Variations in uterine innervation during the estrous cycle in rat.
Uterine innervation undergoes profound remodeling during puberty, pregnancy, and after parturition. However, the extent to which uterine innervation may change during the estrous cycle is uncertain. The objective of the present study was to determine whether nerve fiber density of the uterine horn is altered during the estrous cycle and, if so, which subpopulations are affected. Immunostaining for the pan-neuronal marker protein gene product (PGP) 9.5 revealed fibers within the vascular zone, myometrium, and endometrium, with greater density in the ovarian and cervical regions than in the middle. In most structures, nerve density was reduced during estrus. This could not be accounted for by increased target volume, as the reduction in longitudinal muscle innervation persisted after correction for changes in target size. Immunostaining for vasoactive intestinal polypeptide-immunoreactive parasympathetic nerves revealed fibers associated predominantly with the vascular zone and circular muscle within the cervical region. No cyclical variation was detected. Calcitonin gene-related peptide-immunoreactive nerves were present within all structures, and density was highest at the ovarian end. These fibers also did not vary significantly through estrous. Dopamine beta-hydroxylase-immunoreactive sympathetic nerves innervated all structures, with greater density in the ovarian end. These fibers were reduced substantially during estrus, but the decline was also significant in proestrus, thus preceding that detected by using the pan-neuronal marker. We conclude that the estrous cycle in rat is accompanied by structural remodeling of sympathetic nerves by way of retraction or degeneration of terminal fibers during estrus. The structural loss of the terminal axon apparently is preceded by depletion of catecholamine-synthesizing enzyme.


Differences between platelet phosphoinositide metabolism stimulated by thrombin or SFLLRN are not accounted for by interaction of thrombin with glycoprotein Ib.
The formation of inositol phosphates was compared in aspirin-treated, washed human platelets suspended in Tyrode's-albumin solution containing 2 mM calcium and stimulated with SFLLRN (thrombin receptor-activating peptide) or thrombin. SFLLRN (20 microM) and thrombin (1 U/ml) resulted in maximal irreversible aggregation and 80-90% secretion of dense granule contents. SFLLRN (50-100 microM) caused larger increases at 10 sec than 20 microM SFLLRN in the formation of inositol trisphosphate (IP3, measured as [3H]inositol label). These increases were not significantly less than those caused by thrombin (1 unit/ml). However, whereas the labeling of IP3 increased from 10-60 sec with thrombin, with SFLLRN it was much less at 60 sec than that at 10 sec. The decrease was not due to degradation of SFLLRN by ectopeptidases, since it was not prevented by amastatin, an inhibitor of ectopeptidases. Degradation of glycoprotein Ib (GPIb) with an O-sialoglycoprotein endopeptidase did not affect the thrombin-stimulated labeling of inositol phosphates, indicating that binding to GPIb is not involved in the sustained thrombin-induced formation of inositol phosphates. The finding that the thrombin-stimulated formation of IP3 was not dependent on Ca2+ in the medium (EGTA added) indicates that the transient SFLLRN-induced formation of IP3 is not due to failure to cause Ca2+ influx. The finding that formation of IP3 was transient in SFLLRN-stimulated platelets, whereas platelet aggregation and secretion were maximal, indicates that the sustained activation of phospholipase C caused by thrombin may have roles related to later processes in which platelets participate.


Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT(2C) receptor knockout mice.
Several studies have suggested a close interaction between serotonin (5-HT) and BDNF; however, little is known of the specific relationship between BDNF and the 5-HT(2C) receptor. Therefore, in this study we investigated BDNF expression in 5-HT(2C) receptor knockout mice (5-HT(2C) KO). We also assessed functional consequences of any changes in BDNF using a behavioral test battery. Western blot analysis demonstrated a significant 2.2-fold increase in the expression of the mature form of BDNF in 5-HT(2C) KO mice when compared with wild-type controls (WT) in the hippocampus (P = 0.008), but not frontal cortex or striatum. No differences in the expression of the pro-BDNF isoform were found, and the ratio of mature/pro BDNF was significantly increased in 5-HT(2C) KO (P = 0.003). BDNF mRNA expression in the hippocampus was not different between the genotypes. Hence, increased mature BDNF levels in 5-HT(2C) KO hippocampus are most likely due to increased extracellular cleavage rates of pro-BDNF to its mature form. Protein expression of the BDNF receptor, tropomycin-related receptor B (TrkB), was also unchanged in the hippocampus, frontal cortex and striatum. With repeated training in a 10-day win-shift radial arm maze task, 5-HT(2C) KO and WT showed similar decreases of the number of working memory and reference memory errors. In addition, no genotype specific differences were observed for passive or active avoidance learning. 5-HT(2C) KO showed modest locomotor hyperactivity but no differences in tests for anxiety, sensorimotor gating, or depressive-like behaviors; however, in the tail suspension test 5-HT(2C) KO showed significantly reduced climbing (P < 0.05). In conclusion, loss of 5-HT(2C) receptor expression leads to a marked and selective increase in levels of the mature form of BDNF in the hippocampus. Despite this marked increase, 5-HT(2C) KO show only subtle behavioral changes.


