[The changes of natural resistance of the patients with acute adhesive ileus].
The state of an organism natural resistance before and after the operative intervention for an acute adhesive ileus (AAI) was investigated. There was established, that the natural resistance of organism persisting after the operative intervention conduction constitutes the diagnostic criterion of the adhesive process progression in abdominal cavity and of the AAI recurrence occurrence.


Expression and regulation of basic fibroblast growth factor mRNA levels in mouse osteoblastic MC3T3-E1 cells.
Basic fibroblast growth factor (bFGF) is a potent mitogen for bone cells and is a constituent of the bone matrix. We have found that osteoblastic MC3T3-E1 cells expressed bFGF mRNA transcript of 4.5 kilobases (kb). We examined factors that regulate the expression of bFGF mRNA and protein in MC3T3-E1 cells. Treatment of MC3T3-E1 cells with bFGF (10 nM) for 4-48 h induced another 7-kb bFGF transcript at 4 h. Treatment of MC3T3-E1 cells with TGF beta (10 ng/ml) also induced the 7-kb transcript of bFGF mRNA. In contrast, heparin, parathyroid hormone, and interleukin-1 had no effect on bFGF mRNA. Western blot analyses revealed that MC3T3-E1 cells produced a 24-kDa bFGF protein, which was increased by TGF beta. Immunofluorescence showed that bFGF protein was localized to the cytoplasm in serum-deprived MC3T3-E1 cells. Treatment of these cultures with medium containing fetal calf serum or TGF beta caused increased cytoplasmic staining for bFGF and marked shape change. Furthermore, in the cells treated with TGF beta there was both nuclear and cytoplasmic staining for the protein. These data demonstrate that bFGF mRNA and protein are expressed in osteoblastic cells and are regulated by treatment with TGF beta and bFGF. Production of bFGF may be important as an autocrine and paracrine mediator of bone cell replication, differentiation, and function.


Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme.
Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone.


The magnesium load test: experience in elderly subjects.
While serum magnesium is the simplest and most widely used approach to the evaluation of magnesium status, it is recognized that a normal serum level can occur in the presence of tissue depletion. The magnesium load test is a reliable indirect method of assessing whole body magnesium status, but experience with its use in older subjects is limited. The initial aim was to establish a range of results for the magnesium load test in older subjects who were likely to be tissue depleted. Such data would enable more accurate interpretation of the test in older subjects with normal serum levels who might be tissue-magnesium depleted. Magnesium loading was performed in 43 female subjects, average age 83 years, with serum magnesium levels not exceeding 0.75 mmol/l (mean 0.63 +/- 0.09 mmol/l) and lower than recommended dietary magnesium intakes. Magnesium sulphate was given intravenously, 0.25 mmol magnesium/kg body weight at a rate of 2.5 mmol/hour. Twenty-four-hour urine magnesium was determined for two days before the test and on the day of test from the start of the infusion. The test was abandoned in 13 other subjects because it was not possible to obtain three consecutive accurate urine collections despite careful selection. In the remaining 30 subjects, average magnesium retention was 62% (range 15-98%). Serum magnesium appeared a better guide to tissue status than urine magnesium, but creatinine clearance correlated better with the degree of magnesium retention than either serum or urine magnesium levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Osmoregulation and contractile vacuoles of protozoa.
Protozoa living in fresh water are subjected to a hypotonic environment. Water flows across their plasma membrane since their cytosol is always hypertonic to the environment. Many wall-less protozoa have an organelle, the contractile vacuole complex (CVC), that collects and expels excess water. Recent progress shows that most, if not all, CVCs are composed of a two-compartment system encircled by two differentiated membranes. One membrane, which is often divided into numerous vesicles and tubules, contains many proton-translocating V-ATPase enzymes that provide an electrochemical gradient of protons and which fuses only with the membrane of the second compartment. The membrane of the second compartment lacks V-ATPase holoenzymes, expands into a reservoir for fluid storage, and is capable of fusing with the plasma membrane. It is this second compartment that periodically undergoes rounding ("contraction"), setting the stage for fluid expulsion. Rounding is accompanied by increased membrane tension. We review the current state of knowledge on osmolarity, ion concentrations, membrane permeability, and electrophysiological parameters of cells and their contractile vacuoles, where these criteria are helpful to our understanding of the function of the CVC. Effects of environmental stresses on the CVC function are also summarized. Finally, other functions suggested for CVCs based on molecular and physiological studies are reviewed.


Iatrogenic diaphragmatic hernia complicating nephrectomy: top-down or bottom-up?
Hernias of the diaphragm are rarely reported as a complication of abdominal surgery. We review a case of a 47-year-old female who presented with dyspnoea and chest pain one day after left radical nephrectomy for renal cell carcinoma. Plain and cross-sectional imaging identified a large left-sided diaphragmatic hernia containing omentum, spleen, splenic flexure, and stomach. Our patient underwent a thoracotomy and, after hernia reduction, the diaphragmatic defect was repaired using non-absorbable sutures and a mesh. She made an uneventful recovery. The potential cause is discussed and the published literature on this rare complication is reviewed briefly.


Management of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a deadly progressive lung disease without an effective standard treatment approach. Because of the complexity and uncertainties of IPF treatment, therapeutic decisions need to be tailored to the individual patient, after discussing the potential benefits and pitfalls. Pirfenidone has been approved for the treatment of IPF in many countries, but is not recommended as a first-choice therapy by current guidelines because of the lack of a definite efficacy. Randomized controlled trials represent a valid choice for patients with IPF, and their completion is important in improving both survival and quality of life.


Yakubovich's oscillatority of circadian oscillations models.
The testing procedure of Yakubovich's oscillatority property is presented. The procedure is applied for two models of circadian oscillations [J.C. Leloup, A. Goldbeter, A model for circadian rhythms in Drosophila incorporating the formation of a complex between the PER and TIM proteins, J. Biol. Rhythms, 13 (1998) 70-87; J.C. Leloup, D. Gonze, A. Goldbeter, Limit cycle models for circadian rhythms based on transcriptional regulation in Drosophila and Neurospora. J. Biol. Rhythms, 14 (1999) 433-448]. Analytical conditions of these models oscillatority are established and bounds on oscillation amplitude are calculated.


Identification of Driver Genes and Key Pathways of Glioblastoma Shows JNJ-7706621 as a Novel Antiglioblastoma Drug.
The aim of this study is to identify novel targets of diagnosis, therapy, and prognosis for glioblastoma, as well as to verify the therapeutic effect of JNJ-7706621 regarding glioblastoma. The gene expression profiles of GSE42656, GSE50161, and GSE86574 were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified with comparison between gene expression profiles of the glioblastoma tissues and normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were performed. Quantitative reverse transcription polymerase chain reaction and survival curve analysis were also conducted to verify the correlation between expression of hub genes and prognosis. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay, and flow cytometry were performed to verify the therapeutic effect of JNJ-7706621. AURKA, NDC80, KIF4A, and NUSAP1 were identified as hub genes after PPI network analysis. Differential expression of those genes was detected between human normal glial cells and glioblastoma cells by quantitative reverse transcription polymerase chain reaction (P < 0.05), and the survival curve analysis showed that the patients with low expression of gene AURKA, NDC80, KIF4A, and NUSAP1 had a significant favorable prognosis (P < 0.05). In vitro assays showed that JNJ-7706621 inhibited glioblastoma cellular viability, proliferation, and migration via inducing glioblastoma cells apoptosis. AURKA, NDC80, KIF4A, and NUSAP1 were significantly more highly expressed in glioblastoma cells than in human normal glial cell. Patients with low expression of those 4 genes had a favorable prognosis. JNJ-7706621 was a potential drug in treatment of patients with glioblastoma.


The effects of nicotine on the attentional modification of the acoustic startle response in nonsmokers.
Research on nicotine and attention has mainly utilized samples of deprived smokers and tasks requiring volitional responses, raising the question of whether nicotine improves attention or simply alleviates withdrawal or improves motor speed. This study used the startle eyeblink reflex to assess nicotine effects on auditory attention in nonsmokers. Sixty-seven healthy young adult nonsmokers completed a tone discrimination task. Acoustic startle probes were presented 60, 120, 240, or 4,500 ms after the onset of two-thirds of the tones and during intertrial intervals. Attention was assessed via (1) short-lead prepulse inhibition (PPI) of startle, a measure of early filtering; (2) long-lead prepulse facilitation (PPF) of startle, a measure of sustained processing; and (3) the modification of PPI and PPF by focused attention. Participants completed two laboratory sessions, once while wearing a 7-mg transdermal nicotine patch and once while wearing a placebo patch. Patches were administered in a double-blind procedure. Nicotine increased overall PPI, eta2(p)=0.09. Attention increased long-lead PPF, eta2(p)=0.25, but not short-lead PPI. Nicotine did not reliably enhance early or late controlled attentional processing in the sample overall. However, correlational analyses demonstrated that nicotine most improved attentional modification of short-lead PPI among participants with the weakest early attentional processing under placebo conditions. Nicotine enhanced early attentional filtering in general, and the effects of nicotine on early focused attention were dependent upon individual differences in placebo levels of attentional processing. The present data suggest that the effects of nicotine on attention extend beyond the alleviation of withdrawal and simple motor speeding.


