stimulus types. When figures of rotated hands are presented to be identified as a left or right hand, reaction times (RTs) usually show an effect of biomechanical constraints (BC): a hand in a position difficult to reach with a real movement results in longer RTs. The BC effect as a marker of motor imagery has been investigated by brain function measures (fMRI, PET, EEG and MEG) as well as by RTs. Unlike other neuroimaging techniques, NIRS (near-infrared spectroscopy) imposes few physical constraints on participants and is relatively unaffected by motion artifact, which permits serial assessments of tasks in relaxed and natural environment. Focusing on these advantages, a NIRS study on motor imagery in HLJ was carried out in which we measured the brain activation during the HLJ task and a single character judgment task. In the HLJ task, both the RTs and the activity of the left superior parietal lobe (SPL) showed an interaction between Hand (left, right) and Orientation (135°, 225°) i.e., the BC effect, but not in the character judgment task. More specifically, in the analysis of BC-related activity of SPL, although the Hand×Orientation interaction was significant, the left SPL for the left hand significantly increased from 135° to 225°, but the reversed increase (from 225° to 135°) was not found for the right hand. These results suggest that left SPL is involved in the BC effect and NIRS differentiates left hand awkwardness of right-hander in the HLJ task.


The Clue.
As I stood outside of Carlos's room, I felt caught on the horns of a dilemma. It seemed impossible to truly "be there" for Carlos without sacrificing my other intern duties. This tension pervaded much of my residency training, as I often found myself spending more time completing chart notes, answering pages, and giving sign out than I did at the bedside with my patients. I knew I had a duty to "do my job"-I could not let my team down. But what about my duty to Carlos, a duty to act on my intuition and try to "get to the bottom" of his illness, if that was even possible? And what about my thirteen other patients? Wasn't I was their doctor as well? I have spent countless hours studying the ethical frameworks for medical rationing. And yet no framework could have told me how to weigh my intuition in that crucial moment of decision-making, or when it was okay to leave a few notes unfinished in order to have the time to talk with Carlos. Suddenly, I knew what I had to do.


The first permanent molar: spontaneous eruption after a five-year failure.
It is rare for a first permanent molar (FPM) to temporarily exhibit clinical features of failure of eruption, followed by regeneration of full eruptive capacity 5 years later. Indeterminate failure of eruption (IFE) is a diagnosis of exclusion where the distinction between primary failure of eruption (PFE) and mechanical failure of eruption (MFE) is unclear, including patients too young to specify. An 11-year-old girl attended the orthodontic clinic at Mid Yorkshire Hospitals NHS Trust regarding an unerupted lower right FPM. Her medical and dental trauma history was unremarkable. She presented with a Class II division 2 malocclusion in the mixed dentition, with all other FPMs fully erupted. This report documents that an unerupted FPM in an 11-year-old patient may still have the eruptive potential to become functional within the dentition. The period spent monitoring the FPM's outcome prior to surgical intervention has avoided an operation under general anaesthetic and potentially unnecessary orthodontic treatment, as the tooth subsequently erupted without treatment.


Monthly-Term Associations Between Air Pollutants and Respiratory Morbidity in South Brazil 2013-2016: A Multi-City, Time-Series Analysis.
Most air pollution research conducted in Brazil has focused on assessing the daily-term effects of pollutants, but little is known about the health effects of air pollutants at an intermediate time term. The objective of this study was to determine the monthly-term association between air pollution and respiratory morbidity in five cities in South Brazil. An ecological time-series study was performed using the municipality as the unit of observation in five cities in South Brazil (Gravataí, Triunfo, Esteio, Canoas, and Charqueadas) between 2013 and 2016. Data for hospital admissions was obtained from the records of the Hospital Information Service. Air pollution data, including PM10, SO2, CO, NO2, and O3 (µg/m3) were obtained from the environmental government agency in Rio Grande do Sul State. Panel multivariable Poisson regression models were adjusted for monthly counts of respiratory hospitalizations. An increase of 10 μg/m3 in the monthly average concentration of PM10 was associated with an increase of respiratory hospitalizations in all age groups, with the maximum effect on the population aged between 16 and 59 years (IRR: Incidence rate ratio 2.04 (95% CI: Confidence interval = 1.97-2.12)). For NO2 and SO2, stronger intermediate-term effects were found in children aged between 6 and 15 years, while for O3 higher effects were found in children under 1 year. This is the first multi-city study conducted in South Brazil to account for intermediate-term effects of air pollutants on respiratory health.