AAOA allergy primer: immunodeficiency.
Primary immunodeficiency is rare but should be considered in patients who present to the otolaryngologist with recurrent, severe, or treatment refractory infections. Recent literature and consensus statements on immunodeficiency were reviewed for clinically important information of relevance to otolaryngologists. The most common and most relevant immunodeficiencies are humoral deficiencies with inadequate antibody production or an impairment in the production of specific antibody after antigen exposure. For otolaryngologists the most important immunodeficiencies include immunoglobulin A (IgA) deficiency, common variable immunodeficiency (CVID), and specific antibody deficiency. Simple screening tests can be used by the otolaryngologist to exclude the most common immunodeficiencies. The general treatment approach to patients with these immunodeficiencies includes airway hygiene, early and aggressive treatment of infections, immunization, and antibody replacement therapy. By virtue of their scope of practice, otolaryngologists are in a position to recognize and initiate the diagnostic workup of patients with immunodeficiency. Patients with a diagnosed primary immunodeficiency are best managed in a multidisciplinary manner with close cooperation among the otolaryngologist, immunologist, and other specialists that are involved in treating these multisystem diseases.


[Associations of chronic obstructive pulmonary disease, bronchial asthma, and type 1 diabetes mellitus].
The aim of the study was to clarify the relationships between bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and type 1 diabetes mellitus. Reduced prevalence of concomitant BA and DM1 suggests inverse relation between the two conditions and their mutually exclusive nature. The problem needs further studies. Taking into account age-specific and other features of COPD and DM1 pathological processes elucidation of their interrelation appears impractical.


Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma.
Ki67 is a nuclear antigen significantly correlated with degree of malignancy in human non-Hodgkin lymphomas. We wanted to assess the ability of flow cytometric evaluation of Ki67 index (Ki67I) in differentiating the grade of malignancy in canine lymphomas. Ki67I was determined on lymph node aspirates of 90 immunophenotyped lymphomas classified according to the updated Kiel classification: 80 high grade (HG, 62 B cell and 18 T cell) and 10 low grade (LG, 3 B cell and 7 T cell) lymphomas. HG lymphomas showed significantly higher Ki67I compared with LG lymphomas (P < 0.0001). A significant difference in HG lymphomas was detected between B- and T-immunophenotypes. Receiver operating characteristic (ROC) curve highlighted a high accuracy of Ki67I in recognizing HG lymphomas [area under the curve (AUC) = 99.4] and a cut-off value of 12.2% was established (sensitivity = 96.3% and specificity = 100%). Thus, we suggest the combination of Ki67I flow cytometric determination and immunophenotype as a reliable tool to classify canine lymphomas.


Mucosa-associated bacteria in two middle-aged women diagnosed with collagenous colitis.
To characterize the colon microbiota in two women histologically diagnosed with collagenous colitis using a culture-independent method. Biopsies were taken from the ascending colon and the total DNA was extracted. Universal bacterial primers were used to amplify the bacterial 16S rRNA genes. The amplicons were then cloned into competent Escherichia coli cells. The clones were sequenced and identified by comparison to known sequences. The clones could be divided into 44 different phylotypes. The microbiota was dominated by Firmicutes and Bacteroidetes. Seven phylotypes were found in both patients and constituted 47.5% of the total number of clones. Of these, the most dominating were clones similar to Bacteroides cellulosilyticus, Bacteroides caccae, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides dorei within Bacteroidetes. Sequences similar to Faecalibacterium prausnitzii and Clostridium citroniae were also found in both patients. A predominance of potentially pathogenic Bacteroides spp., and the presence of clones showing similarity to Clostridium clostridioforme were found but the overall colon microbiota showed similarities to a healthy one. Etiologies for collagenous colitis other than an adverse bacterial flora must also be considered.


Silicosis in barium miners.
Four men who mined barytes in Scotland and who developed pneumoconiosis are described. Three developed progressive massive fibrosis, from which two died; and one developed a nodular simple pneumoconiosis after leaving the industry. The radiological and pathological features of the men's lungs were those of silicosis and high proportions of quartz were found in two of them post mortem. The quartz was inhaled from rocks associated with the barytes in the mines. The features of silicosis in barium miners are contrasted with the benign pneumoconiosis, baritosis, that occurs in workers exposed to crushed and ground insoluble barium salts. Diagnostic difficulties arise when silicosis develops in workers mining minerals known to cause a separate and benign pneumoconiosis. These difficulties are compounded when, as not infrequently happens, the silicotic lesions develop or progress after exposure to quartz has ceased.


Co-location of air capture, subseafloor CO2 sequestration, and energy production on the Kerguelen plateau.
Reducing atmospheric CO2 using a combination of air capture and offshore geological storage can address technical and policy concerns with climate mitigation. Because CO2 mixes rapidly in the atmosphere, air capture could operate anywhere and in principle reduce CO2 to preindustrial levels. We investigate the Kerguelen plateau in the Indian Ocean, which offers steady wind resources, vast subseafloor storage capacities, and minimal risk of economic damages or human inconvenience and harm. The efficiency of humidity swing driven air capture under humid and windy conditions is tested in the laboratory. Powered by wind, we estimate ∼75 Mt CO2/yr could be collected using air capture and sequestered below seafloor or partially used for synfuel. Our analysis suggests that Kerguelen offers a remote and environmentally secure location for CO2 sequestration using renewable energy. Regional reservoirs could hold over 1500 Gt CO2, sequestering a large fraction of 21st century emissions.


Intergrowth of components and ramps in coffin-shaped ZSM-5 zeolite crystals unraveled by focused ion beam-assisted transmission electron microscopy.
Scanning electron microscopy, focused ion beam (FIB), and transmission electron microscopy are combined to study the intergrowth of 90° rotational components and of ramps in coffin-shaped ZSM-5 crystals. The 90° rotational boundaries with local zig-zag features between different intergrowth components are observed in the main part of crystal. Also a new kind of displacement boundary is described. At the displacement boundary there is a shift of the unit cells along the boundary without a change in orientation. Based on lamellae prepared with FIB from different positions of the ramps and crystal, the orientation relationships between ramps and the main part of the crystal are studied and the three-dimensional morphology and growth mechanism of the ramp are illustrated.


