Does type of funding affect reporting in network meta-analysis? A scoping review of network meta-analyses.
Evidence has shown that private industry-sponsored randomized controlled trials (RCTs) and meta-analyses are more likely to report intervention-favourable results compared with other sources of funding. However, this has not been assessed in network meta-analyses (NMAs). To (a) explore the recommendation rate of industry-sponsored NMAs on their company's intervention, and (b) assess reporting in NMAs of pharmacologic interventions according to their funding type. Design: Scoping review of published NMAs with RCTs. We used a pre-existing NMA database including 1,144 articles from MEDLINE, EMBASE and Cochrane Database of Systematic Reviews, published between January 2013 and July 2018. NMAs with transparent funding information and comparing pharmacologic interventions with/without placebo. We captured whether NMAs recommended their own or another company's intervention, classified NMAs according to their primary outcome findings (i.e., statistical significance and direction of effect), and according to the overall reported conclusion. We assessed reporting using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension to NMA (PRISMA-NMA) 32-item checklist. We matched and compared industry with non-industry NMAs having the same research question, disease, primary outcome, and pharmacologic intervention against placebo/control. We retrieved 658 NMAs, which reported a median of 23 items in the PRISMA-NMA checklist (interquartile range [IQR]: 21-26). NMAs were categorized as 314 publicly-sponsored (PRISMA-NMA median 24.5, IQR 22-27), 208 non-sponsored (PRISMA-NMA median 23, IQR 20-25), and 136 industry/mixed-sponsored NMAs (PRISMA-NMA median 21, IQR 19-24). Most industry-sponsored NMAs recommended their own manufactured drug (92%), suggested a statistically significant positive treatment-effect for their drug (82%), and reported an overall positive conclusion (92%). Our matched NMAs (25 industry vs 25 non-industry) indicated that industry-sponsored NMAs had favourable conclusions more often (100% vs 80%) and were associated with larger (but not statistically significantly different) efficacy effect sizes (in 61% of NMAs) compared with non-industry-sponsored NMAs. Differences in completeness of reporting and author characteristics were apparent among NMAs with different types of funding. Publicly-sponsored NMAs had the best reporting and published their findings in higher impact-factor journals. Knowledge users should be mindful of this potential funding bias in NMAs.


Carboxylated multiwalled carbon nanotubes/polydimethylsiloxane, a new coating for 96-blade solid-phase microextraction for determination of phenolic compounds in water.
A new thin-film, carboxylated multiwalled carbon nanotubes/polydimethylsiloxane (MWCNTs-COOH/PDMS) coating was developed for 96-blade solid-phase microextraction (SPME) system followed by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The method provided good extraction efficiency (64-90%) for three spiked levels, with relative standard deviations (RSD)≤6%, and detection limits between 1 and 2 μg/L for three phenolic compounds. The MWCNTs-COOH/PDMS 96-blade SPME system presents advantages over traditional methods due to its simplicity of use, easy coating preparation, low cost and high sample throughput (2.1 min per sample). The developed coating is reusable for a minimum of 110 extractions with good extraction efficiency. The coating provided higher extraction efficiency (3-8 times greater) than pure PDMS coatings.


A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia.
Non-alcoholic fatty liver disease (NAFLD) is a major complication linked with the metabolic syndrome associated with dyslipidemia, inflammation, and oxidative stress. Impact of type 2 diabetes with hyperlipidemia in NAFLD has to be established, as well as the utility of commonly prescribed anti-diabetic and lipid-lowering agents in improving liver injury markers. Genetic type 2 diabetic Goto-Kakizaki rats were fed with a high-fat diet to test hepatic effects of type 2 diabetes with hyperlipidemia and the effect of atorvastatin and insulin, individually and in combination, in systemic and hepatic inflammatory and oxidative stress markers. High-fat diet aggravated fasting glycemia, systemic and liver lipids, and inflammatory and oxidative stress markers. Individual treatments improved glycemic and lipid profiles, but failed to improve inflammatory markers, whereas insulin was able to reduce liver oxidative stress parameters. Combination of insulin and atorvastatin further improved glycemic and lipid profiles and decreased circulating C-reactive protein levels and liver inflammatory and oxidative stress markers. Insulin and atorvastatin combination leads to better glycaemic and lipid profiles and to better protection against liver inflammation and oxidative stress, giving a superior level of liver protection in type 2 diabetic with hyperlipidemia.


The organization of adherens junctions in mouse osteoblast-like cells (MC3T3-E1) and their modulation by triiodothyronine and 1,25-dihydroxyvitamin D3.
Cadherin-mediated cell-cell adhesion is essential for the development and survival of multicellular tissues. Thus it is hypothesized that these molecules also play a fundamental role for the development and maintenance of bone by mediating cellular crosstalk between osteogenic cells and by providing targets for the sorting and migration of osteogenic precursors toward the bone surface. We describe the localization of cadherin-11 and N-cadherin along the cell margins of mouse osteoblast-like cells, the colocalization of "pancadherin" with alpha-catenin, beta-catenin, p120, and vinculin, and the association of these complexes with the actin microfilaments. Furthermore, we measured the influence of cell confluency and the effects of the osteogenic hormones triiodothyronine (T3) and 1,25-dihydroxyvitamin D3 (D3) on these parameters. By mRNA studies we found the abundantly expressed cadherin-11 being unaffected during T3- and D3-induced osteoblastic differentiation. However, protein levels of N-cadherin and "pancadherin" were strongly suppressed by D3. We also observed a clear distinction in cadherin immunolocalization when comparing confluent control and confluent hormone-treated cultures. Immunoprecipitation experiments indicated that vinculin is part of the junctional complex, and that the association of "pancadherin"/beta-catenin is strongly increased after treatment with T3 which might influence the functional competence of cell-cell contacts. Thus, this study demonstrates the molecular organization of adherens junctions in mouse osteoblastic MC3T3-E1 cells and their sensitivity to the osteogenic factors T3 and D3 in confluent cultures.


Synthetic β-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD.
Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a β hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-β plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC50 value of 67 μg/ml against AChE and 96 μg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC50 value observed as 171 μg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.


Governing taste: data, temporality and everyday kiwifruit dry matter performances.
Data is essential to governing those emerging matters of concern that confront the agrifood every day. But data is no neutral intermediary. It disrupts, exposes, and creates new social, economic, political, and environmental possibilities, whilst simultaneously hiding, excluding, and foreclosing others. Scholars have become attuned to both the constitutive role of data in creating everyday worlds, and the need to develop critical accounts of the materialities, spatialities and multiplicities of data relationships. Whereas this emerging work develops insight to the capacity for data topologies to reterritorialise the spatial performances of everyday life, it has largely reduced the associated temporal dimensions to matters of fact. The effect of these performances has been to naturalize the temporal quality of speed and elide the multiple temporalities required to enact contemporary data worlds. Applying the lenses of infrastructuring, performativity and ferality, this paper explores temporality and data in the everyday worlds produced through the New Zealand kiwifruit industry's focus on dry matter. The paper argues that temporalities are deeply embedded in the kiwifruit industry's data relations. We show that while temporal data relations are critical to the industry, we also highlight ways in which those relations introduce new, potentially destabilizing performances into kiwifruit relations.


The use of the harmonic scalpel vs conventional knot tying for vessel ligation in thyroid surgery.
The technique of thyroidectomy has undergone little change in several decades. The harmonic scalpel, using ultrasonic frictional heating to ligate vessels, is widely used in laparoscopic surgery, but there is little experience in open thyroidectomy. We hypothesized that the use of the harmonic scalpel could lead to a significant reduction in operative time as compared with knot tying in thyroid surgery. Retrospective case-controlled study. Teaching institution. One hundred seventy-one consecutive patients undergoing lobectomy or total thyroidectomy by one surgeon (A.E.S.). Eighty-six patients underwent thyroid surgery with the conventional clamp-and-tie technique (lobectomy, n = 49; total thyroidectomy, n = 36) and 85 with the harmonic scalpel (lobectomy, n = 38; total thyroidectomy, n = 47). Demographics, pathological characteristics, thyroid size, operative time, blood loss, and complications using a 2-tailed t test, chi(2)test, and Wilcoxon rank sum test. The 2 groups were similar regarding age and sex. There were no intraoperative complications. Mean +/- SD thyroid size tended to be larger in the harmonic scalpel group for both lobectomy (5.1 +/- 2.6 cm vs 4.2 +/- 2.2 cm; P =.06) and total thyroidectomy specimens (6.3 +/- 3.8 cm vs 4.8 +/- 2.9 cm; P =.08) compared with the conventional technique. Mean +/- SD operative time was shorter in the harmonic scalpel group compared with the conventional technique group for both lobectomy (89 +/- 20 minutes vs 115 +/- 25 minutes; P<.01) and total thyroidectomy (132 +/- 39 minutes vs 161 +/- 42 minutes; P<.01) procedures. There was no difference between the 2 techniques regarding the amount of blood loss for different procedures. There was no effect of tumor size on operative time (Pearson correlation factors: 0.14 for total, 0.21 for unilateral thyroidectomy). The use of the harmonic scalpel for the control of thyroid vessels during thyroid surgery is safe, and it shortens the operative time by almost 30 minutes compared with the conventional technique for both unilateral lobectomy or total thyroidectomy procedures.