Preschoolers' choices of television characters as sources of information: Effects of character type, format, and topic domain.
Educational television (TV) for preschoolers often features unrealistic (anthropomorphic and/or animated) characters, and it is unclear how children perceive such characters as sources of information. In this study, 92 3- to 5-year-olds saw images of characters and chose which would be best for learning about six topics across three domains: animal biology, human biology, and socioemotional. Children were randomized to one of three conditions in which they chose between paired images of (1) live-action humans versus animated humans (i.e., holding character type constant and varying format), (2) animated humans versus animated anthropomorphic animals (i.e., holding format constant and varying character type), or (3) live-action humans versus animated anthropomorphic animals (i.e., most realistic vs. least realistic character choices). Results indicated that children chose animated characters over live-action characters (Conditions 1 and 3). They did not choose humans significantly more often than animals even for human biology and socioemotional lessons (Conditions 2 and 3). However, in Condition 2, they chose animals significantly more often than humans for animal biology lessons. In sum, children showed little sign of prioritizing realism. The study adds children's perspectives to the literature on the effects of reality cues on early learning from educational TV.


Further identification of PGE1 metabolites formed in the cat lung.
Tritium-labeled compounds appearing in the venous effluent of isolated blood perfused cat lungs after infusion of [3H]prostaglandin E1 (PGE1) appear to be unchanged [3H]PGE1 and 13,14-dihydro-15-keto-PGE1. No 15-keto-PGE1 could be detected in the venous effluent.


Screening the effective components of Suanzaoren decoction on the treatment of chronic restraint stress induced anxiety-like mice by integrated chinmedomics and network pharmacology.
Suanzaoren decoction (SZRD) is a classical traditional Chinese prescription. It is widely used to treat mental disorders, including insomnia, anxiety, and depression, in China and other Asian countries. However, the effective components and mechanisms underlying SZRD remained unclear. We aimed to develop a new strategy to discover the effects and potential mechanisms of SZRD against anxiety and to further reveal the effective components of SZRD in treating anxiety. First, the chronic restraint stress (CRS)-induced mouse model of anxiety was orally administered SZRD, and behavioral indicators and biochemical parameters were applied to assess efficacy. A chinmedomics strategy based on UHPLC-Q-TOF-MS technology and network pharmacology were then used to screen and explore potentially effective components and therapeutic mechanisms. Finally, molecular docking was applied to further confirm the effective components of SZRD, and a multivariate network for anxiolytic effects was constructed. SZRD exerted anxiolytic effects by increasing the percentage of entries into open arms and the time spent in open arms; improving hippocampal 5-HT, GABA, and NE levels; and increasing serum corticosterone (CORT) and corticotropin-releasing hormone (CRH) levels caused by CRS challenge. Beside, SZRD exerted a sedative effect by decreasing sleep time and prolonging sleep latency with no muscle relaxation effect in CRS mice. A total of 110 components were identified in SZRD, 20 of which were absorbed in the blood. Twenty-one serum biomarkers involved in arachidonic acid, tryptophan, sphingolipid, and linoleic acid metabolism were identified after SZRD intervention. Finally, a multivariate network including prescription-effective components-targets-pathway of SZRD treating anxiety, including 11 effective components, 4 targets and 2 pathway was constructed. The current study demonstrated that integrating chinmedomics and network pharmacology was a powerful approach to investigating the effective components and therapeutic mechanisms of SZRD and provided a solid basis for the quality marker (Q-marker) of SZRD.


School-Based Autism Rates by State: An Analysis of Demographics, Political Leanings, and Differential Identification.
We reviewed federal special education data to determine school-identified prevalence of Autism Spectrum Disorder (ASD) and other disability categories by U.S. state. We also examined whether state-level policies, demographic factors, and rates of other eligibility categories are predictive of these state ASD rates. Results indicate that overall, 1 of 81 school-aged children are served under an ASD special education eligibility. State-level demographic factors, such as socioeconomic status and political leanings were highly predictive of rates of ASD. States with higher rates of ASD had lower rates of intellectual and learning disabilities, but higher rates of Other Health Impairment (OHI).


Cerebrospinal fluid kallikrein in spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.
To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats. The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states. Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography. In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats. The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.


Stalling by RNA polymerase II in the polyomavirus intergenic region is dependent on functional large T antigen.
RNA polymerase II encounters an elongation block and stalls in vivo during transcription of the late strand of polyomavirus DNA. In this study, we performed transcriptional run-on assays and localized the stalling site to a 164-nucleotide region (nt 11-175) that contains specific binding sites for polyomavirus large T antigen. The effect of large T antigen on elongation by RNA polymerase II through this region was examined in cells infected with a mutant polyomavirus (AT3-ts25E) which encodes a thermolabile large T antigen. Removal of functional large T antigen by shifting to the nonpermissive temperature (39 degrees) eliminated stalling by RNA polymerase in this region, although RNA polymerases transcribing other regions of the viral genome were unaffected. RNA polymerase resumed stalling when functional large T antigen was again allowed to accumulate by shifting back to the permissive temperature (32 degrees). We conclude that stalling by RNA polymerase II in vivo is dependent on the presence of functional large T antigen.


Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient.
A patient with Type 1 (insulin-dependent) diabetes mellitus developed localised amyloidosis at the sites of his injections of porcine insulin. A major amyloid fibril protein was extracted and, by means of its amino acid composition and amino acid sequence, it was shown to contain intact insulin molecules. Porcine insulin is the tenth protein and the first foreign protein to be chemically identified in human amyloid fibrils.


Occurrence of emerging contaminants in biosolids in northern Queensland, Australia.
This study aims to identify and quantify different classes of emerging contaminants (ECs), such as pharmaceutical and personal care products (PPCPs), per-and polyfluoroalkyl substances (PFAS), heavy metals (HMs), polycyclic musks (PMs) in biosolids from different sewage treatment plants (STPs) from regional councils across Northern Queensland, Australia. Biosolids samples were named BS1 to BS7 for each council. The results revealed significant variations in the concentrations of different ECs in biosolids which could be explained in some instances by the characteristics of the upstream sewage network. For instance, BS4-biosolids from a small agricultural shire (largely sugarcane) showed the highest concentration of zinc and copper, which were 2430 and 1050 mg/kg, respectively. Among PPCPs, the concentration of ciprofloxacin was found to be the highest in BS3 and BS5, two large regional council areas which are a mix of domestic and industrial (predominantly domestic) biosolids of 1010 and 1590 ng/g, respectively. In addition, the quantity of sertraline was consistently high in all biosolids except from BS7, one of the smaller regional councils, which is indicative of the domestic catchments attached. PFAS compounds were detected in all biosolids samples except in BS6, one of the small (agricultural and tourist) catchments. Two PFAS compounds emerged as the most common pollutants that were perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). The largest industrial catchment biosolids, BS2 showed the highest concentration of PFOS at 253 ng/g, while the smallest regional council, BS7 showed the maximum concentration of 7.90 ng/g of PFOA. Overall, this study concludes that certain ECs such as HMs, antibiotics, PFOS and PFOA in biosolids may pose high environmental risks.


Carcinogenesis in Fischer rats by nitrosodipropylamine, nitrosodibutylamine and nitrosobis(2-oxopropyl)amine given by gavage.
Nitrosodi-n-propylamine, nitrosodi-n-butylamine and the ketone nitrosobis(2-oxopropyl)amine were administered by gavage to F344 rats at doses of 1 and 2 mmol for 30 weeks. The higher level of nitrosodipropylamine led to death of all the animals with carcinomas of the liver, nasal cavity and esophagus by the 40th week. At the lower level the rats died of these tumors but survived to week 60. In contrast, 1 mmol of nitrosobis(2-oxopropyl)amine did not cause death of all the animals until week 95, and fewer than half of them had liver carcinomas; none had tumors of the esophagus or nasal cavity. Nitrosodi-n-butylamine was a much weaker carcinogen than nitrosodipropylamine, since 80% of the rats given 2 mmol survived until week 83. Although, with this compound, the lifespan of the rats was not greatly shortened, a large variety of tumors was induced; about 60% of the animals had liver carcinomas, 50% forestomach carcinomas and 35% transitional cell carcinomas of the urinary bladder.