Underuse of invasive procedures among Medicaid patients with acute myocardial infarction.
The purpose of this study was to determine whether underuse of cardiac procedures among Medicaid patients with acute myocardial infarction is explained by or is independent of fundamental differences in age, race, or sex distribution; income, coexistent illness; or location of care. Administrative data from 226 hospitals in New York were examined for 11,579 individuals hospitalized with a primary diagnosis of acute myocardial infarction. Use of various cardiac procedures was compared among Medicaid patients and patients with other forms of insurance. Medicaid patients were older, were more frequently African American and female, and had lower median household incomes. They also had a higher prevalence of hypertension, diabetes, lung disease, renal disease, and peripheral vascular disease. After adjustment for these and other factors, Medicaid patients were less likely to undergo cardiac catheterization, percutaneous transluminal coronary angioplasty, and any revascularization procedure. Factors other than age, race, sex, income, coexistent illness, and location of care account for lower use of invasive procedures among Medicaid patients. The influence of Medicaid insurance on medical practice and process of care deserves investigation.


Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity.
We have used multiple-amino acid replacement mutagenesis to examine the roles of the TCR homologues of Ig complementarity-determining regions (CDR) and framework sequences in Ag-MHC and Staphylococcus aureus enterotoxin reactivity. In the three cases examined, transplantation of Ig CDR3 homologues between I-Ek-restricted TCR that recognize distinct peptides did not result in transfer of peptide reactivity. Thus the structural context of the CDR3 loops, e.g., both neighboring CDR and the V beta structure, must play a crucial, albeit supporting, role in ligand recognition. The extreme lability of this context was also shown by the fact that transplantation of the CDR1, -2, and -3 loops from the beta chain of 5C.C7 onto a V beta 1 framework failed to transfer MHC-peptide specificity even when the TCR-alpha chains were identical. In contrast, superantigen reactivity was readily transferred in several cases, with CDR2 transplants conferring strong staphylococcal enterotoxin B and A reactivity and CDR1 transplants yielding weak reactivities. This suggests that bacterial (and perhaps other) superantigens bind to many of the same regions of the TCR V beta that are believed to interact with MHC molecules. These regions of V beta may be ideal targets for superantigen binding precisely because they interact with MHC molecules and thus may be relatively conserved.


CT features of pulmonary embolism in patients with COVID-19 pneumonia.
The aim of this study was to describe the Computed Tomography (CT) features of pulmonary embolism in patients hospitalized for acute COVID-19 pneumonia and to evaluate the prognostic significance of these features. This retrospective study included 110 consecutive patients who were hospitalized for acute COVID-19 pneumonia and underwent pulmonary computed tomography angiography (BTPA) on the basis of clinical suspicion. The diagnosis of COVID-19 infection was determined by CT findings typical of COVID-19 pneumonia and/or a positive result of a reverse transcriptase-polymerase chain reaction test. Of the 110 patients, 30 (27.3%) had acute pulmonary embolism and 71 (64.5%) had CT features of chronic pulmonary embolism. Of the 14 (12.7%) patients who died despite receiving therapeutic doses of heparin, 13 (92.9%) had CT features of chronic pulmonary embolism and 1 (7.1%) of acute pulmonary embolism. CT features of chronic pulmonary embolism were more common in deceased patients than in surviving patients (92.9% vs. 60.4%, p=0.01, respectively). Low oxygen saturation and high urine microalbumin creatinine ratio at admission in COVID-19 patients are important determinants of mortality after adjusting for sex and age in logistic procedures. CT features of chronic pulmonary embolism are common in COVID-19 patients undergoing Computed Tomography Pulmonary Angiography (CTPA) in the hospital. The coexistence of albuminuria, low oxygen saturation and CT features of chronic pulmonary embolism at admission in COVID-19 patients may herald fatal outcomes.


The Vav-Rac1 pathway in cytotoxic lymphocytes regulates the generation of cell-mediated killing.
The Rac1 guanine nucleotide exchange factor, Vav, is activated in hematopoietic cells in response to a large variety of stimuli. The downstream signaling events derived from Vav have been primarily characterized as leading to transcription or transformation. However, we report here that Vav and Rac1 in natural killer (NK) cells regulate the development of cell-mediated killing. There is a rapid increase in Vav tyrosine phosphorylation during the development of antibody-dependent cellular cytotoxicity and natural killing. In addition, overexpression of Vav, but not of a mutant lacking exchange factor activity, enhances both forms of killing by NK cells. Furthermore, dominant-negative Rac1 inhibits the development of NK cell-mediated cytotoxicity by two mechanisms: (a) conjugate formation between NK cells and target cells is decreased; and (b) those NK cells that do form conjugates have decreased ability to polarize their granules toward the target cell. Therefore, our results suggest that in addition to participating in the regulation of transcription, Vav and Rac1 are pivotal regulators of adhesion, granule exocytosis, and cellular cytotoxicity.