Changes in nerve cells of the nucleus basalis of Meynert in Alzheimer's disease and their relationship to ageing and to the accumulation of lipofuscin pigment.
The number of nerve cells in the nucleus basalis of Meynert in normally aged persons is reduced by 30% by 90 years of age and cytoplasmic RNA content and nucleolar volume by about 20%. In Alzheimer's disease the changes are greatly exacerbated, with the cell number being depleted by a further 60% and cytoplasmic RNA content and nucleolar volume by an extra 35%. Moreover, younger patients with Alzheimer's disease show a much greater difference from controls of the same age than do older patients; indeed, by 90 years of age the levels of these changes are similar in Alzheimer's disease and in old age alone. Lipofuscin content is increased to a similar extent with age in both Alzheimer's disease and control patients and was associated with loss of cytoplasmic RNA content and nucleolar volume in both groups. It is suggested that mechanisms which result in the accumulation of this pigment during life also lower the capability of cells of the nucleus basalis of Meynert to withstand disease pathogens, leading to a certain degree of change in old age alone and one which in other persons may be compounded by secondary factors giving the extreme degeneration of Alzheimer's disease.


Non-muscle invasive transitional cell carcinoma of the distal ureter and bladder with lung metastasis: A case report and literature review.
Non-muscle invasive transtitional cell carcinoma (TCC) with metastases is exceedingly rare. We report the case of a 78-year old man with an incidental finding of a non-muscle invasive TCC of the left distal ureter during treatment for Duke's B Colon cancer. Following laparoscopic nephro-ureterectomy (LNU) he had two further superficial recurrences in the bladder over a 14-month period which underwent transurethral resection (TUR). On surveillance imaging for his colorectal cancer follow-up a lung nodule was detected and video-assisted thoracic surgical (VATS) resection of the lesion showed it to be TCC in origin. He was referred to oncology for chemotherapy and remains clinically well. A Literature search found only three other such cases and the ureteric TCC is the most likely source of the metastasis. This occurrence is exceedingly rare.


[Factors causing short-term periodic changes in the numbers of bacteria in the superficial layer of sludge and in the water near the bottom].
Rhythmical temporal changes in the number of bacterial populations inhabiting the surface ooze layer and the water layer above it have been found to depend on two processes: (1) the ability of bacteria for periodic intensive growth followed by death of the cells and (2) the participation of zooplankton in consuming the bacterial cells for nourishment. The total bacterial number in samples depends on which of the two processes prevails.


Granular computing in mosaicing of images from capsule endoscopy.
This article introduces methods for modeling compound granules used in algorithms which could successfully construct a mosaic from the images coming from an endoscope capsule. In order to apply the algorithm, combined images must have a common area where the correspondence of points is determined. That allows to determine the transformation parameters to compensate movement of the capsule that occurs between moments when the mosaic images were acquired. The developed algorithm for images from the capsule endoscopy has proved to be faster and comparably accurate as commercial GDB-ICP algorithm.


Comparing belief in short-term versus long-term consequences of smoking and vaping as predictors of non-use in a 3-year nationally representative survey study of US youth.
Efforts to prevent youth tobacco use are critical to reducing smoking-related deaths in the USA. Anti-tobacco messaging often focuses on the severe long-term consequences of smoking (eg, fatal lung disease, cancer). It is unclear whether these long-term consequences are more likely to deter youth use than shorter term consequences (eg, headaches, friend disapproval). A nationally representative 3-year rolling survey of adolescents and young adults (ages 13-26 years) measured belief in potential consequences of two types of tobacco products: combustible cigarettes (n=11 847) and electronic cigarettes (n=4470) as well as intentions and current use. Independent coders classified 23 consequences as either short or long term. Logistic regression tested the associations between short-term (vs long-term) beliefs and current intentions, as well as non-smoking behaviour at 6-month follow-up. Believing in both short-term and long-term consequences was associated with outcomes, but short-term beliefs were more highly associated with anti-smoking (OR=1.40, 95% CI (1.30 to 1.51)) and anti-vaping (OR=2.10, 95% CI (1.75 to 2.52)) intentions and better predicted non-smoking behaviour at follow-up, controlling for prior use (OR=1.75, 95% CI (1.33 to 2.31)). These results support temporal discounting by adolescents and young adults and suggest health communication efforts aiming to reduce youth tobacco use should emphasise shorter term consequences.


NeuMa - the absolute Neuromarketing dataset en route to an holistic understanding of consumer behaviour.
Neuromarketing is a continuously evolving field that utilises neuroimaging technologies to explore consumers' behavioural responses to specific marketing-related stimulation, and furthermore introduces novel marketing tools that could complement the traditional ones like questionnaires. In this context, the present paper introduces a multimodal Neuromarketing dataset that encompasses the data from 42 individuals who participated in an advertising brochure-browsing scenario. In more detail, participants were exposed to a series of supermarket brochures (containing various products) and instructed to select the products they intended to buy. The data collected for each individual executing this protocol included: (i) encephalographic (EEG) recordings, (ii) eye tracking (ET) recordings, (iii) questionnaire responses (demographic, profiling and product related questions), and (iv) computer mouse data. NeuMa dataset has both dynamic and multimodal nature and, due to the narrow availability of open relevant datasets, provides new and unique opportunities for researchers in the field to attempt a more holistic approach to neuromarketing.


Implementation and development of federally-funded systems of care over time.
This study describes development in federally funded systems of care. Data for this study were collected using the System of Care Assessment that rated grantees' enactment of system of care principles in the infrastructure and service delivery domains. Data were collected by trained raters who conducted several site visits over the funding period. This study described system development over time across 61 sites and tested whether gains were statistically significant. Latent profile analysis was used to explore whether sites could be meaningfully grouped based on their baseline service delivery domain scores. Differences across groups were tested in terms of community, system, and client characteristics. Differential growth across groups was also examined. Overall, systems of care developed over time in both the infrastructure and service delivery domains. Although infrastructure scores were generally lower than service delivery scores, greater gains were seen for the infrastructure domain. Three groups of sites were identified that could be distinguished in terms of degree of development overall, and for specific system of care principles. The groups of sites differed in terms of community factors, system features, and client characteristics. In addition, repeated measures analyses found differential growth in system development over time across groups.


Cytokines and adherence molecules involved in spontaneous dendritic cell-lymphocyte clustering in skin afferent lymph.
The skin afferent lymph dendritic cell (DC) spontaneously forms clusters with autologous T cells. The role of adhesion molecules and cytokines in this process was investigated. Analysis of the expression of adhesion receptors on the canine peripheral lymph DC revealed the presence of CD54, CD58, CD18 as well as CD49d and CD49e molecules and cell surface fibronectin. The CD54 and CD58 molecules were found to play a key role in the 'spontaneous' lymph cell clustering. Antibody against fibronectin, a substrate for CD49d and CD49e receptors, reduced DC-lymphocyte binding. Analysis of the effect of cytokines revealed that the pro-inflammatory IL1 beta rather than IL1 alpha, and TNF alpha may be responsible for the enhanced lymph cell in vitro clustering. The IL6 had no such augmenting effect. The enhancing effect of endogenous IL1 beta present in lymph was reduced by the IL1 beta neutralizing antibody. The effect of exogenously added IL1 beta was also limited by the IL1 receptor antagonist. The IL1Ra alone had no effect on cell binding, even when used in the high doses. Neutralizing of IL1Ra in lymph with the specific antibody brought about augmented cluster formation. The enhancing properties of TNF alpha on cell binding were reduced by the TNF alpha neutralizing antibody. The IL10 significantly limited lymph DC cluster formation with T cells. In conclusion, these data demonstrate that the present in lymph IL1 beta and TNF alpha may be responsible for the observed in vitro enhanced cluster formation of lymph DC with autologous T lymphocytes. Cell binding can be reduced by IL1Ra and by IL10. It provides insight into the potential clinical use of these inhibitors.


Hormonal secretion of cultured rat ovarian follicles isolated at various hours of proestrus.
Rat ovarian follicles were isolated at nine different times during proestrus and cultured for 3 d. During the period of cultivation, estrogen and progestagen secretion was measured. Other follicles were dissected out at the same time periods and analyzed directly for these hormones. The most intense hormone release was observed during the first 24 h in culture. The concentration of steroids secreted in vitro by follicles previously collected on the morning of proestrus was relatively low. The secreted estrogen concentration increased gradually from follicles previously isolated at later times during proestrus, with a maximum at 1800. The peak secretion of progestagens in culture was from follicles isolated at 2000. There was a marked decrease in secretion of both hormones from follicles isolated past their optimal times. The same secretion pattern of estrogens and progestagens was shown by follicles in vitro at 24 h as with similar follicles in vivo, according to their time of isolation. From these results it is evident that the normal rhythm of steroid secretion, predetermined at the time of follicle excision, was maintained during 24 h in organ culture. After a longer period in culture, the dynamics of hormone synthesis became altered, although follicles appeared morphologically normal up to 48 h.