Pattern of chest computerized tomography scan findings in symptomatic RT-PCR positive Covid-19 patients at the Korle Bu Teaching Hospital, Ghana.
Chest Computerized Tomography (CT) features of Corona Virus Disease 2019 (COVID-19) pneumonia are nonspecific, variable and sensitive in detecting early lung disease. Hence its usefulness in triaging in resource-limited regions. To assess the pattern of chest CT scan findings of symptomatic COVID-19 patients confirmed by a positive RT-PCR in Ghana. This study retrospectively reviewed chest CT images of 145 symptomatic RT-PCR positive COVID-19 patients examined at the Radiology Department of the Korle Bu Teaching Hospital (KBTH) from 8th April to 30th November 2020. Chi-Squared test was used to determine associations among variables. Statistical significance was specified at p≤0.05. Males represent 73(50.3%). The mean age was 54.15±18.09 years. The age range was 5 months-90 years. Consolidation 88(60.7%), ground glass opacities (GGO) 78(53.8%) and crazy paving 43(29.7%) were the most predominant features. These features were most frequent in the elderly (≥65years). Posterobasal, peripheral and multilobe disease were found bilaterally. The most common comorbidities were hypertension 72(49.7%) and diabetes mellitus 42(29.2%) which had significant association with lobar involvement above 50%. The most predominant Chest CT scan features of COVID-19 pneumonia were GGO, consolidation with air bronchograms, crazy paving, and bilateral multilobe lung disease in peripheral and posterior basal distribution.


Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3 cells: evidence for a role of a p38gamma-dependent signaling pathway.
A novel branch of the Ras family, Rit, was recently identified. Rit exhibits a distinct C-terminus and effector domain, and does not activate mitogen-activated protein kinase (MAPK) but can cooperate with Raf to transform fibroblasts. Here, we found that when overexpressed, activated mutants of Rit transform NIH 3T3 cells efficiently, and stimulate p38gamma but not MAPK, p38alpha, p38gamma, p38delta, or ERK5. Furthermore, we provide evidence that p38gamma activation is required for the ability of Rit to stimulate gene expression and cellular transformation. These findings suggest that this unique GTPase stimulates proliferative pathways distinct from those regulated by other Ras family members.


Heparin: 100 years of pleiotropic effects.
Heparin is a glycosaminoglycan with anticoagulant properties and antiinflammatory effects. The discovery of heparin approaches its 100th year and its antiinflammatory properties still draws much attention and anticipation to new possibilities of use and the likelihood of developing heparin-like drugs that lacked the anticoagulation effects. It is known that heparins limit the embolization and the extension of the thrombus, although they do not promote its complete lysis in most cases. The complexity and pleiotropic characteristics of these glycosaminoglycans still challenge science, to the point in which approaches hitherto unusual appear repeatedly in the literature. New indications, accompanied by longtime consecrated others, dismantle the idea of an outdated medication and create high expectations for the near future. The objective of this review is to analyze the pleiotropic effects of heparin and its use in several diseases, highlighting its safety and effectiveness.


Association of preterm birth with sustained postnatal inflammatory response.
To investigate fetal or neonatal inflammatory patterns based on 25 inflammatory markers in neonatal dried blood spots samples from infants born preterm and term, collected several days after birth. Dried blood spots samples from 160 neonates were analyzed for 25 inflammatory markers using multiplex technology: 26 neonates born very preterm (before 32 weeks of gestation), drawn at a mean 6 days (95% confidence interval [CI], 5-7 days) after birth; 52 born preterm (32-36 weeks of gestation), drawn at mean 5 days (95% CI, 5-6 days) after birth; and 82 born at term (at or after 37 weeks of gestation), drawn at mean 5 days (95% CI, 5-5 days) after birth. Markers statistically significantly associated with preterm birth were analyzed in a multivariable model together with maternal and neonatal risk factors for preterm birth. Elevated levels of interleukin (IL)-1beta, IL-6, soluble IL-6ralpha, IL-8, matrix metalloproteinase-9, and transforming growth factor-beta1 and decreased levels of IL-18, brain-derived neurotrophic factor, and C-reactive protein were associated with preterm birth. Maternal risk factors could explain only an increase of IL-1beta, whereas neonatal factors could explain several of the elevated and decreased inflammatory markers in the dried blood spots samples from the infants born preterm compared with the infants born at term. The differences in levels of inflammatory markers in dried blood spots samples from infants born preterm compared with infants born at term supports the hypothesis that inflammation of fetal origin might be a cause of preterm birth. II.


Ultrastructural detection of kinetochores by silver impregnation.
We describe a simple silver impregnation method for the ultrastructural detection of kinetochores on meiotic chromosomes of the grasshopper Eyprepocnemis plorans. Testes were fixed with glutaraldehyde and silver-impregnated. After Epon 812 embedding, ultrathin cutting and counterstaining with uranyl acetate, sections were studied by transmission electron microscopy. The meiotic chromosomes showed differentially silver-impregnated 'ball and cup' kinetochores. Some pericentriolar material also showed silver deposits. These observations are discussed in the light of previous results obtained by light microscopy of silver-stained spermatocytes in which both kinetochores and pericentriolar material were also preferentially stained. These results suggest a role for acidic proteins in the composition of these structures.


Pre- and post-stroke oral antithrombotics and mortality in patients with ischaemic stroke.
Reducing stroke occurrence requires the effective management of cardiovascular and other stroke risk factors. To describe pre- and post-stroke medication use, focusing on antithrombotic therapy and mortality risk, in individuals hospitalised for ischaemic stroke (IS) in the United Kingdom. Using primary care electronic health records from the United Kingdom, we identified patients hospitalised for IS (July 2016-September 2019) and classed them into three groups: atrial fibrillation (AF) diagnosed pre-stroke, AF diagnosed post-stroke, and non-AF stroke (no AF diagnosed pre-/post-stroke). We determined use of cardiovascular medications in the 90 days pre- and post-stroke and calculated mortality rates. There were 3201 hospitalised IS cases: 76.2% non-AF stroke, 15.7% AF pre-stroke, and 8.1% AF post-stroke. Oral anticoagulant (OAC) use increased between the pre- and post-stroke periods as follows: 54.3%-78.7% (AF pre-stroke group), 2.3%-84.8% (AF post-stroke group), and 3.4%-7.3% (non-AF stroke group). Corresponding increases in antiplatelet use were 30.8%-35.4% (AF pre-stroke group) 38.5%-47.5% (AF post-stroke group), and 37.5%-87.3% (non-AF stroke group). Among all IS cases, antihypertensive use increased from 66.8% pre-stroke to 78.8% post-stroke; statin use increased from 49.6%-85.2%. Mortality rates per 100 person-years (95% CI) were 17.30 (14.70-20.35) in the AF pre-stroke group and 9.65 (8.81-10.56) among all other stroke cases. Our findings identify areas for improvement in clinical practice, including optimising the level of OAC prescribing to patients with known AF, which could potentially help reduce the future burden of stroke.


Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study.
Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation. The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared. The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03-6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status. KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.


Inhomogeneous antibiotic distribution in sediment profiles in anthropogenically impacted lakes: Source apportionment, fate drivers, and risk assessment.
Antibiotic residues in lake ecosystems have been widely reported; however, the vertical distribution of antibiotics in lake sediment profiles have rarely been examined. This study systematically revealed the vertical distribution pattern, sources, and risks of antibiotics in sediments of four typical agricultural lakes in central China. Nine of 33 target antibiotics were detected with a total concentration range of 39.3-18,250.6 ng/g (dry weight), and the order of average concentration was erythromycin (1447.4 ng/g) > sulfamethoxazole (443.7 ng/g) > oxytetracycline (62.6 ng/g) > enrofloxacin (40.7 ng/g) > others (0.1-2.1 ng/g). The middle-layer sediments (9-27 cm) had significantly higher antibiotic detected number and concentration than those in the top layer (0-9 cm) and bottom layer (27-45 cm) (p < 0.05). Correlation analysis showed that significant relationships existed between antibiotic concentrations and the octanol-water partition coefficients (Kow) of antibiotics (p < 0.05). Redundancy analysis indicated that Pb, Co, Ni, water content, and organic matter (p < 0.05) jointly affected the distribution of antibiotics in sediment profiles. Risk assessment showed that the highest potential ecological and resistance selection risks of antibiotics occurred in the middle-layer sediments, and oxytetracycline, tetracycline, and enrofloxacin had the most extensive potential risks in the sediment profiles. Additionally, the positive matrix factorization model revealed that human medical wastewater (54.5%) contributed more antibiotic pollution than animal excreta (45.5%) in sediment. This work highlights the inhomogeneous distribution of antibiotics in sediment profiles and provides valuable information for the prevention and control of antibiotic contamination in lakes.