Anatomic Double Bundle single tunnel Foreign Material Free ACL-Reconstruction - a technical note.
The anterior cruciate ligament (ACL) consists of two bundles, the anteromedial (AM) and posterolateral bundle (PM). Double bundle reconstructions appear to give better rotational stability. The usual technique is to make two tunnels in the femur and two in the tibia. This is difficult and in small knees may not even be possible. We have developed a foreign material free press fit fixation for double bundle ACL reconstruction using a single femoral tunnel ((R)). This is based on the ALL PRESS FIT ACL reconstruction. It is suitable for the most common medium and, otherwise difficult, small sizes of knees. Using diamond edged wet grinding hollow reamers, bone cylinders in different diameters are harvested from the implantation tunnels of the tibia and femur and used for the press fit fixation. Using the press fit technique the graft is first fixed in tibia. It is then similarly fixed under tension in the femoral side with the knee in 120 degree flexion. This is called Bottom To Top Fixation (BTT). On extending the knee the graft tension is self adapting. Depending on the size of the individual knee, the diameter of the femoral bone plug is varied from 8 to 13 mm to achieve an anatomic spread with a double bundle-like insertion. The tibia tunnel can be applied with two 7 or 8 mm diameter tunnels overlapping to a semi oval tunnel between 10 to 13 mm. Since May 2003 we have carried out ACL-reconstructions with Hamstring grafts without foreign material using the ALL PRESS FIT technique. Initially, an 8 mm press fit fixation was used proximally with good results. Since April 2008, the range of diameters was increased up to 13 mm. The results of the Lachman tests have been good to excellent. Results of the Pivot shift test suggested more stability with femoral broader diameters of 9,5 to 13 mm. The foreign material free fixation of ham-string in the ALL PRESS FIT Bottom To Top Fixation is a successful method for ACL Reconstruction. The Diamond Instruments and tubed guiding devices are precise, reliable and easy to manage. On this basis a double bundle reconstruction is achieved using a single tunnel. A broad anatomic femoral insertion with autogenous bone plugs inserted near the cortex seems to improve rotational stability.


Differential expression of Oct3/4 in human breast cancer and normal tissues.
Oct3/4, a transcription factor specifically expressed in mammalian totipotent embryonic stem and germ cells, has a critical role in the regulation and maintenance of pluripotency and self-renewal. However, reactivation of Oct3/4 expression is observed in several human breast cancer cell lines, but not in non‑malignant cells. To examine Oct3/4 expression in human primary breast carcinomas and normal breast tissues, we obtained breast tumor tissues from 28 patients and normal breast tissues from 9 women. According to quantitative polymerase chain reaction, all of the tumor tissues, irrespective of tumor type or clinicopathological status, expressed Oct3/4 mRNA at 10- to 100- fold higher levels than that in the normal breast tissues. Expression of the Oct3/4 protein in tumors was confirmed by western blot analysis and immunofluorescent staining. Additionally, rapid amplification of cDNA ends and DNA sequencing revealed expression of multiple Oct4 gene transcripts from chromosome 6 (POU5F1) in normal breast tissues and the non‑malignant breast epithelial cell line MCF‑10A; by contrast, the breast tumors and malignant breast cancer cell line MCF‑7 predominantly expressed transcripts of an Oct4-like gene (POU5F1B) from chromosome 8, which was termed Oct3 in the current study. The deduced amino acid sequences of full-length Oct3 and Oct4 are 96% identical. The findings of the current study indicated that Oct3, rather than Oct4, may serve as a novel clinical marker and a potential target for gene-specific therapy of breast cancer.


Wigner crystal physics in quantum wires.
The physics of interacting quantum wires has attracted a lot of attention recently. When the density of electrons in the wire is very low, the strong repulsion between electrons leads to the formation of a Wigner crystal. We review the rich spin and orbital properties of the Wigner crystal, in both the one-dimensional and the quasi-one-dimensional regimes. In the one-dimensional Wigner crystal the electron spins form an antiferromagnetic Heisenberg chain with exponentially small exchange coupling. In the presence of leads, the resulting inhomogeneity of the electron density causes a violation of spin-charge separation. As a consequence the spin degrees of freedom affect the conductance of the wire. Upon increasing the electron density, the Wigner crystal starts deviating from the strictly one-dimensional geometry, forming a zigzag structure instead. Spin interactions in this regime are dominated by ring exchanges, and the phase diagram of the resulting zigzag spin chain has a number of unpolarized phases as well as regions of complete and partial spin polarization. Finally we address the orbital properties in the vicinity of the transition from a one-dimensional to a quasi-one-dimensional state. Due to the locking between chains in the zigzag Wigner crystal, only one gapless mode exists. Manifestations of Wigner crystal physics at weak interactions are explored by studying the fate of the additional gapped low-energy mode as a function of interaction strength.


Digesta retention patterns in geese (Anser anser) and turkeys (Meleagris gallopavo) and deduced function of avian caeca.
Although it is well-known that retrograde transport of urine fills the caeca of birds with fluid and small particles, the function of avian caeca is still not fully understood. We measured mean retention times (MRT) of solute (cobalt-EDTA, Co), small particle (<2mm, chromium-mordanted fibre, Cr) and large particle (8mm, cerium-marked fibre, Ce) markers in geese (Anser anser) and turkeys (Meleagris gallopavo) fed alfalfa pellets ad libitum. Intake did not differ between species. Turkeys had longer MRT for all markers (Co: 10.4 vs. 3.2h; Cr 23.3 vs. 2.9h; Ce 9.5 vs. 2.1h), achieved a higher fibre digestibility, and had a higher calculated dry matter gut fill. Thus, geese and turkeys correspond to the typical dichotomy of good fliers vs. poor fliers/flightless species in avian herbivores. Because uric acid is fermented much faster by microbes than fibre, the ultimate cause of short-MRT digesta retention in avian caeca as in geese is possibly rather uric acid than fibre fermentation. The numerical differences between marker MRT in geese correspond to a colonic separation mechanism that delays the excretion of fluids more than small and again more than large particles. In contrast to geese, turkeys excreted solid and liquid (caecal) faeces. Liquid faeces contained less fibre and more crude protein than solid faeces and accounted for the excretion of 7, 25 and 34% of Ce, Co and Cr markers. Marker excretion patterns and MRT for liquid faeces (Co 15 vs. Cr 50h) suggest that small particles did not simply move in parallel to fluids, but were retained selectively by being trapped in colonic digesta upon expulsion from caeca, with subsequent repeated retrograde transport into caeca with the next batch of urine. Given the absence of coprophagy in birds (in contrast to small mammalian herbivores), such a delay of small (microbial) particle escape from the caeca appears reasonable.