Neurotoxic effects of the anti-varicella zoster virus agent 2'-valeryl-6-methoxypurine arabinoside in monkeys and rats dosed orally for 90 days.
The 2'-valerate ester of 6-methoxypurine arabinoside (170U88), a nucleoside analog with anti-varicella zoster virus (VZV) activity, was given to monkeys and rats. In subchronic preclinical toxicity studies, dosing was by gavage to monkeys (distilled water vehicle) and rats (0.5% methylcellulose vehicle) for 90 days. Groups of 5 male and 5 female monkeys (Macaca fascicularis) were given 170U88 at 0, 25, 50, or 100 mg/kg/day. The daily dose was given in two equal portions with 6 hr between doses. Monkeys in the high-dose group lost weight. Food consumption was decreased for mid- and high-dose monkeys and for low-dose female monkeys. Slightly decreased values for erythrocyte and leukocyte counts at the mid- and high dose were fully reversed during an 8-week recovery period. Two high-dose male monkeys and a middose female monkey developed signs of central nervous system toxicity and were necropsied before dosing was complete. These signs were first observed in the fifth week of dosing and included body tremors, incoordination, reduced activity, sleepiness, stupor, and lack of eye tracking. Axonal lesions were observed in histologic sections of sciatic nerve in monkeys at all dose levels. Neither the signs of central nervous system toxicity nor the axonal lesions reversed during the 8-week recovery period. Groups of 14 male and 14 female CD rats (Sprague-Dawley derived) were given single daily doses of 170U88 at 0, 150, 300, or 600 mg/kg. Body weights were decreased at all dose levels and food consumption was decreased for mid- and high-dose rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Get up, stand up: a randomized controlled trial to assess the effectiveness of a messenger-based intervention to reduce sedentary behavior in university students.
Sedentary behavior is a severe and independent risk factor for health. According to current research, sitting time is at a dangerously high level. Especially young adults show a high prevalence compared to others. The study aimed to assess the effectiveness of a 6-week messenger-based intervention to reduce sedentary behavior in university students. The 345 university students that enrolled were randomly assigned to the intervention group (n = 173) and control group (n = 172). Randomization and allocation to the trial group were computer assisted. The trial was conducted remotely, without any personal contact. A drop out of 276 participants led to a primary analysis of 71 (IG n = 41; CG n = 31) participants. Sedentary behavior was assessed online using the Heidelberg Questionnaire for the Assessment of Sitting Behavior, at 5 time points: baseline (T0), 2 weeks (Z1), 4 weeks (Z2) 6 weeks (end of the intervention, T1), and follow-up 4 weeks after intervention (T2). Mixed ANOVA was carried out for T0 and T1 to reveal interaction effects between time and group. Mean differences show a highly practically and statistically relevant reduction in sitting time in the intervention group of 60 min between baseline and T1. No sustained effect of the intervention could be detected by analyzing sitting times at follow-up, 4 weeks after the end of the intervention. Reduction in sedentary behavior in the intervention group after 6 weeks shows that the intervention is practically and statistically relevant. Limitations concerning the assessment method (questionnaire) as well as the sample size should be considered. The trial serves as a pilot study. However, the positive outcome of sitting time reduction paves the way for further research in this field. The online version contains supplementary material available at 10.1007/s10389-022-01747-7.


New structural classes of antimalarials.
Malaria remains a major vector borne disease claiming millions of lives worldwide due to infections caused by Plasmodium sp. Discovery and development of antimalarial drugs have previously been dominated majorly by single drug therapy. The malaria parasite has developed resistance against first line and second line antimalarial drugs used in the single drug therapy. This has drawn attention to find ways to alleviate the disease burden supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has now mandated the revision of the current antimalarial pharmacotherapy. Research efforts of the past decade led to the discovery and identification of several new structural classes of antimalarial agents with improved biological attributes over the older ones. The following is a comprehensive review, addressed to the new structural classes of heterocyclic and natural compounds that have been identified during the last decade as antimalarial agents. Some of the classes included herein contain one or more pharmacophores amalgamated into a single bioactive scaffold as antimalarial agents, which act upon the conventional and novel targets.


A large dumbbell glossopharyngeal schwannoma involving the vagus nerve: a case report and review of the literature.
Schwannoma arising from the glossopharyngeal nerve is a rare intracranial tumor. Fewer than 40 cases have been reported. Accurate pre-operative diagnosis and optimal treatment are still difficult. We present one case of schwannoma originating from the ninth cranial nerve with palsies of the trigeminal nerve, facial-acoustic nerve complex, and vagus nerve in addition to ninth nerve dysfunction. Magnetic resonance imaging showed tumors located in the cerebellopontine angle with extracranial extension via the jugular foramen, with evident enhancement on post-contrast scan. Surgical management single-staged with the help of gamma knife radiosurgery achieved total removal. Glossopharyngeal schwannoma is devoid of clinical symptoms and neurological signs. High resolution magnetic resonance imaging may play a key role as an accurate diagnostic tool. A favorable option of approach and appropriate planning of surgical strategy should be the goal of operation for this benign tumor.


Is partial colectomy the operation of choice in pediatric Clostridium difficile colitis?
This study examined the national trends in incidence and surgical management of pediatric Clostridium difficle colitis (CDC) hospitalizations. This was a cross-sectional Nationwide Inpatient Sample (NIS) analysis of pediatric CDC from 2000 to 2008. Data analysis included patient demographics, procedures, length of stay (LOS), total hospital charges (THC), and in-hospital mortality. During the 9-year study period, the total number of CDC hospitalizations per year increased almost twofold, from 2,513 in 2000 to 4,817 in 2008. The rate per 100,000 discharges followed a similar trend, increasing from 38.08 in 2000 to 72.57 in 2008. Abdominal colectomy was performed in 0.35 %, with partial colectomy performed more often than total colectomy. Mortality, mean LOS, and mean THC were not statistically different between partial versus total colectomy. Children with ulcerative colitis were more likely to undergo total colectomy, (OR 35.700, CI 11.025-115.98, P < 0.001). Infants under the age of 1 year were less likely to undergo total colectomy (OR 0.568, 0.477-0.677, P < 0.001). Pediatric hospitalizations for CDC are on the rise. Partial colectomy is performed more often than total colectomy without statistical compromise of mortality, length of stay, and total hospital charges. Further studies are needed to determine the standard surgical management of pediatric CDC.


Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice.
Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice. MPS I mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.


Determination of radiolabelled proline and hydroxyproline in collagen hydrolysates by high-performance liquid chromatography with on-line radiometric detection.
Radiolabelled proline and hydroxyproline were separated on a C8 column (10 cm X 4.6 mm I.D.) with 10.4 mM sodium dodecyl sulphate in water-n-propanol (88:12, v/v) (pH 2.6) as the mobile phase at a flow-rate of 0.6 ml/min. The retention times of hydroxyproline and proline were 5 and 8 min, respectively. On-line radiometric detection was performed either in a homogeneous mode (liquid scintillator was added to the column effluent in the ratio 3.33:1) or in a heterogeneous mode (the detection cell was packed with a solid scintillator and 0.1 M ammonia was mixed with the column effluent in the ratio 1:6 in order to prevent adsorption of amino acids on the cell packing). Detection limits were in the range 100-900 dpm for individual isotopes and detection modes and the reproducibilities were better than 10%. The application of the method to a collagen synthesis study is reported.


Laparoscopic treatment of rectovaginal fistulas. Feasibility, technical details, and functional results of a rare anorectal malformation.
Rectovaginal fistulas are a rare variety of anorectal malformations. Eight patients with this anomaly among 420 children with anorectal malformations were treated in our center. We used a laparoscopic approach in 5 of the children. The aim of this study is to define the feasibility and technical details of laparoscopy in the treatment of these patients as compared with those treated by posterior sagittal anorectoplasty (PSARP) and to evaluate the preliminary results. Three patients were treated with a PSARP starting February 2000 (group 1 [GI]). The laparoscopic approach (laparoscopic treatment [LT]) was used in the next 5 girls starting in November 2002 (group 2 [G2]). All patients were operated on by the authors. In LT cases, we used 3 ports. The rectum was dissected laparoscopically, and the fistula was transected. An assisted anorectal pull-through was then performed using a minimal perineal incision. Clinical features, age at operation, associated anomalies, ratio/sacrum (sacral ratio [SR]), distal colostogram, operative findings, complications, urinary continence, voluntary bowel movements, constipation, soiling, and requirements of bowel management program were analyzed. Patients older than 3 years and 6 months and with more than 3 months after colostomy closure were included in the analysis of functional results. The mean age at the time of operation was 21.8 months. Urogenital anomalies were seen in 6 (75%) of the 8 girls. Two patients had SRs less than 0.6. Only 3 patients in each group were considered for evaluation of functional results. Mean age was 67 months in 3 (G1) and 64 months in 3 (G2) patients. All 6 patients were continent of urine. Only 1 in G1 had an SR less than 0.6. Voluntary bowel movements were present in 1 patient in G1 and 2 in G2. One patient in G1 had severe constipation and grade 2 soiling requiring bowel management program (SR <0.6), and 1 patient in G2 had occasional soiling. Laparoscopy allowed an optimal view of the pelvis and helped to achieve a low dissection of the fistula. Although the number of patients in this study is few, functional results with LT seem to be comparable to the open PSARP approach when done by experienced pediatric surgeons. The laparoscopic approach may be considered as an option for the treatment of this rare anomaly.


Influence of pulse frequency Er:YAG laser on the tensile bond strength of a composite to dentin.
To evaluate the influence of different pulse frequencies of Er:YAG laser on the tensile bond strength of a composite to dentin. The dentin surface treatment was performed by Er:YAG laser at 1, 2, 3 and 4Hz pulse frequencies and 80 mJ, for 20 seconds, followed by etching. The control group was etched by phosphoric acid solely. The Single Bond/Z250 system was used. The specimens were subjected to tensile strength tests in a testing machine (0.5mm/minute) after water storage (37 degrees C/24 hours). The averages in MPa were: 1Hz: 13.45 (+/- 5.31); 2Hz: 9.54 (+/- 2.13); 3Hz: 7.29 (+/- 1.26); 4Hz: 7.41 (+/- 2.44) and control group: 16.95 (+/- 2.57). The Kruskal-Wallis test revealed statistically significant difference. The increased frequency of the Er:YAG laser decreased the composite bond strength.