Otolith patterns of rockfishes from the northeastern Pacific.
Sagitta otolith shape was analysed in twenty sympatric rockfishes off the southern California coast (Northeastern Pacific). The variation in shape was quantified using canonical variate analysis based on fifth wavelet function decomposition of otolith contour. We selected wavelets because this representation allow the identifications of zones or single morphological points along the contour. The entire otoliths along with four subsections (anterior, ventral, posterodorsal, and anterodorsal) with morphological meaning were examined. Multivariate analyses (MANOVA) showed significant differences in the contours of whole otolith morphology and corresponding subsection among rockfishes. Four patterns were found: fusiform, oblong, and two types of elliptic. A redundancy analysis indicated that anterior and anterodorsal subsections contribute most to define the entire otolith shape. Complementarily, the eco-morphological study indicated that the depth distribution and strategies for capture prey were correlated to otolith shape, especially with the anterodorsal zone.


Measurement of renal function in pre-ESRD patients.
The measurement of renal function in pre-dialysis patients is important in order to determine the appropriate time to begin renal replacement therapy, to forecast the start, and to compare, in groups of patients, the efficiency of different treatments that limit renal disease progression. The most reliable methods, such as inulin clearance or measurement by radioisotopes, are too awkward for the usual clinical follow-up of patients. Although much simpler and almost as reliable, the use of iohexol radiologic contrast does not allow the frequent monitoring of the patient either. The determinations of the plasmatic creatinine and its clearance or the estimate of the glomerular filtration rate by means of equations derived from the creatinine are the methods most often used in order to measure renal function, although not without problems in pre-dialysis. In order to try to overcome such problems, more precise equations and procedures, including the measurement of averaged urea-creatinine clearance or creatinine clearance with cimetidine, have been designed that better estimate the glomerular filtration rate. However, none of these methods is totally reliable in pre-dialysis. A new endogen marker, cystatin C, has advantages over creatinine, though more studies are needed in pre-dialysis in order to ascertain its use. The initial proposal of the National Kidney Foundation's Kidney Disease Outcome Quality Initiative (DOQI) guidelines to use weekly Kt/V and nutritional parameters to determine the time for starting renal replacement therapy has widened the prospects of the debate on the measurement of renal function in pre-dialysis, but further work is required to define their role in pre-dialysis patients' follow-up.


Clinical significance of RET mutation screening in a pedigree of multiple endocrine neoplasia type 2A.
The clinical characteristics and RET proto-oncogene (RET‑PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease. Clinical characteristics of a single MEN2A patient were analyzed. Genomic DNA was extracted from the peripheral blood of the proband and 10 family members. The 21 exons of RET‑PO were PCR amplified and the amplified products were sequenced. Of the family members, 5 exhibited a C634Y (TGC→TAC) missense mutation in exon 11 of RET‑PO, among which 2 family members were screened as mutation carriers, while the others did not exhibit clinical symptoms of the mutation. The screening and analysis of RET‑PO mutations for the MEN2A proband and the family members suggests potential clinical phenotypes and enables assessment of the risk of disease development, thus providing useful information for determining the surgical timing of preventive thyroid gland removal.


[A monoclonal antibody against peripheral human blood monocytes (RoMo-1)].
The monoclonal IgG2a-antibody RoMo-1 binds to peripheral human blood monocytes but does not react with other blood cells, tissue macrophages, HL-60, K 562 or U 937. It seems possible, that the antibody defines an antigen expressed on the premonocytic and monocyte stages of cells from the mononuclear phagocytic system only. The antibody is cytotoxic.


Hepatoprotective Effect of Cissus quadrangularis Stem Extract Against Rifampicin-induced Hepatotoxicity in Rats.
The study was designed to investigate the hepatoprotective activity of methanol extract of Cissus quadrangularis against rifampicin-induced hepatotoxicity in rats.The coarse powder of the shade dried stem of Cissus quadrangularis was subjected to successive extraction in a Soxhlet apparatus using solvents petroleum ether (60-80°) and methanol. Liver damage was induced in Wistar rats by administering rifampicin (54 mg/kg, p.o.) once daily for 30 days. Methanol extract of Cissus quadrangularis (500 mg/kg, p.o) was administered 1 h prior to the administration of rifampicin (54 mg/kg, p.o.) once daily for 30 days. Silymarin (50 mg/kg p.o) used as reference drug. Elevated levels of aspartate transaminase, alanine transaminase, alkaline posphatase and bilirubin following rifampicin induction were significantly lowered due to pretreatment with methanol extract of Cissus quadrangularis. Rifampicin administration significantly increased lipid peroxidation and decreased antioxidant activities like reduced glutathione, superoxide dismutas and catalase. Pretreatment of rats with methanol extract of Cissus quadrangularis significantly decreased lipid peroxidation and increased the antioxidant activities. Histology of the liver section of the animals treated with the methanol extract of Cissus quadrangularis further confirms the hepatoprotective activity. The results of the present study indicated the hepatoprotective effect of methanol extract of Cissus quadrangularis which might be ascribable to its antioxidant property due to the presence of β-carotene.