Inhibiting effects on the induction of cytotoxic T lymphocytes by dendritic cells pulsed with lysates from acute myeloid leukemia blasts.
Dendritic cells (DCs) were established from 25 patients in complete remission of acute myeloid leukemia (AML). In patients during hematopoietic regeneration following chemotherapy the yield of DC was comparable to that of healthy donors. In patients, more than 2 months after chemotherapy, significantly less DC were generated. Comparison of the antigen-presenting capacity using tetanus toxoid of six AML patients and six healthy volunteers did not show significant differences. In six AML patients, lymphocytes stimulated with blast cell lysate pulsed DC were analyzed for cytotoxic activity against autologous blast cells. 8.4-35.6% of autologous blast cells were lysed by DC stimulated lymphocytes. In three of the six patients maximum lysis of target cells was achieved by unpulsed DC. Thus, it seems that in some patients blast cell lysates mediate inhibitory effects, which may explain to some extend immune escape mechanisms in AML.


Exogenous and endogenous stages of Eimeria perforans naturally infected domestic rabbit (Oryctolagus cuniculus) in Saudi Arabia: Light microscopic study.
Exogenous and endogenous stages of Eimeria perforans naturally infected rabbits in Saudi Arabia were described. The prevalence of infection was 75%. Oocysts were ovoid to elliptical and measured 16 × 10 μm. The four dizoic sporocysts were ovoid and measured 7 × 5 μm. Endogenous stages were restricted to the duodenum. Meronts, microgamonts, macrogamonts and young oocysts were recorded and described.


Effect of 1 Hz repetitive transcranial magnetic stimulation over the auditory cortex on audiometry and otoacustic emissions.
Repetitive transcranial magnetic stimulation (rTMS) at low frequencies (≤1 Hz) delivered to the primary motor cortex for 15 min or longer has been shown to reduce motor cortex excitability. Over the visual cortex, 1 Hz rTMS led to increased phosphene thresholds and over the auditory cortex rTMS reduced auditory evoked potentials. rTMS above the auditory or temporo-parietal cortex has also been reported to reduce the severity of auditory hallucinations and the perception of tinnitus. However, possible unwanted effects on hearing function have not yet been investigated systematically. 12 right-handed normal hearing subjects (5 male, mean age 28.2 ± 4.3) received a single session of 18 min 1 Hz rTMS at 90% resting motor threshold intensity using an established coil positioning method targeting the Heschl's area of the left superior temporal gyrus. Standard pure tone audiometry and distortion-products otoacustic emissions (DPOAE) were performed before and immediately after stimulation. The main finding was that one session of 1 Hz rTMS over the temporal cortex modified neither the auditory threshold meaningfully nor the presence of DPOAE in healthy subjects. In conclusion, we found in this pilot approach no obvious indication for auditory dysfunctions due to direct electromagnetic stimulation of the superior temporal gyrus after one session of rTMS in healthy controls that may be interpreted as unwanted side effects. Nevertheless monitoring of auditory functions is strongly recommended in future clinical trials stimulating the auditory cortex, as this has not been done systematically in the past.


Ovarian torsion associated with appendicitis in a 5-year-old girl: a case report and review of the literature.
Acute ovarian torsion is an uncommon cause of abdominal pain in female children and is often difficult to differentiate from other conditions causing lower abdominal pain. Acute adnexal pathology associated with appendicitis is very rare, with only a handful of reports available in the literature. Reported is a case of ovarian torsion associated with appendicitis in a 5-year-old girl along with a comprehensive literature review.


Sarcoidosis associated pleural effusion: Clinical aspects.
A sarcoidosis associated pleural effusion (SAPE) is a pleural effusion caused by active granulomatous inflammation from sarcoidosis. We describe the epidemiology, clinical features, diagnostic approach, treatment strategies and outcome of this condition. SAPE occurs in approximately 1% of sarcoidosis patients. The condition most commonly occurs at the initial presentation of sarcoidosis or within the first year. Dyspnea is the most common presenting symptom. Although a definitive diagnosis of SAPE requires a pleural biopsy, the diagnosis may be established on the basis of clinical features alone provided that alternative conditions can be reliably excluded. Pleural fluid analysis is essential in establishing the clinical diagnosis of SAPE. Corticosteroids are the drugs of choice for SAPE, and they are usually rapidly effective with courses of therapy often lasting less than two months. SAPE tends to have a low rate of recurrence that appears be to lower than for many other forms of sarcoidosis.


The Role of Ipsilateral Tonsillectomy in the Extirpation of Branchial Cleft Anomalies- A Retrospective Monocentric Analysis Over 13 Years.
Branchial cleft anomalies (BCA) can occur as sinuses, fistulas or cysts. They arise from the first, second, third or fourth pharyngeal cleft due to non-fusion or subinvolution. Mostly, located in Robbin's neck-level II, BCA clinically present as a painless compressible swelling, cutaneous draining sinus, or fistula. Surgical treatment is the gold standard to prevent recurrence in BCA, though the necessity of ipsilateral tonsillectomy is discussed and was being examined within this work. In retrospect, data was collected from patients, that were admitted with the diagnosis BCA between 2006 and 2020 in an academic tertiary care center. 160 patients met inclusion criteria, the data was further evaluated, the focus was set on the occurrence of recurrence. Recurrence of BCA was observed in 2 out of 160 surgically treated patients (1,25%), one of them with simultaneous tonsillectomy, the other without. A statistically significant difference in the recurrence-rate between these two groups (with/without tonsillectomy) could not be shown. The performance of an ipsilateral simultaneous tonsillectomy in the surgical workup of BCA cannot be recommended at the basis of our data. The online version contains supplementary material available at 10.1007/s12070-023-03543-5.


Biotransformation of 14-deoxy-14-methylenetriptolide into a novel hydroxylation product by Neurospora crassa.
The biotransformation of 14-deoxy-14-methylenetriptolide by Neurospora crassa CGMCC AS 3.1604 to produce a new hydroxylation derivative was studied. The structure of this novel compound was determined using spectral data. This biotransformation using whole cells conditioned for 4 days transformed approximately 65% (mol ratio) of the substrate into the compound (5R)-5-hydroxy-14-deoxy-14-methylenetriptolide.


The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial.
We investigated the effects of celecoxib, diclofenac, and ibuprofen on the disease-specific quality of life, synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis (OA). Ninety patients scheduled for a total knee arthroplasty (TKA) were randomized to six groups that were treated with low and high dosages of celecoxib, diclofenac or ibuprofen. At the time of the first admission (T0) and at surgery (T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs (NSAIDs)), samples of knee synovial fluid were obtained from each patient for analysis. During the surgery the synovial tissue was harvested from the knee of patients. The Western Ontario and McMaster universities (WOMAC) score was used to evaluate the patient disease-specific quality of life at T0 and T1. Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)-alpha, Interleukin-6 (IL-6), IL8 and Vascular endothelial growth factor (VEGF) concentration in the synovial fluid. Western blot assays evaluated the effects of NSAIDs on MAP kinase (MAPK) signal transduction pathway in the synovial membrane. NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6, VEGF and TNF-alpha concentration in the synovial fluid. Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid. Inhibition of MAPKs was noted after NSAID treatment. Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA. Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs. ClinicalTrial.gov: NCT01860833.


Swimming and the heart.
Exercise training is accepted to be beneficial in lowering morbidity and mortality in patients with cardiac disease. Swimming is a popular recreational activity, gaining recognition as an effective option in maintaining and improving cardiovascular fitness. Swimming is a unique form of exercise, differing from land-based exercises such as running in many aspects including medium, position, breathing pattern, and the muscle groups used. Water immersion places compressive forces on the body with resulting physiologic effects. We reviewed the physiologic effects and cardiovascular responses to swimming, the cardiac adaptations to swim training, swimming as a cardiac disease risk factor modifier, and the effects of swimming in those with cardiac disease conditions such as coronary artery disease, congestive heart failure and the long-QT syndrome.


Clinical outcomes following stent implantation in internal mammary artery grafts.
We evaluated our experience with percutaneous coronary intervention (PCI) of internal mammary artery (IMA) grafts. From the institution's database we identified 288 patients with 311 IMA lesions. Of these, 82 (26.4%) had stents placed during PCI. Angiographic success was 92%. Mortality at 1 month was 1.7%, myocardial infarction (MI) 15.7%, and target lesion revascularization (TLR) 0.4%. Cumulative 1-year event rates were mortality 6.4%, MI 20.4%, and TLR 8.0%. TLR rates were significantly higher in the stented lesions than lesions treated with angioplasty alone (19.2% vs. 4.9%; P = 0.004). The higher TLR rate in stented lesions was most apparent at the anastomotic site (25.0% vs. 4.2%; P = 0.006). Percutaneous revascularization of IMA grafts can be performed safely with high procedural success and excellent short- and long-term results. Stenting, particularly at the anastomotic site, was associated with significantly greater rates of TLR than angioplasty alone.