Psychometric properties of the Brazilian Portuguese version of the Copenhagen Burnout Inventory (CBI) in healthcare professionals.
Burnout syndrome (BS) in healthcare professionals (HCP) has been a major concern, and even more so during the coronavirus disease 2019 (COVID-19) pandemic. The need for adequate tools to assess BS is urgent. The objective of this study was to validate the Brazilian Portuguese version of the Copenhagen Burnout Inventory (CBI) in HCP. The sample comprised 1,054 Brazilian HCP. Data were collected for 1 month (May-2020 to June-2020) using an online self-administered questionnaire. All three CBI dimensions demonstrated optimal reliability. All consistency measures attained values > 0.90. Split-half correlation values with Spearman-Brown reliability were higher than 0.8. The parallel analysis suggested two factors: personal burnout (PB) and work-related burnout (WB) items were associated with factor 1, and client-related burnout (CB) items were associated with factor 2. Our study corroborates the validity of the Brazilian Portuguese version of the CBI, pointing to a close relation between PB and WB in HCP. A public domain tool with evidence quality to ensure sufficient content validity can aid in burnout evaluation and encourage both expansion of the research field and accurate detection and treatment of this syndrome in Brazilian HCP.


New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications.
This review focuses on the advances in the understanding of the pathophysiology of ventilator-induced and acute lung injury that have been afforded by technological development of imaging methods over the last decades. Examples of such advances include the establishment of regional lung mechanical strain as a determinant of ventilator-induced lung injury, the relationship between alveolar recruitment and overdistension, the regional vs. diffuse nature of pulmonary involvement in acute respiratory distress syndrome (ARDS), the identification of the physiological determinants of the response to recruitment interventions, and the pathophysiological significance of metabolic alterations in the acutely injured lung. Taken together, these advances portray multimodality imaging as the next frontier to both advance knowledge of the pathophysiology of these conditions and to tailor treatment to the individual patient's condition.


Metabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.
Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and abnormalities in the glutamatergic system underlie various CNS disorders. As metabotropic glutamate receptor 3 (mGlu3 receptor) regulates glutamatergic transmission in various brain areas, emerging literature suggests that targeting mGlu3 receptors can be a novel approach to the treatment of psychiatric and neurological disorders. For example, mGlu3 receptor negative allosteric modulators (NAMs) induce rapid antidepressant-like effects in both acute and chronic stress models. Activation of mGlu3 receptors can enhance cognition in the rodents modeling schizophrenia-like pathophysiology. The mGlu3 receptors expressed in the astrocytes induce neuroprotective effects. Although polymorphisms in GRM3 have been shown to be associated with addiction, there is not significant evidence about the efficacy of mGlu3 receptor ligands in rodent models of addiction. Collectively, drugs targeting mGlu3 receptors may provide an alternative approach to fill the unmet clinical need for safer and more efficacious therapeutics for CNS disorders.


Whorled hairless nevus of the scalp, linear hyperpigmentation, and telangiectatic nevi of the lower limbs: a novel variant of the "phacomatosis complex".
The term "phacomatosis" refers to a growing number of sporadic genetic skin disorders characterized by the combination of two or more different nevi and possibly resulting from non-allelic twin spotting. While phacomatosis pigmentovascularis (PPV) and pigmentokeratotica represent the most common patterns, some patients do not fit with either condition and are temporarily classified as unique phenotypes. We report on an 8-year-old boy with striking right hemihypoplasia, resulting in limb asymmetry and fixed dislocation of right hip. Skin on the affected side showed three distinct nevi: (i) A whorled, hairless nevus of the scalp in close proximity with (ii) epidermal hyperpigmentation following lines of Blaschko on the neck and right upper limb, and (iii) multiple telangiectatic nevi of the right lower limb and hemiscrotum. Didymosis atricho-melanotica was proposed for the combination of adjacent patchy congenital alopecia and linear hyperpigmentation, while phacomatosis atricho-pigmento-vascularis appears to define the entire cutaneous phenotype, thus implying the involvement of three neighboring loci influencing the development of distinct constituents of the skin. Given the striking asymmetry of the observed phenotype, the effect of mosaicism (either genomic or functional) for a mutation in a single gene with pleiotropic action and influenced by the lateralization pattern of early development cannot be excluded.


[Paediatric prescribing of anti-asthmatics in primary care in Castilla-León. Geographical variability].
Asthma is one of the most prevalent chronic diseases with effective treatment in paediatrics. The aim of this study is to describe the paediatric prescribing of anti-asthmatics in Castilla-León, analyzing its geographic variability and temporal evolution. An analysis was made of prescriptions dispensed in pharmacies of R03 therapeutic subgroup (anti-asthmatic agents), and the active ingredients mepyramine and ketotifen, prescribed in children less than 14 years of age in the Castilla-León health service from 2005 to 2010 in Primary Care. Data is presented in prescribed daily doses per thousand inhabitants per day (PDHD) for each active ingredient being calculated raw rates and age-adjusted to the variables health area, type of health zone and year of study. A total of 462,354 prescriptions of anti-asthmatic agents were dispensed to a population of 1,580,229 persons/year. There was wide variation between areas in the type and intensity of anti-asthmatic agents used, partly explained by differences in the prevalence of asthma. Montelukast predominated as controller drug in most of them (PDHD 3.1 to 7.7), being similar the consumption intensity in the three types of health zones (PDHD 4.7 to 4.8). The annual variability was low. The study describes the paediatric prescribing pattern of anti-asthmatic agents in Castilla-León between 2005-2010. It shows wide geographical variation, as well as inadequacies regarding current recommendations of asthma treatment.


STIM1 is cleaved by calpain.
Store-operated calcium entry (SOCE) is a pathway that moves Ca(2+) across the plasma membrane and is mediated by two major proteins, STIM1 and Orai1. Here, we discovered that the cytoplasmic domain of STIM1 is a target for calpains, a family of Ca(2+)-activated proteases. We found that calpain cleavage of STIM1 serves to control its cellular abundance and was noticeably increased under conditions of cellular stress and apoptosis. Dysregulation of STIM1 levels has been reported to have human disease consequences and our results suggest a mechanism for controlling STIM1 abundance.


4D radial contrast-enhanced MR angiography with sliding subtraction.
A method is presented for high spatial and temporal resolution 3D contrast-enhanced magnetic resonance angiography. The overall technique involves a set of interrelated components suited to high-frame-rate angiography, including 3D cylindrical k-space sampling, angular undersampling, asymmetric sampling, sliding window reconstruction, pseudorandom view ordering, and a sliding subtraction mask. Computer simulations and volunteer studies demonstrated the utility of each component of the technique. Angiograms of one hemisphere of the intracranial vasculature were acquired with a pixel size of 1.1 x 1.1 x 2.8 mm and a frame rate of 0.35 sec based on a temporal resolution of 3.5 sec. Such a 3D time-resolved, or "4D," technique has the potential to noninvasively acquire diagnostic quality images of certain anatomic regions with a frame rate fast enough to not only ensure the capture of an uncontaminated arterial phase, but even demonstrate contrast bolus flow dynamics. Clinical applications include noninvasive imaging of arteriovenous shunting, which is demonstrated with a patient study.


Crystallization and preliminary crystallographic data for an antiprogesterone monoclonal antibody Fab' and steroid-Fab' complexes.
Crystals of an Fab' from an antiprogesterone monoclonal antibody (IgG1) have been grown from 1.5 M-ammonium sulfate, pH 5.5 to 8.5. The single crystals are hexagonal rods, space group P6222 (or P6422), with cell dimensions a = b = 135.2 A, and c = 124.2 A. Cocrystals of the Fab' with progesterone, pregnanedione and other related steroids have been grown. The complex crystals have different morphology but are isomorphous with the native crystals. A hydroxy-progesterone derivative obtained by substituting an iodo-benzoyl group at the 11 alpha-hydroxyl position looks promising as a suitable heavy-atom candidate in addition to other potential conventional heavy-atom derivatives. All crystals diffract to at least 2.8 A resolution and are suitable for high-resolution X-ray diffraction studies.


Development and survival of free-living stages of gastrointestinal nematodes of sheep and goats on pasture in the Nigerian derived savanna.
Four grass plots were sequentially contaminated with goat faeces containing known numbers of unembryonated eggs of predominantly Haemonchus contortus and Trichostrongylus spp. between October 1982 and April 1983. Four other plots were similarly contaminated with sheep faeces between February and May 1987. An additional plot was repeatedly contaminated with sheep faeces from February to April 1987. Populations of free-living stages in faeces and of infective larvae (L3) in the herbage were subsequently monitored until the end of April and June of 1983 and 1987 respectively. During February and May 1987 two control cultures of sheep faeces were incubated in the laboratory at 25 degrees C-30 degrees C and at a constant temperature of 50 degrees C and the free-living development was also monitored. L3 developed very readily in the faeces cultured at 25 degrees C-30 degrees C and in those spread on a grass plot in October, at the end of the wet season, but developed less on the plot contaminated in May at the start of the wet season. Worm eggs in faeces deposited on plots during the hot dry season (December to April) or incubated at 50 degrees C died and disintegrated after 24-48 h exposure to the high environmental temperatures. The results indicate that it is unlikely that gastrointestinal nematodes of sheep and goats can develop or survive on open pasture during the dry season in the Nigerian derived savanna zone.