Arachidicoccus rhizosphaerae gen. nov., sp. nov., a plant-growth-promoting bacterium in the family Chitinophagaceae isolated from rhizosphere soil.
Three novel bacterial strains, designated Vu-144(T), Vu-7 and Vu-35, were isolated on minimal medium from rhizosphere soil of field-grown cowpea and subjected to a taxonomic study using a polyphasic approach. Cells of the strains were Gram-stain-negative, non-motile, non-spore-forming, coccoid rods, and formed non-pigmented colonies. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Vu-144(T) was affiliated with an uncultivated lineage of the phylum Bacteroidetes. Its closest phylogenetic neighbour was the recently described species Niastella populi, a member of the family Chitinophagaceae, with just 90.7 % sequence similarity to the type strain. The only isoprenoid quinone detected was menaquinone 7 (MK-7). The fatty acid profiles showed large amounts of iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G and minor amounts of summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), C16 : 0 and other fatty acids, allowing the differentiation of the strains from other genera. The G+C content of the genomic DNA of the three strains ranged from 43.1 to 44.3 mol%. In addition to phosphatidylethanolamine, the major polar lipids were three unidentified aminophospholipids (APL1-APL3), two unidentified phospholipids (PL1, PL2) and three unidentified lipids (UL1-UL3). Biochemical test patterns also differed from those of Niastella populi and members of other genera. All three isolates showed plant-growth-promoting properties, e.g. the ability to produce indole-3-acetic acid and NH3 and to solubilize phosphate, utilized 1-aminocyclopropane 1-carboxylate (ACC) as a sole source of nitrogen and possessed the ACC deaminase enzyme. The novel isolates readily colonized roots and stimulated growth of tomato and cowpea under glasshouse conditions. Inoculated plants showed a 45-60 % increase in dry matter weight with respect to uninoculated controls. On the basis of the evidence from our polyphasic study, isolate Vu-144(T) represents a novel genus and species in the family Chitinophagaceae, for which the name Arachidicoccus rhizosphaerae gen. nov., sp. nov. is proposed. The type strain of Arachidicoccus rhizosphaerae is Vu-144(T) ( = KCTC 22378(T) = NCIMB 14473(T)).


Anomalous origin of left coronary artery with aortopulmonary window - a case report with surgical correction and delayed control.
A 9-month-old male baby was investigated for a massive left-to-right shunt at the arterial level. On right heart catheterization a patent ductus could not be demonstrated but retrograde arterial angiography showed an aorto-pulmonary window. During corrective surgery on cardiac bypass, the left coronary artery was found to arise from the aorto-pulmonary window, this was corrected by dividing the communication distal to the origin of the left coronary artery. On follow-up investigation 6 months after operation the baby was without symptoms and showed a fully functional left coronary artery. To our knowledge this is the first case of such a congenital anomaly to be described.


Revisiting the Tropospheric OH-Initiated Unimolecular Decomposition of Chlorpyrifos and Chlorpyrifos-Methyl: A Theoretical Perspective.
Based on density functional theory (DFT) electronic structure calculations with dispersion correction, we propose new reaction pathways in which no extra reaction step is necessary to account for the formation of 3,5,6-trichloro-2-pyridynol (TCP) within the process of tropospheric OH-initiated unimolecular decomposition of chlorpyrifos (CLP) and chlorpyrifos-methyl (CLPM). Chlorpyrifos and its analogous compound are among the most used organophosphorus pesticides worldwide, and their unimolecular decomposition in the troposphere is a dominant process of removal in the gas phase. The reaction pathways that we put forward have turned out to be the most exergonic ones among the three possible routes for the attack of the hydroxyl radical to the thiophosphoryl (P═S) bond of both CLP and CLPM. The results showed that the reaction is thermodynamically controlled with the formation of P-bonded adducts via a six-membered ring. The unimolecular decomposition of such reactive intermediates takes place with small energy barriers (less than 3 kcal mol-1) and is distinguished by hydrogen transfer to the nitrogen atom of the aromatic ring, resulting in the formation of 3,5,6-trichloro-2-pyridinol (TCP) and dialkyl phosphate radical (DAP·) product complexes in a single step.