Evaluation of the negative cooperativity model for fat cell beta-adrenergic receptors.
Cooperative site-to-site interactions among beta-adrenergic receptors of fat cell membranes are probed with the potent beta-adrenergic antagonist (-)-[3H]dihydroalprenolol according to the kinetic method of De Meyts et al. (De Meyts, P., Roth, J., Neville, Jr., D.M., Gavin, III, J.R., and Lesniak, M.A. (1973) Biochem. Biophys. Res. Commun. 55, 154--161). Dissociation of specific (-)-[3H]dihydroalprenolol binding from fat cell membranes following a 100-fold dilution was rapid at 37 degrees C; only 40% of the initial equilibrium binding remained 30 s after dilution. Dissociation of (-)-[3H]dihydroalprenolol bound under conditions yielding approximately 20% initial occupancy was performed in the absence and in the presence of a large molar excess of beta-adrenergic agonist ((-)-isoproterenol) or beta-adrenergic antagonist ((-)-alprenolol or (-)-propanalol). Neither agonists nor antagonists influenced the rate of (-)-[3H]dihydroalprenolol dissociation from fat cell membranes performed at 4, 22 or 37 degrees C. Although analysis of the steady-state binding of (-)-[3H]dihydroalprenolol to fat cell membranes yields Hill coefficients, nH, less than 1.0, the present study indicates that these fat cell beta-adrenergic receptors display no cooperative site-to-site interactions.


Peptide histidine isoleucine (PHI) immunoreactivity in the rat retina: identification and characterisation by radioimmunoassay, immunohistochemistry and high-performance liquid chromatography.
The presence of peptide histidine isoleucine immunoreactivity (PHI-IR) in the retinae of male Wistar rats has been demonstrated using a specific radioimmunoassay (RIA), immunohistochemistry (IHC) and high performance liquid chromatography (HPLC). PHI levels (mean +/- S.E.M.) of 16.68 +/- 1.61 ng/g wet weight of normal retinal tissue were measured by RIA. IHC showed PHI-IR to be localized to a population of amacrine cells distributed along the proximal aspect of the inner nuclear layer and to processes in laminae I and IV of the inner plexiform layer. PHI-IR in retinal extracts was shown to coelute with a synthetic porcine PHI standard on a reverse phase HPLC system. Additionally levels of PHI-IR were significantly increased (P less than 0.001) with light adaptation.


Pathological observations on experimental cytomegalovirus infections in pregnancy.
Cytomegalovirus injected intramuscularly or intraperitoneally into mice on the 8th day of pregnancy resulted in a significant retardation in foetal growth and a reduced number of offspring surviving until near-term. Pathological changes consisted of inflammatory cell infiltration in the liver, heart, salivary glands and adrenal cortex of affected animals. Necrotic changes were also present in the adrenal cortex in most severely affected animals following intraperitoneal injection of virus. Intraperitoneal infection led to a frank peritonitis and marked splenic necrosis with a degeneration and inflammation of visceral fatty tissue and lymphadenitis. In contrast, intramuscular injection of virus did not produce a peritonitis but the spleen was greatly enlarged with reaction centres and increased numbers of lymphocytes being identified at histology. As a consequence of cytomegalovirus infection in pregnant mice foetal growth impairment and intrauterine death was seen. This was related to the severity of pathological changes in the mothers. In those animals dying or appearing sick at near-term, most foetuses were dead and resorbing. Since murine cytomegalovirus was not identified by inclusion body formation in foetal or placental tissues in this study and virus has not been isolated from these tissues previously, it was concluded that the mechanism for the impaired foetal growth was of an indirect nature and attributable primarily to a severe generalised maternal illness.


Intermittent interatrial block after electrical cardioversion for atrial fibrillation.
A 67-year-old woman with persistent atrial fibrillation presented for elective electrical cardioversion. The patient was cardioverted to normal sinus rhythm with a synchronized 150 joules (J) biphasic shock. Varying P-wave morphology suggesting intermittent interatrial block (IAB) was noted after the cardioversion on the rhythm strip. Three minutes later the patient developed early recurrence of atrial fibrillation and a second successful 150 J biphasic shock was delivered; IAB was still evident on a single lead II monitoring. However, the patient remained in sinus rhythm. The patient was discharged in normal sinus rhythm with electrocardiographic evidence of intermittent interatrial block. This case report examines the occurrence of IAB postcardioversion for atrial fibrillation and speculates on its prognostic significance.


Structure of the O56 antigen of Escherichia coli, a polysaccharide containing 7-substituted alpha-N-acetylneuraminic acid.
The O56 polysaccharide moiety of the O56 antigen (LPS) consists of D-glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, and N-acetylneuraminic acid in the molar ratios 1:1:1:1. Methylation analysis, periodate oxidation, mild acid hydrolysis, as well as 1H and 13C NMR spectroscopy showed that the O56 polysaccharide has the primary structure [formula: see text]


Chemokine expression by central nervous system resident cells and infiltrating neutrophils during experimental autoimmune encephalomyelitis in the BALB/c mouse.
The active role of chemokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. In this study the expression pattern of several chemokines and cytokines was elucidated using reverse transcription-PCR and immunohistochemistry in a recently established EAE model of the BALB/c mouse that is characterized by CNS infiltration of polymorphonuclear neutrophils. Elevated mRNA levels of the chemokines MIP-1alpha, MIP-2 and MCP-1 were detected in the CNS of diseased mice, whereas no chemokine expression could be measured in asymptomatic mice. Activated astrocytes were shown to be the main source of MIP-1alpha and MIP-2 before and during cellular CNS infiltration. Among the infiltrating immune cells the neutrophils secreted MIP-1alpha and MCP-1. These results suggest involvement of ordered chemokine expression during the process of neutrophil attraction into the CNS, which may play an important role in the initiation and perpetuation of autoimmune CNS inflammation in the BALB/c mouse. This is the first EAE model to describe CNS expression of the C-X-C chemokine MIP-2, corresponding to an observed neutrophil accumulation in the CNS.


Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners.
Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients.


Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.
Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)


Response of peripheral collateral arteries in the dog to prostaglandins E1, E2, F2 alpha, and I2 (prostacyclin).
Prostaglandins (PG) E2, E2, E2 alpha, and I2 [prostacyclin (PGI2)] were tested in vitro on collateral arteries that enlarge following chronic occlusion of the femoral artery in the dog. After contraction with an ED50 dose of KCl, serial doses of a PG were added. Collateral arteries relaxed significantly to PGI2 (10(-7)--10(-5) M). Normal, similarly sized branch arteries did not relax. The contractile response of collateral arteries to PGE1, PGE2, and PGF2 alpha was qualitatively similar to that of branch arteries, but the magnitude of the responses for collateral arteries was PGF2 alpha = PGE2 greater than PGE1. The magnitude of the response for branch arteries was PGF2 alpha much greater than PGE2 greater than PGE1. The effects of the PGs on anterior tibial arteries from the contralateral limb and on anterior tibial arteries exposed to low pressure below the occlusion did not differ. Thus the lowered pressure in the limb with the occluded femoral artery was not responsible for differences in the effects of the PGs on collateral arteries. Collateral arteries are more sensitive to the relaxant effects of PGI2 in high doses and are less sensitive to the contractile effects of other PGs, particularly PGF2 alpha, than similarly sized arteries. This suggests that therapeutic doses of PGI2 may increase blood flow to ischemic areas.


Prehospital trauma system in a low-income country: system maturation and adaptation during 8 years.
Of all deaths from injury, 90% occur in low- and middle-income countries, and most of the injured die before reaching a hospital. We have previously shown that a rural trauma system in Northern Iraq significantly reduced mortality in victims of mines and war injuries. In this follow-up study, we evaluated the adaptation and maturation of the system to changing injury patterns, focusing on mortality, time intervals from injury to medical help, and treatment effect on the physiologic impact of injuries. Approximately 6,000 first responders and 88 paramedics were trained in Northern Iraq from 1996 to 2004 and treated 2,349 victims. All patients were prospectively registered with monitoring of time intervals, interventions performed, prehospital treatment effect, and mortality. Injury pattern changed markedly during the study period, with penetrating injuries decreasing from 91% to 15%. Mortality in victims of mines and war injuries (n = 919) decreased from 28.7% to 9.4% (p = 0.001), as did the time interval from injury to first medical help, from 2.4 hours to 0.6 hours (p = 0.002). The prehospital treatment effect improved significantly in the later part of the study period compared with the first years (p < 0.0005). Improvement was maintained in new injury groups. Retention of paramedics in the program was 72% after 8 years. This low-tech prehospital emergency system designed for dealing with penetrating trauma matured by reducing time to first medical help and by improving physiologic parameters after prehospital treatment during the 8-year study period. The program adapted to changing injury patterns without compromising results.