L-proline depolarizes rat spinal motoneurones by an excitatory amino acid antagonist-sensitive mechanism.
1 Isolated spinal cords prepared from neonatal rats were used to examine the effects of L-proline (L-Pro). 2 L-Pro (1-8 mM) depolarized ventral and dorsal roots in a dose-dependent manner with one sixth of the potency of L-glutamate (L-Glu). L-Pro was four times more potent than D-Pro. Prolonged application of L-Pro produced a plateau depolarization of motoneurones with no apparent fade. 3 Omission of calcium ions from the medium potentiated the depolarizing actions of L-Pro, L-Glu and quisqualate. 4 L-Pro was antagonized by concentrations of 2-amino-5-phosphonovalerate (25 microM), gamma-D-glutamylglycine (100 microM) and Mg2+ ions (1 mM) that depressed responses to N-methyl-D-aspartate (NMDA). The NMDA receptor-mediated component of the response to L-Pro was estimated to be 60-70%. 5 These data suggest that L-Pro should be considered as a possible excitatory neurotransmitter and that, because L-Pro is a neutral compound, excitatory amino receptors may not require an agonist to possess two anionic groups and one cationic group.


Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and premalignant lesions: association with clinical characteristics.
We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.


Coronary arteriography in acute transmural myocardial infarction.
Coronary arteriography was performed 16 +/- 3 days (range 7 to 21 days) in 106 patients with acute transmural myocardial infarction (61 posterior infarct, 45 anterior infarct). Coronary arteriography was performed without serious complications. Only 44% of patients with anterior infarct had total occlusion of the left anterior descending artery while a significant stenosis of the vessel was observed in the others -27% had a single vessel disease, 49% had two lesions and 22% had three lesions; one patient had angiographically normal coronary arteries. Among the patients with posterior infarction, 21% had one vessel disease and double or triple lesions accounted for 39% of each. Sixty per cent of patients with anterior infarction and 45% with posterior infarction had no collateral vessels. In the others patients collateral circulation had a protective effect only in anterior infarction. Age has no effect on the distribution and number of lesions nor on the development of a collateral circulation. The location and severity of the lesions were not different in patients who presented with arrythmias and those who did not.


Nanoparticle albumin-bound paclitaxel is superior to liposomal paclitaxel in the neoadjuvant treatment of breast cancer.
Aim: The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in neoadjuvant systemic treatment (NST) of breast cancer. Materials & methods: Two hundred thirty-five patients who were diagnosed with invasive breast cancer and then received dose-dense NST with epirubicin and cyclophosphamide followed by paclitaxel were enrolled. Results: Nab-P has an advantage in improving the total and axillary-only pathologic complete response rate over Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In the Lps-P group, the proportion of patients with residual irreversible PSN is larger. Conclusion: Nab-P might be superior to Lps-P in NST of breast cancer.


46 XY undervirulized male DSD: Reporting a patient with prenatally diagnosed disorder/difference of sex development (DSD) with heterozygous LHCGR mutations.
Leydig cell hypoplasia is a rare autosomal recessive condition caused by mutations in luteinizing hormone/chorionic gonadotropin receptor (LHCGR) genes in which 46, XY patients demonstrate a wide spectrum of disorders/differences of sex development (DSD) phenotypes ranging from normal female external genitalia in severe subtypes to micropenis or hypospadias in patients with less severe presentations. Although most patients with LHCGR defects are diagnosed at puberty, here we describe the prenatal diagnosis of 46, XY DSD due to two likely pathogenic variants in LHCGR, one of which has never been reported.


Prospects for overcoming maturational and genetic barriers to the human antibody response to the capsular polysaccharide of Haemophilus influenzae type b.
The isolated capsular polysaccharide induces antibody protective against invasive infections by H. influenzae b. Maturation of responsiveness is slow such that infants are not protected. Several protein-coupled versions of the antigen are being tested for immunogenicity in early infancy. The relation of structure to immunogenicity is not completely defined, but all induce a booster-type antibody response with protective potential. Primary vaccination in infancy appears to mimic natural priming, activating clones of B lymphocytes that can later be restimulated by uncoupled polysaccharide. Prospects appear good for immunizing normal infants and also children with immunoregulatory defects predisposing to infection.


Pericardial effusion and cardiac tamponade requiring pericardial window in an otherwise healthy 30-year-old patient with COVID-19: a case report.
This case report demonstrates pericardial effusion, acute pericarditis, and cardiac tamponade in an otherwise healthy woman who had a positive test result for coronavirus disease 2019. Few case reports have been documented on patients with this presentation, and it is important to share novel presentations of the disease as they are discovered. A Caucasian patient with coronavirus disease 2019 returned to the emergency department of our hospital 2 days after her initial visit with worsening chest pain and shortness of breath. Imaging revealed new pericardial effusion since the previous visit. The patient became hypotensive, was taken for pericardial window for cardiac tamponade with a drain placed, and was treated for acute pericarditis. Much is still unknown about the implications of coronavirus disease 2019. With the novel coronavirus disease 2019 pandemic, research is still in process, and we are slowly learning about new signs and symptoms of the disease. This case report documents a lesser-known presentation of a patient with coronavirus disease 2019 and will help to further understanding of a rare presentation.


Concussion management knowledge among residents and students and how to improve it.
Recognition and management of concussion is an area of growing importance. The objective was to measure concussion knowledge among residents and medical students (MS). Baseline knowledge was assessed by a standardized questionnaire. Control group (family medicine [FM], pediatric medicine [PM] and emergency medicine) residents were given reading material, and intervention group rotated in a clinic (sports medicine residents and MS). Subjects were retested after 36.82 (16.1) days. Pre- and post-intervention test scores were compared. The average baseline knowledge scores were 79.2% for emergency medicine residents, 61.4% for FM, 68.5% for PM, 71.7% for sports medicine residents and 68.0% for MS. Knowledge increase for control group was 1.16% compared with 14.41% for the clinical rotation group (p < 0.0001). PM and FM residents can benefit from more focused education about concussion.


Bladder carcinoma treated by partial cystectomy: a review of 54 cases.
A retrospective study of 54 partial cystectomies done between 1958 and 1973 was undertaken to evaluate the proper role of the procedure in the treatment of bladder carcinoma. The operative mortality rate was 1.8% and the postoperative morbidity was low in the series. The 5-year survival rate for stages B1 (21 cases) and B2 (16 cases) lesions was 57%, with an over-all 5-year survival rate for all stages of 48%. Indications for the operation are presented and factors influencing survival are discussed.


Evasion of host antiviral innate immunity by HSV-1, an update.
Herpes simplex virus type 1 (HSV-1) infection triggers a rapid induction of host innate immune responses. The type I interferon (IFN) signal pathway is a central aspect of host defense which induces a wide range of antiviral proteins to control infection of incoming pathogens. In some cases, viral invasion also induces DNA damage response, autophagy, endoplasmic reticulum stress, cytoplasmic stress granules and other innate immune responses, which in turn affect viral infection. However, HSV-1 has evolved multiple strategies to evade host innate responses and facilitate its infection. In this review, we summarize the most recent findings on the molecular mechanisms utilized by HSV-1 to counteract host antiviral innate immune responses with specific focus on the type I IFN signal pathway.


Wireless signal modulation identification method based on RF I/Q data distribution.
Electromagnetic spectrum detection is the basis of the next generation wireless communication technology. Wireless signal identification is an important part of electromagnetic spectrum detection and management activities. This paper proposes to extract the distribution features of different modulated signals from the signal I/Q data. A two-dimensional gradient matrix is used to describe the characteristics of the signal classification. The minimum gradient cumulative distance (GCD) estimate between the sample and the model is used as the decision criterion for the signal classification. According to the result of the confusion matrix, the weight of the model is adjusted. Experiments show that the recognition rate of the modulated signal mentioned in this paper can reach 82.75%. The I/Q data sample was extracted under actual engineering conditions involving random noise, and the recognition rate dropped to approximately 79%. Based on the initial model gradient matrix, a reasonable algorithm is set to adjust the weight of the model, which can effectively improve the recognition rate of the modulated signal.


Concentration-Dependent Inner Retina Layer Damage and Optic Nerve Degeneration in a NMDA Model.
The intravitreal injection of N-methyl-D-aspartate (NMDA), a glutamate analogue, is an established model for fast retinal ganglion cell (RGC) degeneration. Yet, NMDA does not cause specific RGC damage. Now, the effects on the whole retina were analyzed. Additionally, the related effects for the structure and apoptotic levels of the optic nerve were investigated. Therefore, different NMDA concentrations were intravitreally injected in rats (20, 40, or 80 nmol NMDA or PBS). At days 3 and 14, Brn-3a+ RGCs were degenerated. A damage of calretinin+ amacrine cells was also recognized at day 14. Only a slight damage was observed in regard to PKCα+ bipolar cells, while rhodopsin+ photoreceptors remained intact. A long-lasting retinal microglia response was observed from day 3 up to day 14. Furthermore, a partial degeneration of the optic nerve was noted. At day 3, the SMI-32+ neurofilaments were just slightly affected, whereas the neurofilament structure was further degenerated at day 14. However, the luxol fast blue (LFB)-stained myelin structure remained intact from day 3 up to day 14. Interestingly, apoptotic mechanisms, like FasL and Fas co-localization as well as caspase 3 activation, were restricted to the optic nerve of the highest NMDA group at this late stage of degeneration. The degeneration of the optic nerve is probably only a side effect of neuronal degeneration of the inner retinal layers. The intact myelin structure might form a barrier against the direct influence of NMDA. In conclusion, this model is very suitable to test therapeutic agents, but it is important to analyze all inner retina layers and the optic nerve to determine their efficacy in this model more precisely.