The volunteer spirit is alive and well at Scottish Rite Hospital. Interview by Melissa Gaskill.
Today, Scottish Rite Hospital for Crippled Children in Dallas serves 10,000 Texas children with the help of 600 or so volunteers who log about 82,000 hours a year. This astonishing volunteer program has earned the hospital awards and recognition--including this year's AHA award for the outstanding volunteer program in Region 7--and has helped create the warm, team atmosphere that sets this hospital apart. President J.C. Montgomery takes pride in his volunteers and in the other part of that team, the paid staff. A member of the Texas Hospital Association board of trustees, he is also on the board of the Texas Hospital Education and Research Foundation and chair of that group's Investment Committee. Health Texas recently visited with Montgomery about the hospital and the volunteer program.


Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience.
Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support.


Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.
Together, acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Here we show that ASICs were reversibly inhibited by activation of GABA(A) receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A) receptor-mediated currents. Moreover, activation of the GABA(A) receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A) receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A) receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A) receptors, also modified ASICs in spinal neurons. We conclude that GABA(A) receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.


SPECIFIC CORNEAL PARAMETERS AND VISUAL ACUITY CHANGES AFTER CORNEAL CROSSLINKING TREATMENT FOR PROGRESSIVE KERATOCONUS.
To evaluate the effect of crosslinking (CXL) therapy on the change in the quality of visual acuity and the change in the topographic properties of the cornea - curvature, pachymetry, and change of astigmatism, coma abberation and CLMIaa (Cone Localisation and Magnitude Index). A retrospective analytical study included 29 eyes of 24 patients who had progressed in the last 12 months and were suitable candidates for CXL surgery. The monitored parameters were the steepest, flatest and mean anterior instantaneous curvature (AICS, AICF, AICM) and the steepest, flatest and mean posterior instantaneous curvature (PICS, PICF, PICM) of the cornea, corneal thickness in the centre of the cornea (PACHC) and in the thinnest point of the cornea (PACHT), corneal astigmatism (ASTIG). coma (COMA), Cone Localization and Magnitude Index (CLMIaa) and uncorrected distance visual acuity (UDVA) with corrected distance visual acuity (CDVA). Data were analysed before surgery and 12 months after surgery. The AIC, COMA, CLMIaa and ASTIG parameters were analysed by paired t test. As the parameters of UDVA, CDVA, PIC and PACH did not meet the conditions of normal distribution, the Wilcoxon test was used to investigate the change in these parameters after CXL. Twelve months after the procedure, we recorded an improvement in UDVA (p = 0.371) and CDVA (p = 0.825), an increase in PICS, PICF and PICM (p = 0.902; p = 0.87 and p = 0.555), a decrease in PACHCC (p = 0.294) and a decrease in CLMIaa (p = 0.113) that did not reach statistical significance. The decrease in PACHT (p = 0.027), decrease in COMA (p = 0.037) and decrease in anterior corneal curvature of AICS, AICF and AICM were statistically significant (p = 0.019; p = 0.010 and p = 0.005). The decrease in the value of astigmatism did not show statistical significance, as p = 0.297. CXL corneal therapy has been shown to be an effective method to stabilize the cornea in progressive keratoconus, and to improve the higher order of coma. This contributes to the possible improvement of UDVA and CDVA.


Baroreflex control of heart rate in rats with heart failure after myocardial infarction: effects of captopril.
Activation of the renin-angiotensin and sympathetic nervous systems in heart failure may result in altered baroreflex control of heart rate. To determine the specific effects of treatment with captopril on baroreceptor dysfunction in heart failure, baroreflex control of heart rate was measured in conscious rats with heart failure 6 weeks after ligation of the left coronary artery. Plasma norepinephrine was measured as a reflection of sympathetic nervous system activity. After bolus injections of phenylephrine (2-50 micrograms/kg) and nitroprusside (2-50 micrograms/kg), the arterial baroreflex was analyzed by fitting percentage of mean arterial pressure changes and heart rate changes to a logistic regression function. There were no differences in baroreflex function between normal and sham-operated rats. Plasma norepinephrine was increased (P < .05) in the heart-failure rats and did not change with captopril treatment. In untreated rats, heart failure increased (P < .05) the centering point by 900%, threshold by 243% and saturation by 89%, whereas decreasing (P < .05) the operational point by 73%. There was a decrease (P < .05) in the nitroprusside-related gain and an increase (P < .05) in phenylephrine-related gain, but the overall baroreflex gain was not changed. In heart-failure rats, captopril increased (P < .05) threshold, saturation and centering point and decreased (P < .05) operational point and nitroprusside- and phenylephrine-related gain abnormalities. The increase in operational point and decreases in threshold, saturation, centering point and phenylephrine-related gain were the results of a specific interactive effect of captopril in heart failure (P = .0033, .0176, .0509, .0217 and .0567, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Risk factors for acute pain and its persistence following breast cancer surgery.
Although more severe acute postoperative pain increases the risk of chronic pain following breast cancer surgery, few studies have examined the characteristics of patients who develop greater acute pain. To identify risk factors for acute pain and its persistence one month following breast cancer surgery, a sample of 114 women scheduled for breast cancer surgery was assessed preoperatively for demographic, clinical, and emotional functioning variables that were hypothesized to be associated with acute pain severity. Clinically meaningful postoperative pain was assessed at follow-up interviews 2, 10, and 30 days after surgery. In univariate analyses, the risk of clinically meaningful acute pain was increased among women who were younger, unmarried, had more invasive surgeries, and had greater preoperative emotional distress. In multiple logistic regression analyses, greater preoperative anxiety was the only variable that made an independent contribution to predicting clinically meaningful acute pain at 2 days after surgery whereas younger age, being unmarried, and preoperative anxiety each made an independent contribution to predicting clinically meaningful acute pain that persisted from 2 to 30 days after surgery. These results increase understanding of neurobiologic mechanisms and psychosocial processes that contribute to the development of acute pain following breast cancer surgery and have implications for the development of interventions to prevent it.