Clinical feasibility of a novel biphasic osteochondral composite for matrix-associated autologous chondrocyte implantation.
Matrix-associated autologous chondrocyte implantation has been used to treat cartilage defects. We developed a biphasic cylindrical osteochondral composite construct for such use, and conducted this study to determine its feasibility for treating osteochondral lesions in human knees. Ten patients with symptomatic osteochondral lesions at femoral condyles were treated by replacing pathological tissue with the construct of dl-poly-lactide-co-glycolide, whose lower body was impregnated with β-tricalcium phosphate and served as osseous phase. The construct had a chamber to load double-minced autologous cartilage, serving as source of chondrocytes. Osteochondral lesion was drill-fashioned a pit of identical dimension as the construct. Chondrocyte-laden construct was press-fit to fill the pit. Postoperative outcome was evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS) scale up to 24 months. Magnetic resonance image was taken, and sample tissue was collected with second-look arthroscopic needle biopsy at 12 months. Outcome parameters were primarily safety of surgery, and secondarily postoperative change in KOOS and regeneration of hyaline cartilage and cancellous bone. No patient experienced serious adverse events. Postoperative mean KOOS in "symptoms" subscale had not changed significantly from pre-operation until 24 months; whereas those in the other four subscales were significantly higher than pre-operation at 12 and 24 months. Second-look arthroscopy showed completely filled grafted sites, with regenerate cartilaginous surfaces flushed with surrounding native joint surface. Microscopically, regenerated cartilage appeared hyaline. This novel construct for chondrocyte implantation is safe for surgical application in knee. It repairs osteochondral lesions of femoral condyles by successful regeneration of hyaline cartilage.


Receptor for activated C kinase (RACK) and protein kinase C (PKC) in egg activation.
In somatic cells, translocation of PKCs is facilitated by receptor for activated C kinase (RACK); however its involvement in egg activation is still elusive. We have followed the translocation pattern of conventional and novel PKCs (cPKCs and nPKCs, respectively) upon egg activation. Confocal microscopy indicated the expression and localization of RACK1, a specific receptor protein for cPKCs. Activation of MII eggs, led to translocation to the egg cortex of PKCα, βII and δ and the co-translocation of RACK1, with both PKCα and PKCβII. The association of PKC and actin, both known to be involved in cortical granules exocytosis (CGE) with RACK1, was demonstrated by co-immunoprecipitation. Egg activation resulted in an increased RACK1 level along with a decreased level of PKCβII. Based on these results, we suggest that upon egg activation, RACK1 shuttles activated cPKCs to the egg cortex, thus facilitating CGE.


Socioeconomic disparities in outdoor branded advertising in San Francisco and Oakland, California.
Advertising exerts a powerful influence over consumer decision-making, and disproportionate marketing for unhealthy products may contribute to health inequities. The objective of this study was to examine socioeconomic and racial and ethnic disparities in outdoor branded advertising for products harmful to health in San Francisco and Oakland, CA. We collected cross-sectional data on outdoor advertising from 372 blocks with ≥ 1 residential or mixed-residential parcel in SF and Oakland in 2018-2019. Blocks were randomly sampled by city, land use, majority vs. non-majority Black and/or Hispanic composition, and upper and lower tertiles of household income. Advertisements were coded by product, healthfulness, and branding. Exposure variables were neighborhood household median income and percent of residents who were Hispanic of any race, non-Hispanic Asian, non-Hispanic Black, and non-Hispanic White. The primary outcome variable was block-level dichotomous presence of any unhealthy branded advertisement for food, beverage, alcohol, or tobacco. Analyses were unadjusted and adjusted for land use and number of total advertisements on each block. Each additional $10,000 in neighborhood household median income was associated with an 11% lower adjusted odds of having any unhealthy branded advertisements on the block (95%CI: 0.80-0.99; P = 0.03). There were no significant associations between neighborhood racial and ethnic composition and presence of unhealthy branded advertisements, but with each 10% higher neighborhood composition of Hispanic residents, there was a borderline significant higher presence of unhealthy branded advertisements (OR = 1.23; 95%CI: 1.00-1.51; P = 0.05). Results indicate that low-income neighborhoods were disproportionately exposed to outdoor branded advertisements for unhealthy products.


Formation of protein complexes in crowded environments--from in vitro to in vivo.
Traditionally, biochemical studies are performed in dilute homogenous solutions, which are very different from the dense mixture of molecules found in cells. Thus, the physiological relevance of these studies is in question. This recognition motivated scientists to formulate the effect of crowded solutions in general, and excluded volume in particular, on biochemical processes. Using polymers or proteins as crowders, it was shown that while crowding tends to significantly enhance the formation of complexes containing many subunits, dimerizations are only mildly affected. Computer simulations, together with experimental evidence, indicate soft interactions and diffusion as critical factors that operate in a concerted manner with excluded volume to modulate protein binding. Yet, these approaches do not truly mimic the cellular environment. In vivo studies may overcome this shortfall. The few studies conducted thus far suggest that in cells, binding and folding occur at rates close to those determined in dilute solutions. Obtaining quantitative biochemical information on reactions inside living cells is currently a main challenge of the field, as the complexity of the intracellular milieu was what motivated crowding research to begin with.


Pharmaceutical excipients. Adverse effects associated with inactive ingredients in drug products (Part I).
Excipient reactions have resulted from the use of clearly toxic substances (e.g. diethyleneglycol), the use of certain excipients in a susceptible group (e.g. very low birthweight neonates, patients with large surface area burns, patients with a history of asthma or contact dermatitis), the alteration of an excipient mixture resulting in altered bioavailability (e.g. phenytoin), and the deliberate or inadvertent extradural administration of preserved medications intended for intravenous use. Inadvertent excipient overdose has also occurred when unusually large doses of a drug containing a preservative were used [chlorbutol in morphine, ethanol in glyceryl trinitrate (nitroglycerin)]. Most excipient problems are preventable with knowledge of the currently available formulation. Government drug regulatory agencies have largely prevented introduction of a new toxic excipient; however, the new use of previously approved (but not adequately studied) excipients continues to result in unfortunate tragedies (e.g. the E-ferol incident). Populations at risk should be monitored carefully. Very low birthweight infants (less than 100g) have a well-demonstrated intolerance to many excipients, particularly during the first 2 weeks of life. Research should be directed toward development of non-preserved medications and safer diluents for this population. Drugs and excipients which have previously been demonstrated to be safer in other populations (e.g. doxapram) should be meticulously studied in this age group before widespread use is recommended. Asthmatic patients comprise another population that are frequently sensitive to excipient toxicity. In some cases, as in sulphiting agents, which are ubiquitous in foods as well as in medications, total avoidance may not be possible and prophylactic therapy may be beneficial. Inactive ingredients are clearly not consistently inert in their biological activity and therefore should not be listed as such. A more useful and concise term is excipient. It is highly recommended that all pharmaceutical manufacturers list all their excipients and make this available to practitioners and drug information centres. Alternatively or additionally, the package insert should list these excipients in accordance with good manufacturing procedures. This disclosure will help to determine the relative frequency and magnitude of problems (bioequivalence, toxicity, etc.) that excipients may have in the population, as well as enabling susceptible patients to avoid inadvertent exposure.


Intricate isavuconazole therapy of a subcutaneous nodule caused by Alternaria infectoria in a heart transplant recipient.
Invasive fungal infections have appeared to be increasingly emergent in immunocompromised patients, especially in solid organ transplant (SOT) recipients. The Alternaria genus encompasses more than 80 dematiaceus species. Among them, Alternaria alternata and Alternaria infectoria are the most frequent isolated as responsible for infection in humans. To our knowledge, we report the first case of a heart transplant recipient suffering from subcutaneous nodule caused by Alternaria infectoria and who was treated with isavuconazole. Despite all the promises of this new azole drug, one should keep in mind the potential great variability of the inter-individual responses for such complex patients. We demonstrate herein how it can be challenging to manage Alternaria infection in SOT recipients. More comprehensive studies and recommendations are expected in the context of Alternaria infections.