Effect of glucose, sucrose and fructose on plasma glucose and insulin responses in normal humans: comparison with white bread.
To determine the plasma glucose and insulin responses of various doses of glucose, sucrose, fructose and white bread in normal human subjects. Plasma glucose and insulin were measured before and at various times after 8 subjects ate 13 different test meals in randomized order on separate days after an overnight fast. Test meals consisted of 500 ml of tea or water to which was added either nothing, 25, 50, or 100 g of glucose or sucrose, 25 or 50 g fructose, 50 g glucose plus 50 g fructose, or a 25, 50 or 100 g carbohydrate portion of white bread. The glycaemic (GI) and insulinaemic index (II) values of the sugars were calculated by expressing the incremental areas under the plasma glucose and insulin curves (AUC) after glucose, sucrose and fructose as a percentage of the respective AUC after white bread containing the same amount of carbohydrate. University teaching hospital clinical nutrition centre. Lean, normal subjects (4 male, 4 female) 21-33 y of age. Plasma insulin responses increased nearly linearly as carbohydrate intake increased from 0 to 100 g, but glycaemic responses increased by only 68% and 38% as carbohydrate intake increased from 25 to 50 g and 50 to 100g, respectively. The GI and II values of glucose, 149+/-16 and 147+/-18, respectively, were significantly greater than those of bread (100; P<0.05), while the values for fructose, 16+/-4 and 22+/-3 were significantly less than those of bread (P<0.001). GI values did not differ significantly from II values. It is concluded that, in normal subjects, as carbohydrate intake is increased from 0 to 100 g, plasma insulin responses increase at a greater rate than plasma glucose responses. The insulinaemic responses elicited by glucose, sucrose or fructose are similar to those that would be expected from a starchy food with the same glycaemic index.


Prognostic significance of forced vital capacity decline prior to and following antifibrotic therapy in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease (ILD). Currently, two antifibrotic drugs are available for reducing forced vital capacity (FVC) decline in IPF. However, many pulmonologists wait before initiating treatment, especially when IPF patients have stable disease. This study aimed to investigate the impact on survival outcome of FVC decline and a slow rate of FVC decline prior to and following treatment with these two antifibrotic drugs. Out of the 235 IPF patients treated with antifibrotic therapy that were screened, 105 cases were eligible, who then underwent physiological evaluation at 6 months prior to and following antifibrotic therapy. Clinical characteristics and prognostic outcomes were compared among groups, and prognostic factors were evaluated using a Cox proportional hazards analysis. In terms of %FVC decline prior to the therapy and a slow rate of FVC decline, there was no significant difference between stable and worsened groups and responder and non-responder groups, respectively. On the other hand, in terms of %FVC decline (decline >5%) following antifibrotic therapy, the stable/improved group had significantly better prognosis than the worsened group. Prognostic analysis revealed that a stable/improved status following antifibrotic therapy [HR: 0.35 (0.15-0.87)] was significantly associated with a better prognosis. Concerning the FVC decline prior to and following antifibrotic therapy and a slow rate of FVC decline, only the FVC decline following the therapy is associated with a greater survival outcome. An early treatment decision may thus be beneficial for IPF.The reviews of this paper are available via the supplemental material section.


Biochemical mapping of the noradrenergic ventral bundle projection sites: evidence for a noradrenergic--dopaminergic interaction.
Norepinephrine (NE) and dopamine (DA) concentration and dopamine turnover were measured 12 days after a unilateral or bilateral noradrenergic ventral bundle (VB) transection to determine the noradrenergic projection sites and possible interactions with dopaminergic systems. Both bilateral and unilateral VB transection resulted in a significant reduction of NE of the nucleus accumbens, lateral septal nucleus, medial forebrain bundle, ventromedial nucleus, dorsomedial nucleus and medial amygdaloid nucleus. Bilateral transection also decreased NE content of the median eminence and the periventricular and arcuate nuclei. In the medial preoptic nucleus, the nucleus interstitialis striae terminalis and the central gray catecholamine area, bilateral transection significantly decreased NE concentrations while unilateral lesions had no significant effect. The anterior hypothalamic, lateral preoptic, and paraventricular nuclei responded to bilateral VB transection with a decrease in NE concentration and to unilateral lesion with a bilateral increase in NE. In the dorsal hippocampus and the caudate nucleus, bilateral lesions had no effect on NE concentrations while unilateral transection significantly decreased NE concentrations. Regions in which neither bilateral nor unilateral VB transection produced a significant change in NE content are the olfactory tubercle, the nucleus tractus diagonalis, substantia nigra pars compacta and reticulata, ventral tegmental area, habenula, superior colliculus, and the cingulate and piriform cortices. Transection of the noradrenergic ventral bundle also produced changes in dopaminergic systems suggesting a noradrenergic--dopaminergic interaction. Bilateral VB transection decreased the dopamine concentration and turnover in the nucleus accumbens, increased steady-state levels and turnover in the nucleus tractus diagonalis and increased dopamine concentration in the lateral septum. Unilateral VB transection decreased DA concentration bilaterally in the caudate nucleus, olfactory tubercle, nucleus accumbens and the nucleus interstitialis striae terminalis but increased concentrations in the substantia nigra pars reticulata (ipsilateral) and in the ventral tegmental area (bilateral). These results indicate a broad projection field for the noradrenergic ventral bundle and suggest a noradrenergic--dopaminergic interaction.


Efficacy of permanent gastric electrical stimulation for the treatment of gastroparesis and functional dyspepsia in children and adolescents.
Permanent gastric electrical stimulation (GES) has been performed in adults as a treatment for gastroparesis and refractory nausea and vomiting in patients who have failed medical therapy. We assessed the feasibility and clinical outcomes of permanent GES in children. Permanent GES was performed in 16 children (10 females/6 males), median age 15 years (range 4-19 years). All patients had chronic nausea and vomiting refractory to medical therapy and met ROME III criteria for functional dyspepsia. Symptoms, route for nutrition, and satisfaction with procedure were recorded before and after permanent GES. Statistical analysis was performed using paired Student's t test. After permanent GES, there was significant improvement in severity of vomiting (p=0.0001), frequency of vomiting (p=0.0003), frequency of nausea (p<0.0001), and severity of nausea (p<0.0001). At the time of follow-up, 13/16 were on oral feeds exclusively, two patients on oral plus G-tube feedings, and one patient on oral plus G-tube plus intermittent TPN. 1). Permanent GES improved health in children with functional dyspepsia and gastroparesis who fail medical therapy. 2). No serious adverse effects of permanent GES were noted. 3). Long-term efficacy and safety of GES therapy in children need to be established.


Prospective study on the treatment of lower-extremity chronic venous and mixed ulcers using tissue-engineered skin substitute made by the self-assembly approach.
Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers. The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient's own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution. Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care. The authors' study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.


Differentiating Motivational from Affective Influence of Performance-contingent Reward on Cognitive Control: The Wanting Component Enhances Both Proactive and Reactive Control.
Positive affect strongly modulates goal-directed behaviors and cognitive control mechanisms. It often results from the presence of a pleasant stimulus in the environment, whether that stimulus appears unpredictably or as a consequence of a particular behavior. The influence of positive affect linked to a random pleasant stimulus differs from the influence of positive affect resulting from performance-contingent pleasant stimuli. However, the mechanisms by which the performance contingency of pleasant stimuli modulates the influence of positive affect on cognitive control mechanisms have not been elucidated. Here, we tested the hypothesis that these differentiated effects are the consequence of the activation of the motivational "wanting" component specifically under performance contingency conditions. To that end, we directly compared the effects on cognitive control of pleasant stimuli (a monetary reward) attributed in a performance contingent manner, and of random pleasant stimuli (positive picture) not related to performance, during an AX-CPT task. Both proactive and reactive modes of control were increased specifically by performance contingency, as reflected by faster reaction times and larger amplitude of the CNV and P3a components. Our findings advance our understanding of the respective effects of affect and motivation, which is of special interest regarding alterations of emotion-motivation interaction found in several psychopathological disorders.


Incubation energetics of the Laysan Albatross.
The energy expenditure of incubating and foraging Laysan Albatross (Diomedea immutabilis, mean body weight 3.07 kg) was estimated by means of the doubly-labelled water technique. During incubation, the energy expenditure was similar to that of resting birds that were not incubating an egg. The energy expenditure of foraging albatross (2072 kJ/day) was 2.6 times that of resting birds. It was concluded that the energy expenditure of the tropical Laysan Albatross was not less than that of species foraging over cold, high-latitude oceans. An energy budget compiled for an incubating pair of albatross revealed that the energy expenditure of the female was greater than that of the male bird, during the incubation period.