Demonstrating the Impact of Cognitive CEO on Firms' Performance and CSR Activity.
One aspect of entrepreneurship psychology also clarifies individual characteristics. Drawing from entrepreneurship psychology, the concept of a cognitive CEO has been formulated using the DAE statistical technique. The study elucidates that cognitive CEOs not only boost SME performance but also invigorate CSR activity. Data for listed SMEs for the years 2016-2018 are analyzed through the panel regression technique. Significantly, the study demonstrates that CEO age is positively interlinked with the growth and CSR activity of the firm. Moreover, the empirical underpinning of the results also reveals that state-owned enterprises and firms with high total assets prefer cognitive CEOs, who accelerate the firm's value and invigorate CSR activity. The number of independent directors is analyzed as a moderator and is concluded to be an intensifier for both SME growth and CSR activity. Finally, 2SLS instrumental panel regression is used to validate the veracity of the empirical results.


Scanning Electron Microscopy of Vulval Cones of Heterodera glycines and Three Related Cyst Nematode Species.
Vulval cones of four closely related Heterodera species - H. glycines (races 1-5), H. lespedezae, H. schachtii, and H. trifolii - were examined using scanning electron microscopy. Numbers of dorsal and ventral radial ridges, total radial ridges, perineal ridges, and preanal ridges were useful in differentiating the five races of H. glycines and the other three species. Most of the populations differed significantly (P < 0.01) using the Waller-Duncan k-ratio t-test for mean separation of the five characters. H. glycines races 2, 4, and 5 were most similar. H. schachtii and H. trifolii were most dissimilar to each other and to H. lespedezae and H. glycines. Two additional qualitative characters were also useful in differentiating the populations. The shallower, shorter radial ridges of H. glycines provided a basis for separation from the other three species. Width and smoothness of the perineal ridges were useful in differentiating both races and species.


Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.
Daclizumab high-yield process (DAC HYP) is a humanized anti-CD25 monoclonal antibody that inhibits high-affinity interleukin-2 receptor signaling. The objective of this paper is to assess the proportion of DAC HYP- versus placebo-treated patients who were free from disease activity. SELECT was a randomized, double-blind, multicenter study of DAC HYP 150 mg or 300 mg, or placebo, administered subcutaneously every four weeks for 52 weeks. In this post-hoc analysis of the SELECT trial, 'disease-activity free' was defined as completion through week 52 without relapses or confirmed three-month disability progression (clinical), with no new/newly enlarging T2-hyperintense lesions and no new gadolinium-enhancing lesions at the week 52 scan (radiological). Primary analyses were based on logistic regression controlling for baseline characteristics. More DAC HYP-treated (39%, n = 156) versus placebo-treated patients (11%, n = 22) were disease-activity free (odds ratio (95% confidence interval), 6.18 (3.71-10.32); p < 0.0001). Furthermore, 77% and 48% of DAC HYP-treated patients were free from clinical or radiological disease activity, respectively, compared with 60% and 18% of placebo-treated patients. At one year, DAC HYP resulted in a meaningful increase in the proportion of relapsing-remitting MS patients who were disease-activity free versus placebo.


NEUTRAL SALTS: THE GENERALITY OF THEIR EFFECTS ON THE STABILITY OF MACROMOLECULAR CONFORMATIONS.
The effects of various neutral salts on the temperature of the thermally-induced denaturation of the globular protein ribonuclease are described and compared with the effects of these salts on helix-coil transition temperatures in other macromolecules. These agents affect the stability of the native form of macromolecules as diverse as ribonuclease, collagen, DNA, and myosin in very similar ways; salts such as KSCN and CaCl(2) serve as very potent general structural destabilizers or denaturants, while salts such as (NH(4))(2)SO(4) and K(2)HPO(4) strongly stabilize the native conformation. The effectiveness of the neutral salts as ribonuclease destabilizers is compared with that of urea and the guanidinium salts.


A prevalidation study on the in vitro skin irritation function test (SIFT) for prediction of acute skin irritation in vivo: results and evaluation of ECVAM Phase III.
A prevalidation study sponsored by the European Centre for the Validation of Alternative Methods (ECVAM) on in vitro tests for acute skin irritation is aimed at identifying non-animal tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union and OECD. This paper reports on Phase III for one of the methods, the skin integrity function test (SIFT), assessing the protocol performance of the SIFT, in terms of reproducibility and predictive ability, in three laboratories. The barrier function properties of excised mouse skin were determined using a set of 20 coded chemicals (10 I, 10 NI), using the endpoints of trans-epidermal water loss (TEWL) and electrical resistance (ER). The basis of the SIFT prediction model is if the ratios of the pre- and post-application values for either TEWL or ER are greater than five-fold, then the test chemical is deemed irritant (I). If the ratio of both parameters is less than five-fold then the chemical is deemed non-irritant (NI). Analysis of variance (ANOVA) indicated that the intra-lab reproducibility was acceptable but that the inter-lab reproducibility was not. Overall, the SIFT test under-predicted the irritancy of the test chemicals chosen for Phase III with an overall accuracy of only 55%. The sensitivity value (ability to correctly predict I) was only 30%. The specificity (ability to predict NI) of the test was better at 80%. A retrospective examination of the SIFT results was undertaken using Student's t-test and a significance level of P<0.05 to predict an irritant based on changes in the TEWL ratio values. This improved the predictivity of the SIFT test, giving a specificity of 60%, a sensitivity of 80% and an overall accuracy of 70%. Appropriate modifications to the prediction model have now been made and the SIFT will be re-examined in a new validation exercise to investigate the potential of this non-animal method to predict acute skin irritation potential.