The evolution of professional identity: the case of osteopathic medicine.
The osteopathic medical profession was founded in the late 19th century and has become an accepted part of the medical establishment in the United States. Throughout its history, the osteopathic medical profession has attempted to define itself in a way that differentiates osteopathy from other alternative therapies and situates the profession as responsive to the changing health care needs of the American public. This article examines identity within the osteopathic profession by examining the ways in which the profession has created, maintained, and changed its identity in its over century-long existence. The case analysis presented here involves the examination of identity statements culled from several osteopathic data sources. The identity statements represent four specific time periods within the osteopathic profession: the founding statements of A. T. Still, statements from 1915 through 1935 when the scope of osteopathic identity was expanding, statements from 1954 through 1974 in which the osteopathic profession dealt with internal and external threats in developing a "separate but equal" identity, and recent statements from a osteopathic student web site that illustrate current and future views of osteopathic identity. The results of this case analysis highlight the role of the social environment in establishing and changing professional identity, the importance of an occupational founder in shaping the articulation of identity, and the tension between identity and practice within the osteopathic medical profession.


Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004.
The World Health Organization (WHO) is undertaking consultations on immunological responses as parameters for evaluation and licensure of new Japanese encephalitis (JE) vaccines. Immunological markers could be used by vaccine developers and regulatory authorities to assess vaccine efficacy in absence of clinical efficacy data. The consultation which is reported here reviewed current data on mechanisms of protective immunity gathered from animal experimentation, clinical data from licensed vaccines and from vaccine candidates still in clinical development. Immunological assays and readouts for use in evaluation of candidate vaccines were also discussed. The consultation made a series of recommendations for specifications on immunological criteria to assess JE vaccine efficacy. More detailed recommendations will be drafted following further consultations to serve as WHO guidelines for evaluation and licensure for new JE vaccines.


Why are hospital-based nursing homes so costly? Relative importance of acuity and treatment setting.
To determine the extent to which higher costs in hospital-based skilled nursing facilities (HBSNF) can be explained by observable resident characteristics and unobservable selection effects, implying a design shortcoming of the skilled nursing facility prospective payment system (SNF PPS) implemented for Medicare-covered stays by the Balanced Budget Act of 1997 (BBA 1997). Data on resident characteristics from the Minimum Data Set (MDS) are combined with staff time costs from the Centers for Medicare and Medicaid Services' (CMS, formerly HCFA) 1995 and 1997 SNF Staff Time Measurement (STM) studies and nontherapy ancillary claim costs extracted from CMS SNF claim records. An endogenous switching model was estimated to measure the effect on costs of the relatively high acuity of HBSNF residents, net of differences purely attributable to the treatment setting. It was found that virtually the entire HBSNF differential is attributable to setting effects with resident characteristics and selection effects playing a negligible role. In addition, it was found that marginal costs associated with particular services and conditions are often lower in hospital-based than in freestanding facilities. HBSNFs incur high costs regardless of the characteristics of their residents. Their high fixed costs accompany relatively low marginal costs associated with admitting high-acuity residents. Consequently, a PPS casemix system that depends on resident characteristics and excludes consideration of facility characteristics (as mandated by BBA 1997) need not unfairly penalize HBSNFs, provided a powerful casemix system is used and HBSNFs specialize in the care of high-acuity residents.


Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.
Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.


Dissemination of doctor of nursing practice project findings: Benefits and challenges associated with publishing in healthcare journals.
Doctor of Nursing Practice (DNP) programs require a project to improve outcomes in a health care setting. However, dissemination methods vary. This evaluation examined benefits and challenges associated with submitting project manuscripts to a peer-reviewed health care journal in a DNP program with this requirement. Benefits and challenges were assessed with surveys completed by 85 DNP program alumni and 28 DNP mentors and by interviewing 5 faculty who teach in the DNP program and 5 editors of nursing journals. Benefits of completing a manuscript included sharing knowledge to improve health care outcomes and enhancing nursing scholarship. Among alumni, 81% reported manuscript development was beneficial and 69% published their work. Most students, most faculty, and all editors endorsed the requirement with alternatives for projects lacking rigor or innovation. Challenges included need for faculty involvement and editorial/statistical resources. Despite challenges, there are benefits of publishing rigorous and innovative DNP work.


Pharmacokinetic equivalence of 5(ethyl(2H)5)- and unlabelled phenobarbitone.
The present study shows the absence of in vivo pharmacokinetic isotope effect on phenobarbitone (PB) C5-ethyl deuteration (PBd5) following oral administration to man of equimolar PB/PBd5 mixtures (0.40 mmol each). Plasma PB and PBd5 (17 days) and urine PB, PBd5 and parahydroxy-metabolites (PBOH, PBHOd5) levels were determined by GC-MS. Isotope effect research includes comparison of pharmacokinetic parameters, study of time-dependence of isotope ratios (IRs) in plasma and urine (linearity test), comparison of IRs between samples and administered mixtures (Mann Whitney's test) and comparison of PBOH/PBOHd5 ratios before and after urine enzymatic hydrolysis (Student's two tailed t-test). No significant isotope effect was observed on pharmacokinetic parameters, PB hydroxylation or PBOH conjugation (x less than or equal to 5%); which the absence of pentadeuteration-induced alteration in PB's HSA binding parameters (binding mode, Ka, N) corroborates (x less than or equal to 5%). These results establish bioequivalence of PB and PBd5; the latter can be used with benefit in stable-isotope clinical pharmacology (steady state pharmacokinetics, drug interactions...) investigations as well as bioavailability studies of PB preparations.


Microeukaryote diversity in a marine methanol-fed fluidized denitrification system.
The marine methanol-fed fluidized denitrification system operated by the Montreal Biodome includes carriers on which a denitrifying biofilm has developed. Previous observations showed a high abundance of microeukaryotes living in and around the biofilm. These eukaryotes may influence the system's denitrification efficiency. The composition of the microeukaryote population was determined. Microscopic observations showed at least 20 different morphologies that included large numbers of ciliates. Molecular analyses of an 18S ribosomal RNA (rDNA) gene library revealed 31 different phylotypes. Alveolobiontes were the most abundant phylotypes and made up 75% of the 159 screened clones. Other eukaryotic groups, including Stramenopiles, Fungi, Amoebozoa, and nematodes, were also present. From 18S rDNA specific sequences, one of the Amoebozoa-affiliated phylotypes was visualized by fluorescence in situ hybridization. It had a rod-like irregular shape and measured less than 5 mum in length. We determined the impact of protozoans on the denitrifying activity. In a laboratory-scale batch culture assays, the denitrifying biofilm was treated with cycloheximide and nystatin that eliminated the protozoans. No difference in the denitrification rate was found. However, planktonic bacteria were more abundant in the treated culture medium.


Transplantation of bovine odontogenic tissues and dissociated odontogenic cells to hypothymic mice.
It was demonstrated in this study that bovine odontogenic tissues and the dissociated cell preparations of such tissues, when transplated to the subcapsular kidney site of hypothymic mice, retained their phenotypic expression and continued function to produce their recognisable products, dentine and enamel matrices. It was also shown that in the grafts of dissociated odontogenic tissues, cell sorting occurred so that histotypical tissues were formed and that their function produced readily recognisable dentine and enamel matrices. Attention has been drawn to the usefulness of this model for studying a variety of events that occur during odontogenesis.


Gastric ulcers differ from duodenal ulcers. Evaluation of basal acid output.
Patients with pyloric channel and prepyloric gastric ulcers are often considered to have an ulcer diathesis similar to patients with duodenal ulcers, while patients with more proximal gastric ulcers (ie, fundus, body, antrum) are excluded. To evaluate possible differences in basal acid outputs with regard to gastric ulcer location, basal acid outputs were determined by nasogastric suction in 80 patients with endoscopically documented benign active gastric ulcers. The results were compared to 65 normal subjects and 155 patients with endoscopically documented duodenal ulcers. There were no significant differences in basal acid outputs among the 80 patients with gastric ulcers with regard to location (ie, fundus-body, antrum, prepyloric, channel), and no significant differences compared to the 65 normal subjects. However, basal acid output for the 155 patients with duodenal ulcers was significantly different from the 80 patients with gastric ulcers (P < 0.05) and the 65 normal subjects (P < 0.05). Basal acid outputs tended to be higher and there was more gastric acid hypersecretion when gastric ulcers were located near the pylorus. However, irrespective of gastric ulcer location, basal acid outputs were higher in patients with duodenal ulcers. Seventy-one of the 80 patients with gastric ulcers were treated for eight weeks with standard doses of antisecretory medications, and endoscopic healing or nonhealing was documented. In 60 patients their gastric ulcers completely healed, while 11 patients had nonhealed gastric ulcers. There were no significant differences between the two groups with regard to gender, mean age, or basal acid output.(ABSTRACT TRUNCATED AT 250 WORDS)


Correction to: Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study.
The second author's name was incorrectly published as "Niha F. Younes". The correct name is "Nihal Farid Younes" as shown above in the list of authors.