Basal production of nitric oxide (NO) and non-NO vasodilators in the forearm microcirculation in Type 2 diabetes: associations with blood pressure and HDL cholesterol.
We examined basal forearm microcirculatory blood flow (FBF) using venous occlusive strain-gauge plethysmography in 47 middle-aged men and women [55+/-1 years] with Type 2 diabetes and 15 age-matched healthy individuals [52+/-3 years], all receiving aspirin. Blood flow was also measured following infusion of N(G)-monomethyl-L-arginine into the brachial artery to inhibit basal NO release (FBF+L-NMMA). Acetylcholine (ACh) and sodium nitroprusside (SNP) were administered to assess endothelium-dependent and endothelium-independent functions. Compared with controls, diabetic subjects had significantly lower vasodilatory responses to ACh and SNP (p<0.05 for each). Basal FBF and FBF+L-NMMA were increased in diabetic subjects compared with controls (2.4+/-0.2 ml/100ml/min versus 1.7+/-0.2 ml/100ml/min, p=0.02 and 1.9+/-0.1 ml/100ml/min versus 1.2+0.1 ml/100ml/min, p=0.01, respectively) whereas the change in FBF following L-NMMA was greater in the controls (-27% versus -19%, p=0.05). Amongst the diabetic subjects, pulse pressure and HDL cholesterol were independent predictors of FBF (b=0.04+/-0.01, adjusted r2=0.21 and p=0.001, and b=3.3+/-1.2, adjusted r2=0.12 and p=0.007, respectively) and FBF+L-NMMA (b=0.03+/-0.01, adjusted r2=0.20, p=0.002 and b=2.1+/-0.9, adjusted r2=0.09 and p=0.02, respectively). Diastolic blood pressure predicted the change in FBF with L-NMMA (b=-1.02+/-0.32, adjusted r2=0.20 and p=0.003). Our findings suggest that well controlled T2DM patients have impaired agonist-mediated vasodilatation of the forearm resistance arteries that is associated with impaired basal release of nitric oxide but an increase in the release of non-NO vasodilators. The latter may be a compensatory response to increased arterial stiffness and may be facilitated by an effect of HDL.


A new liver functional study using Tc-99m DTPA-galactosyl human serum albumin: evaluation of the validity of several functional parameters.
Several parameters calculated with a new functional imaging agent for the liver, Tc-99m DTPA-galactosyl human serum albumin, were evaluated in 9 patients with liver cirrhosis, one with hepatocellular carcinoma, and five with both liver cirrhosis and hepatocellular carcinoma. LU3, which represents the cumulative uptake of the tracer from 3 to 4 minutes after injection, showed a strong correlation (r = 0.858, p = 0.0001) with LHL15, which represents the count ratio for the liver to sum for the liver and heart 15 minutes after injection of the tracer. It also showed a strong correlation (r = -0.896, p = 0.0001) with the indocyanine green retention rate (ICGR15). Regional ICGR15 is therefore calculable from the regional LU3. GSAR15, which represents the radioactivity of the tracer retained in the blood 15 minutes after injection, showed a strong correlation (r = 0.878, p = 0.0001) with HH15, which represents the count ratio for the heart 15 minutes after injection of the tracer divided by the count for the heart 3 minutes after injection. In conclusion, LU3 and GSAR15 are interesting and promising parameters for assessing liver function.


Comparison of non-protected lower respiratory tract secretions and protected specimen brush samples in the diagnosis of pneumonia.
The aim of this prospective study was to compare the results obtained with the non-protected lower respiratory tract secretions samples (LRS) with the protected specimen brushes (PSB) performed through a fiberoptic bronchoscope in mechanically ventilated patients, when pneumonia was suspected. The diagnosis of pneumonia was ultimately made at the end of the hospitalisation, in a double-blind manner by 2 members of the medical staff not aware of the bacteriologic results of LRS and PSB. LRS and PSB were performed in 24 patients. PSB culture was considered as positive at a level of 10(3) colony-forming units per milliliter (cfu/ml) microorganisms. Twenty-five samples from 24 patients were divided as follows: (1) LRS (-) and PSB (-) 5 samples: the clinical diagnosis of pneumonia was never established. (2) LRS (+) and PSB (+) 10 samples: the clinical diagnosis of pneumonia was always established, 2 microorganisms were involved 4 times and 1 microorganism 6 times. (3) LRS (+) and PSB (-) 10 samples: the clinical diagnosis pneumonia was retained in 3 with the possibility of false negative PSB. We conclude that (1) a negative LRS eliminated the diagnosis of pneumonia without PSB; (2) a positive LRS was not sufficient to diagnose pneumonia since PSB was negative in 50% of all LRS (+) cases; (3) the possibility of a false negative PSB must be kept in mind particularly in patients previously treated with antibiotics; (4) 2 microorganisms may be responsible for the pneumonia if the previously determined, as significant, bacteriological count (greater than or equal to 10(3) cfu/ml) appears to be accurate.


A 6-hydroxydopamine in vivo model of Parkinson's disease.
Animal models of Parkinson's disease are essential to explore pathophysiological hypotheses and to test new treatment options, including neurotrophic factors. Catecholaminergic neurotoxins used to generate such models are 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These neurotoxins predominantly kill dopaminergic neurons through oxidative damage and mitochondrial failure, although 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine fails to induce a significant dopaminergic neurodegeneration in rats. The present chapter describes a protocol for the 6-hydroxydopamine rat model based on stereotaxic injection performed only unilaterally, which mimics an early-to-mid stage of the disease.


Contribution of Reproduction Management and Technologies to Genetic Progress in Horse Breeding.
Reproductive technologies aim at improving fertility with the ultimate result of improving genetic selection. In equidae, the respective contribution of different methods of horse management and breeding to genetic progress remain difficult to evaluate as breeding strategies affect the number of offspring per mare or stallion whereas different selection methods (based on pedigree, performance, genomics or progeny's performance) will be applicable at different ages, leading to different accuracy in the estimation of the breeding value. Here, a mathematical model was applied to evaluate theoretical genetic progress depending on breeding conditions in horses. The model showed that for breeding systems ranging from 0.6 to 2 foals/year/mare and from 10 to 150 foals/year for stallions, when selection of the best animals is strictly made by a truncation, the genetic progress is accelerated by (1) increasing the number of offspring per year, (2) the start of reproduction as soon as the age of 2 in both sexes, and (3) reducing the number of years of use for stallions from 10 to 5 years. The calculation showed that using all ways of improvement could provide an increase in genetic progress of up to +270% and +226% in mares and stallions, respectively, above the basal reference situation of 100%. In the Selle Français breed, the observed reproductive management parameters (10 years generation interval, 10 foals/stallion and 0.55 foals/mare) are close to the worst conditions of the model. In addition, the best mares are not selected for breeding. In conclusion, new reproductive technologies, genomic selection, and breeding younger animals will increase genetic gain.


Genetic mapping of craniofacial traits in the Mexican tetra reveals loci associated with bite differences between cave and surface fish.
The Mexican tetra, Astyanax mexicanus, includes interfertile surface-dwelling and cave-dwelling morphs, enabling powerful studies aimed at uncovering genes involved in the evolution of cave-associated traits. Compared to surface fish, cavefish harbor several extreme traits within their skull, such as a protruding lower jaw, a wider gape, and an increase in tooth number. These features are highly variable between individual cavefish and even across different cavefish populations. To investigate these traits, we created a novel feeding behavior assay wherein bite impressions could be obtained. We determined that fish with an underbite leave larger bite impressions with an increase in the number of tooth marks. Capitalizing on the ability to produce hybrids from surface and cavefish crosses, we investigated genes underlying these segregating orofacial traits by performing Quantitative Trait Loci (QTL) analysis with F2 hybrids. We discovered significant QTL for bite (underbite vs. overbite) that mapped to a single region of the Astyanax genome. Within this genomic region, multiple genes exhibit coding region mutations, some with known roles in bone development. Further, we determined that there is evidence that this genomic region is under natural selection. This work highlights cavefish as a valuable genetic model for orofacial patterning and will provide insight into the genetic regulators of jaw and tooth development.


Effect of sexual dimorphism in bill length on foraging behavior: an experimental analysis of hummingbirds.
We examined whether sexual differences in trophic morphology are associated with sexual differences in foraging behavior through two laboratory experiments on rufous hummingbirds (Selasphorus rufus) designed to compare probing abilities (maximum extraction depths) and handling times of sexes at flowers. Bills of female S. rufus are about 10.5% longer than bills of males, and this difference was associated with sexual differences in foraging abilities. Maximum extraction depths of female S. rufus were significantly greater than those of males, and no overlap between the sexes was observed. Moreover, handling times of females were shorter than handling times of males at flowers having longer corollas (≥15 mm). Thus, because of their longer bills, female S. rufus have the potential to feed from longer flowers than males, and can do so more quickly. We suggest that no single mechanism is responsible for the evolution of sexual dimorphism in bill lengths of hummingbirds, but rather that the dimorphism probably reflects the combined effects of reproductive role division and intersexual food competition, and possibly, sexual selection.


Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat.
In vivo experiments were performed in male Wistar rats to elucidate the probable relation between renal concentrating ability and medullary cyclic AMP content as influenced by changes of hydration and by administration of antidiuretic hormone (ADH). Cyclic AMP levels were 37% lower in water diuretic than in control animals (P less than 0.01), but were not significantly changed during prolonged antidiuresis induced by dehydration or ADH administration. Nor could any change of cyclic AMP levels be demonstrated between 2 and 20 min after ADH injection. Significant increases of medullary cyclic AMP content occurred following stress, anesthesia, and administration of isoproterenol and 3-isobutyl-1-methylxanthin. The results suggest that the level of cyclic AMP in the renal medulla may not be an important determinant of the antidiuretic response produced by ADH in rats.