Breast cancer survival in relation to sex and age.
Crude and relative survival rates were analyzed using data from 4,199 incident breast cancers in females and 39 breast cancers in males registered between 1974 and 1988 in the Cancer Registry of the Swiss Canton of Vaud. The relative survival rates were 0.94 for females and 0.95 for males at 1 year, 0.87 and 0.95 at 2 years, 0.71 and 0.75 at 5 years, and 0.57 and 0.65 at 10 years. In relation to age at diagnosis, among females the relative survival increased from 0.62 for cases diagnosed under the age of 35 years to 0.78 at the age of 45-49 years, decreased to 0.66-0.68 in the age group 50-59 years, and rose again to reach 0.76 at the age of 65-69 years, declining thereafter to 0.69 at the age range 80-84 years. This pattern was already evident during the first 2 years of follow-up and persisted up to 10 years after diagnosis, although somewhat less defined. For males, no significant difference was evident in relative survival between breast cancers diagnosed before or at the age of 65 years and over, and only the 10-year survival rate was apparently (though not significantly) lower at older ages. Thus, these population-based data show remarkable similarities in survival for female and male breast cancer, despite possible heterogeneities in diagnosis and ascertainment of the disease as well as differences in steroid hormone levels in the two sexes and possible differences in biological characteristics of the disease. Further, they confirm that breast cancer survival varies across subsequent age groups. This possibly reflects selection and modifying effects on incidence and survival of hormone dependency of a proportion of breast cancers, the growth of which could be accelerated during the premenopause and the survival favourably influenced by the decline in steroid hormone levels after the menopause.


Scaling laws and forecasting in athletic world records.
In this study, we analysed running world records and found that the mean speed of the race, mu, as a function of the record time, tau, can be described asymptotically by two well-defined scaling laws of the form mu approximately tau(-beta). There is a break in the scaling laws (approximately 1000 m) between the shorter and the longer races at a characteristic time of around 150-170 s, after which a new scaling regime emerges. This is the first occasion that this characteristic time has been clearly found in physical terms; we interpreted it as the transition time between the anaerobic and the aerobic energy expenditure of athletes. This phenomenon is independent of the athletes' sex and is also found in swimming races with similar values of the characteristic time. We also investigated the forecasting of world records using historical data. Using an approach based on the identification of non-Poissonian events for a sequence of temporal point processes, we found that the sequence of improvements in all athletic records from 1900 to the present day cannot be considered as a sequence of completely random events.


Multiple juvenile polyposis. A report of 2 cases.
Two cases of multiple juvenile polyposis in black boys aged 10 and 12 years are described. There was no history of polyposis in the families. In both patients the rectosigmoid part of the large bowel mainly was involved and was treated by colectomy. The first case showed a segment of sigmoid colon studded with polyps, which were predominantly sessile. The second case showed polypoid lesions throughout the sigmoid colon and rectum. This rare phenomenon has been infrequently reported among black people.


Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes.
The goal of these studies was to define the rate-limiting steps in the inactivation of type 2 iodothyronine deiodinase (D2). We examined the effects of ATP depletion, a lysosomal protease inhibitor, and an inhibitor of actin polymerization on D2 activity in the presence or absence of cycloheximide or 3,3', 5'-triiodothyronine (reverse T3, rT3) in rat pituitary tumor cells (GH4C1). We also analyzed the effects of the proteasomal proteolysis inhibitor carbobenzoxy- L-leucyl-L-leucyl-L-leucinal (MG132). The half-life of D2 activity in hypothyroid cells was 47 min after cycloheximide and 60 min with rT3 (3 nM). rT3 and cycloheximide were additive, reducing D2 half-life to 20 min. D2 degradation was partially inhibited by ATP depletion, but not by cytochalasin B or chloroquine. Incubation with MG132 alone increased D2 activity by 30-40% for several hours, and completely blocked the cycloheximide- or rT3-induced decrease in D2 activity. These results suggest that D2 is inactivated by proteasomal uptake and that substrate reduces D2 activity by accelerating degradation through this pathway. This is the first demonstration of a critical role for proteasomes in the post-translational regulation of D2 activity.


Standardized video-assisted retroperitoneal minilaparotomy surgery for 615 living donor nephrectomies.
To increase the rate of living kidney donation, the long-term safety of nephrectomy must be demonstrated to potential donors. We analyzed long-term donor outcomes and evaluated the standardization of surgical technique. We evaluated 615 donors who underwent Video-assisted minilaparotomy living donor nephrectomy (VLDN) at Yonsei Severance Hospital between 2003 and 2009. Perioperative data and predictors of outcomes were prospectively analyzed. The mean operative time and mean warm ischemia time were 192.7 and 2.2 min, respectively. Mean estimated blood loss was 195.3 ml. The mean post-transplant serum creatinine levels and Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate were 1.1 mg/dl and 68 ml/min/1.73 m(2) , respectively at 5 years after VLDN. The intra-operative and postoperative complication rate were 3.1% and 6.3%, respectively. Delayed renal function, 5-year graft survival, and complication rates of recipients were 1.1%, 98.4%, and 0.4%, respectively. Predictors of operative time were medical history, vessel anomaly, and surgeon experience (>50 cases). The single predictor of intra-operative complications was vessel anomaly. Standardized VLDN is feasible and safe. Our data on long-term outcomes can assist in demonstrating the long-term safety of donor nephrectomy to potential donors. To compare VLDN to other types of donor nephrectomy, a prospective multicenter study must be performed.