Public domain computer-aided surgery (CAS) in orthodontic and maxillofacial surgery.
Computer-aided virtual three-dimensional (3D) surgical simulation assists the necessary visual understanding of complex pathological situations but has so far been dependent on expensive hardware and software. For the first time a non-commercial, user-orientated application for orthognathic and craniofacial surgical simulation has been introduced, based on freeware NIH Image 1.62 provided by the National Institute of Mental Health (NIMH). Use and limitations are demonstrated here by the example of hypertelorism surgery. The osteotomy lines and the amount of resection for outward positioning of the orbits were determined by the surgeon on a workstation using CT data. Possible movement patterns of the osteotomy fragments were rotations, sagittal and transversal movements or combinations of these. The program then allows the calculation of anatomical distances on the screen in a 1:1 relation. Normative values according to age and pathological anatomy determine the degree of displacement. The program calculates the new position of the osteotomy fragments and transfers the data of the segment movement to the original CT data. 3D visualization of bone and soft tissue contours have been produced with an acceptable quality on a workstation for the demonstration and visual understanding of the surgical plan. Evaluation of a postoperative CT showed that the amount of movement and size of bone resection in the simulation was slightly overestimated rather than underestimated. This was also dependent on the complexity of the pathological anatomy and on how experienced the surgeon was. The use of 3D simulation programs allows a better understanding of the pathological anatomy in all dimensions, and in many cases enables limitations to be recognized in advance. The public domain program makes a major contribution to the quality of orthognathic and craniofacial surgical planning through cost-free usability, and supports continuous development and exchange of experience.


SIRT2 inhibition activates hypoxia-inducible factor 1α signaling and mediates neuronal survival.
Sirtuins are deacetylases dependent on nicotine adenine dinucleotide (NAD) and take an important role in metabolism and aging. In mammals, there are seven sirtuins (SlRTl-7), and only SIRT2 is predominantly localized in cytoplasm. Under hypoxic environments, metazoan organisms must maintain oxygen homeostasis to survive. Hypoxia conditions induce reduction the ratio of NAD+/NADH, and aberrant increases or decreases in cellular O2 concentration induced excessive reactive oxygen species generation. Here, we report that inhibition of SIRT2 stabilizes hypoxia-inducible factor 1α (HIF-1α) protein levels and enhances hypoxia-responsive element-containing gene expression. We also show that the SIRT2 inhibitor AGK2 induces VEGF and HO-1 gene expression and protects neuronal viability from oxidative stress. Our findings suggest that SIRT2 negatively regulates HIF-1α signaling, indicating that SIRT2 inhibition may be a useful treatment strategy following ischemic injury.


Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome.
The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)-infected patients. A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011-2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023-1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660-10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR, 2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.


[Study on the association among total immunoglobulin E and eosinophil in nasal polyp].
To explore the expression of total immunoglobulin E(IgE) and eosinophil in nasal polyp and their roles in the pathogenesis of nasal polyp. Thirty eight patients with nasal polyp and 15 control cases were chosen. All samples were stained with Chromotrope 2R histochemical and SP immunohistochemical method separately to examine eosinophil and total IgE+ cells in nasal polyp. (1) The level of total IgE and eosinophil in nasal polyp was all significantly higher than that in normal control specimens (P < 0.01). (2) The positive correlation of total IgE and eosinophil was significant (r = 0.843, P < 0.01). Nasal polyp is a disease characterized by eosinophils infiltration. Type I allergic reaction mediated by IgE assemble and activate eosinophils which may play an important role in the infiltration pathogenesis of nasal polyp.


Is Breast Implant-Associated Anaplastic Large Cell Lymphoma Better Classified as a Lymphoproliferative Disorder and How Surgeons Reduce Risk?
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a complex topic with evolving classification and etiology. Commonalities between BIA-ALCL and lymphoproliferative disorders exist, suggesting that BIA-ALCL may be better represented on a spectrum of disease from benign effusion to malignant metastatic lymphoma. Meticulous sterile surgical technique, involving the use of betadine-containing irrigation, should be used to decrease the biological burden introduced into the surgical field and possibly prevent future incidences of BIA-ALCL.


Spatial scale effects of integrated landscape indicators on river water quality in Chaohu Lake basin, China.
Climate change and rapid urbanization have changed the characteristics of basin landscapes. Non-point-source (NPS) pollution affects river water quality. Exploring the impact of landscapes on river water quality is crucial for the control of water pollution in a basin. Current researchers focus on the impact of landscape pattern change on NPS pollution in the basin, but few consider climate, terrain, soil, and other geographical factors. In this study, we selected a subtropical agricultural basin in China named Chaohu Lake basin as the study area, added precipitation, soil erosion resistance, and slope to the original landscape pattern indicators. We quantified the spatial scale effect and seasonal dependence of integrated landscape indicators on water quality and comprehensively analyzed the optimal spatial scale and key landscape indicators. According to the nonlinear relationship between the key landscape indicators and river nutrients, we also determined the Type-1 threshold values of key landscape indicators for water quality protection in the basin. The results showed that the rivers in Chaohu Lake basin were mainly polluted by nitrogen and phosphorus. The strength of interpretation of the integrated landscape indicators of river water quality increased with riparian zone width. We determined the subbasin scale to be the optimal spatial scale. The key landscape indicators affecting water quality in the wet season at the optimal scale were precipitation and aggregation index of construction land (AIbul), whereas those in the dry season were AIbul and COHESION. The interpretation of the key landscape indicators in the wet season was slightly higher than that in the dry season. The above conclusions provide a scientific reference for NPS pollution control and water quality protection in subtropical agricultural basins.


The effect of chemical stimulation of esophageal mucosa on citric acid induced cough and specific airway resistance in guinea pig.
Gastroesophageal reflux disease is one of the most common causes of chronic cough. The mechanism of the cough initiation in these patients remains unresolved. This study was designed to investigate the effect of intraesophageal (IE) administration of capsaicin on cough and specific airway resistance (Saw) in guinea pigs. Male TRIK strain guinea pigs were used. In the first experiment 12 controls received IE saline, 9 animals (group 1) received IE capsaicin (400 microM, 0.2 ml) and 12 guinea pigs (group 2) received IE capsaicin (400 microM, 0.2 ml) 24 hours after IE administration of hydrochloric acid (3 M, 0.2 ml). Cough induced by inhalation of citric acid (CA) and Saw was determined after IE administration of saline in controls and capsaicin in groups 1 a 2. In the second experiment, CA induced cough was determined in guinea pigs (n=13) in the beginning of the study (control response), after NaOH (1 M, 0.2 ml) was administered IE. One week later in conditions of corrosive esophagitis CA induced cough was determined after IE administration of capsaicin (cough during esophageal stimulation). There was no difference in CA induced cough between controls, group 1 and 2 (p=0.98). Saw was hot affected by IE capsaicin stimulation and CA inhalation in group 1 and group 2. There was no difference found between control cough response and those induced after IE capsaicin in animals with corrosive esophagitis (p=0.75). Esophageal stimulation with capsaicin did not trigger and/or modulate CA induced cough and Saw in guinea pigs models. (Fig. 5, Ref. 22.)


Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine.
Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.


Characterization of changes to the mechanical properties of arteries due to cold storage using nanoindentation tests.
Understanding the effect of cold storage on arterial tissues is essential in various clinical and experimental practices. Cold storage techniques could significantly affect the post-cryosurgical or post-cryopreservation mechanical behavior of arteries. Previously, arteries were considered homogenous and elastic and the changes in material properties due to cold storage were inconclusive. In this study, using a custom-made nanoindentation device, changes to the local viscoelastic properties of porcine thoracic aorta wall due to three common storage temperatures (+4, -20, and -80 °C) within 24 h, 48 h, 1 week, and 3 weeks were characterized. The changes to both elastic and relaxation behaviors were investigated considering the multilayer, heterogeneous nature of the aortic wall. The results showed that the average instantaneous Young's modulus (E) of +4 °C storage samples decreased while their permanent average relaxation amplitude (G (∞)) increased and after 48 h these changes became significant (10 and 13% for E and G (∞), respectively). Generally, in freezer storage, E increased and G (∞) showed no significant change. In prolonged preservation (>1 week), the results of -20 °C showed significant increase in E (20% after 3 weeks) while this increase for -80 °C was not significant, making it a better choice for tissue cold storage applications.


Ultrasonic wound debridement.
Current management of hand injuries includes debridement by abrasive scrubbing with anti-bacterial detergents, surgical excision, or pressure irrigation. A rat model with a contaminated laceration was used to study the efficacy of ultrasonic debridement to diminish bacterial counts and particulate matter in open wounds. Ultrasonic debridement of hand wounds has several advantages over the current methods of wound debridement. These include a technically simple procedure that is effective in the removal of particulate matter and the reduction of bacterial counts (p less than 0.005). In addition there was no blood loss and no detectable damage of viable tissues as evaluated by electron microscopy. This technique may prove to be a significant advance in the early management of hand wounds.