Continuous lumbar plexus block provides improved analgesia with fewer side effects compared with systemic opioids after hip arthroplasty: a randomized controlled trial.
A single injection lumbar plexus block for acute pain management after hip surgery is usually limited to the immediate postoperative period. We conducted a randomized controlled trial to determine the effect of a continuous lumbar plexus block on perioperative opioid requirements and pain intensity. Adult patients undergoing elective hip arthroplasty under general anesthesia were randomized to continuous lumbar plexus block combined with patient-controlled analgesia (PCA) or PCA only for postoperative pain. Patients allocated to the lumbar plexus block had the catheter placed before surgery. Patients were followed for 36 hours. Perioperative opioid requirement was the primary outcome; secondary outcomes included assessment of pain intensity, patient and surgeon satisfaction with the analgesic technique, and occurrence of nausea and vomiting. Seventeen patients were randomized to each treatment group. Compared with patients in the PCA group, patients in the continuous lumbar plexus block group required less morphine (12 mg) (95% CI, -12.9 to -3.9), had on average less pain (-2.1 units on a 0 to 10 scale) (95% CI, -3.8 to -1.1), were more satisfied with their analgesic technique, and experienced less nausea and vomiting. One patient in the continuous lumbar plexus block developed a delayed paresis and 1 patient in the PCA group developed respiratory depression. Continuous lumbar plexus block combined with PCA is superior to PCA alone for postoperative pain management following hip replacement. It reduces opioid requirements, opioid related side effects, and enhances patient satisfaction. However, additional research is required to determine its safety in light of the neurologic injury observed.


Extent of alkaline phosphatase cytochemistry vs. extent of tetracycline fluorescence in the evaluation of histodynamic variables of bone formation.
Alkaline phosphatase (ALP) activity is a new histomorphometric index of the extent of osteoblastic surfaces involved in mineralization. To assess its validity in the evaluation of bone formation, we carried out a comparative study between histomorphometric values obtained on the basis of the extent of tetracycline labeling and of the length of ALP-positive endosteal surfaces. The following variables were compared (indicated by ALP when based on the extent of ALP positivity): trabecular mineralizing surface (MS/BS vs. ALP.S/BS); osteoid mineralizing surface (MS/OS vs. ALP.S/OS); bone formation rate (BFR/BS vs. ALP.BFR/BS); and adjusted appositional rate (Aj.AR vs. ALP.Aj.AR). Bone biopsies from 39 patients with chronic renal failure and different types of renal osteodystrophy were considered (48 +/- 12 years of age; 19 men and 20 women). Patients were double labeled with tetracycline and biopsies were embedded in glycol-methacrylate at +4 degrees C. Patients showed various types of renal osteodystrophy and were assigned to different groups of pathologies. Although it differed in incidence according to the different groups, ALP activity was found in typical plump osteoblasts bordering osteoid seams and in flat cells, either in contact with osteoid or along the quiescent surfaces of bone in continuity with it. Tetracycline codistributed with all these features to variable extents, according to groups. In all patients, however, ALP.S/BS and ALP.S/OS respectively exceeded MS/BS and MS/OS. In consequence of this, ALP.BFR/BS and ALP.Aj.AR were greater than BFR/BS and Aj.AR, respectively. For each of the variable considered, differences among groups of patients with different types of renal osteodystrophy were highly significant. Good correlations were found between the variables measured with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)


Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19. Four agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. TICO utilizes a MAMS design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo as well as the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and DSMB schedule was developed for the study of agents with limited in-human data. Challenges included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff, and obtaining regulatory approvals across a global network of sites. Through a robust multi-network partnership, the TICO protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required.


Incidence of tinnitus, impaired hearing and musculoskeletal disorders among students enrolled in academic music education--a retrospective cohort study.
The aim was to determine the incidence of tinnitus, impaired hearing and musculoskeletal disorders among musicians and the relation to the number of practicing hours and/or the instrument type before the onset of symptoms. The study base consisted of students enrolled in the School of Music and Music Education at Göteborg University between the years 1980 and 1995. There were 407 of the 602 original students that answered a questionnaire (response rate of 68%). The questionnaire concerned exposure before and after the enrollment in the Music Academy, as well as onset of symptoms. The highest incidence of symptoms was found for reported tinnitus with a rate of 10.6 per 1000 years of instrumental practice. There was a relationship between exposure to the number of hours of instrumental practice and incidence of impaired hearing. Among the musculoskeletal symptoms the highest incidences per 1000 years of instrumental practice were pain in the neck and in the left shoulder with a rate of 4.4 and 4.6 disorders per 1000 years of instrumental practice, respectively. There was 2.4 times higher incidence for musculoskeletal disorders in the right hand/wrist and a 2.2 times higher incidence in the left elbow/forearm for musicians who practiced for 20 h or more per week before the onset of disorders compared to those who practiced fewer than 20 h per week when controlling for age and gender. Musicians with a violin or a viola as the main instrument had four times the incidence for right elbow/forearm disorder and twice the incidence of neck pain, pain in the right shoulder and the left elbow/forearm compared to those who had piano as the main instrument.


The effects of Roux-en-Y gastric bypass surgery on body image.
Numerous studies examine the physical effects of Roux-en-Y gastric bypass (RYGBP) surgery on morbid obesity. However, the effects of this surgery on psychosocial issues such as body image have not been extensively studied. This pilot study used a cross-sectional design to examine the effects of RYGBP surgery on patients' perceived body image. Four groups (n = 20) were assessed for perceived change in body image at 4 time intervals. These included pre-surgery, 1 to 3 weeks post-surgery, 6-months post-surgery, and 1-year post-surgery, with two measures of body image. One-way ANOVA was applied, with body image measures as the dependent variables, and time since surgery (group) as the independent variable. Planned post-hoc t-tests were applied to assess the differences between specific groups (pre vs. 1 week, pre vs. 6 months post, 6 months post vs. 1 year post). Results of the one-way ANOVAs revealed significant improvement on perceptions of body image over time following surgery. Follow-up t-tests revealed that the most significant improvement occurred between pre-surgery and 6 months post-surgery. Although smaller, the change between 6 months post-surgery and 1 year post-surgery was also significant. While RYGBP results in numerous medical and physical benefits, this study reveals that there are also dramatic improvements in perceived body image, demonstrating the impact of this surgery on a patient's psychosocial health.


Assessment of reasons for not intensifying antihypertensive treatment in the Taiwanese population.
Despite availability of effective antihypertensives, blood pressure (BP) control is usually inadequate. The Reasons for not Intensifying Antihypertensive Treatment (RIAT) registry evaluated the reasons behind not modifying treatment in an international, cross-sectional study in 16 countries. The Taiwanese cohort of RIAT consisted of 8922 patients with untreated/uncontrolled essential hypertension recruited from 22 centers in the country. At the first visit, physicians selected target BP and antihypertensive treatment, and at the next three visits they measured BP and modified treatment/provided justification for not modifying treatment. Mean target BP selected by physicians was 134.6/84.6 ± 5.1/5.0 mmHg, respectively. Patients' individual risk stratification determined the BP goals. More patients achieved targets according to the physicians' opinion than based on actual BP measurements: visit 2-50.6% vs. 48.6%; visit 3-58.4% vs. 55.2%; and visit 4-61.2% vs. 57.0%. At each visit, treatment remained unchanged for >60% patients not reaching target; the most common reason for this at visit 2 was the assumption that the time was too short to assess new drug therapy and at visits 3 and 4 was the assumption that target was reached/had almost been reached. About 40% Taiwanese hypertensive patients in RIAT did not reach BP targets after an average of 4 months' follow-up. The most common reason for not modifying treatment was the assumption that the target had been reached or had almost been reached.


miR548ai antagonism attenuates exosome-induced endothelial cell dysfunction.
Endothelial cell (EC) and smooth muscle cell (SMC) are major cell types adjacent in the vascular wall. Recent progress indicates that their communication is crucial for vascular homeostasis and pathogenesis. In particular, dysfunctional (proliferative) SMCs through exosomes can induce EC dysfunction (impaired growth). The current study suggests that miR548ai, a rarely known microRNA, may provide a molecular target for protection against SMC/exosome-induced EC dysfunction. We performed microarray profiling of microRNAs of dysfunctional human primary aortic SMCs induced by different cytokines (PDGF-BB, TGFβ1, TNFα, IL1β). Among the microRNAs commonly upregulated by these cytokines, miR548ai showed the most robust changes, as also validated through quantitative PCR. This cytokine-induced miR548ai upregulation was recapitulated in the qPCR determination of SMC-derived exosomal microRNAs. Consistent with SMC-to-EC communication, the exosomes extracted from cytokine-stimulated SMCs impaired human EC proliferation and migration. Of particular interest, this SMC exosomal impingement on ECs was countered by transfection of miR548ai inhibitor microRNA into ECs. Furthermore, the miR548ai inhibitor transfected into SMCs attenuated SMC dysfunction/proliferation. Thus, these results identify miR548ai as a novel target; namely, miR548ai inhibitor mitigates EC dysfunction induced by exosomes derived from dysfunctional SMCs. This new knowledge may aid the future development of microRNA-based treatment of vascular disorders.


Outbreak of Trichophyton soudanense causing tinea capitis in an orphanage in Myanmar.
We report an outbreak of Trichophyton soudanense causing tinea capitis and corporis in an orphanage in Myanmar. The thirty orphan children were suspected to have anthropophilic tinea but zoonotic tinea could not be excluded as all children were playing with stray dogs. Direct mycological examinations of hair and scalp samples showed filaments but culture assays remained sterile. We revealed T. soudanense as the infectious agent by PCR amplification of extracted fungal DNA and further sequencing of the PCR products. Children were successfully treated by terbinafine and reinfection was prevented by hygiene measures. This case report shed the light on T. soudanense infection on another continent than Africa and on the significant help of PCR identification.