Extra-gastrointestinal stromal tumor presenting as hemorrhagic pancreatic cyst diagnosed by EUS-FNA.
Pancreatic gastrointestinal stromal tumors (GIST) are rare mesenchymal tumor with only 6 cases reported to date. We report a case of pancreatic GIST presenting as hemorrhagic cyst. A 63-year-old female with past medical history of hypertension and pancreatic mass presented with fatigue. She was found to have anemia requiring blood transfusion. An abdominal CT scan revealed an 11x16 cm cystic mass at the pancreatic body that had increased in size compared with previous CT scan. Endoscopic ultrasound confirmed a large complex pancreatic mass and fine needle aspiration demonstrated gross bloody fluid. Cytology revealed a spindle cell lesion. Immunohistochemistry from cyst wall biopsy was strongly positive for CD34 and CD117 confirming the diagnosis of pancreatic GIST. We report a case of pancreatic GIST which presented as hemorrhagic cyst. Endoscopic ultrasound guided fine needle aspiration plays an important role in the diagnosis. Although it is an uncommon tumor, pancreatic GIST should be in differential diagnosis of hemorrhagic pancreatic cystic lesions as well as a rare cause of solid pancreatic lesions.


FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve.
Fragile-X-Mental-Retardation-1- (FMR1)-gene is supposed to be a key gene for ovarian reserve and folliculogenesis. It contains in its 5'-UTR a triplet-base-repeat (CGG), that varies between 26 and 34 in general population. CGG-repeat-lengths with 55-200 repeats (pre-mutation = PM) show instable heredity with a tendency to increase and are associated with premature-ovarian-insufficiency or failure (POI/POF) in about 20%. FMR1-mRNA-expression in leucocytes and granulosa cells (GCs) increases with CGG-repeat-length in PM-carriers, but variable FMR1-expression profiles were also described in women with POI without PM-FMR1 repeat-length. Additionally, associations between low numbers of retrieved oocytes and elevated FMR1-expression levels have been shown in GCs of females with mid-range PM-CGG-repeats without POI. Effects of FMR1-repeat-lengths-deviations (n < 26 or n > 34) below the PM range (n < 55) on ovarian reserve and response to ovarian stimulation remain controversial. We enrolled 229 women undergoing controlled ovarian hyperstimulation for IVF/ICSI-treatment and devided them in three ovarian-response-subgroups: Poor responder (POR) after Bologna Criteria, polycystic ovary syndrome (PCO) after Rotterdam Criteria, or normal responder (NOR, control group). Subjects were subdivided into six genotypes according to their be-allelic CGG-repeat length. FMR1-CGG-repeat-length was determined using ALF-express-DNA-sequencer or ABI 3100/3130 × 1-sequencer. mRNA was extracted from GCs after follicular aspiration and quantitative FMR1-expression was determined using specific TaqMan-Assay and applying the ΔΔCT method. Kruskall-Wallis-Test or ANOVA were used for simple comparison between ovarian reserve (NOR, POR or PCO) and CGG-subgroups or cohort demographic data. All statistical analysis were performed with SPSS and statistical significance was set at p ≤ 0.05. A statistically significant increase in FMR1-mRNA-expression-levels was detected in GCs of PORs with heterozygous normal/low-CGG-repeat-length compared with other genotypes (p = 0.044). Female ovarian response may be negatively affected by low CGG-alleles during stimulation. In addition, due to a low-allele-effect, folliculogenesis may be impaired already prior to stimulation leading to diminished ovarian reserve and poor ovarian response. A better understanding of FMR1 expression-regulation in GCs may help to elucidate pathomechanisms of folliculogenesis disorders and to develop risk-adjusted treatments for IVF/ICSI-therapy. Herewith FMR1-genotyping potentially provides a better estimatation of treatment outcome and allows the optimal adaptation of stimulation protocols in future.


Voice and speech outcomes of chemoradiation for advanced head and neck cancer: a systematic review.
Purpose of this review is to systematically assess the effects on voice and speech of advanced head and neck cancer and its treatment by means of chemoradiotherapy (CRT). The databases Medline, Embase and Cochrane were searched (1991-2009) for terms head and neck cancer, chemoradiation, voice and speech rehabilitation. Twenty articles met the inclusion criteria, whereof 14 reported on voice outcomes and 10 on speech. Within the selected 20 studies, 18 different tools were used for speech or voice evaluation. Most studies assessed their data by means of patient questionnaires. Four studies presented outcome measures in more than one dimension. Most studies summarised the outcomes of posttreatment data that were assessed at various points in time after treatment. Except for four studies, pre-treatment measurements were lacking. This and the fact that most studies combined the outcomes of patients with radiated laryngeal cancers with outcome data of non-laryngeal cancer patients impedes an interpretation in terms of the effects of radiation versus the effects of the disease itself on voice or speech. Overall, the studies indicated that voice and speech degenerated during CRT, improved again 1-2 months after treatment and exceeded pre-treatment levels after 1 year or longer. However, voice and speech measures do not show normal values before or after treatment. Given the large-ranged posttreatment data, missing baseline assessment and the lacking separation of tumour/radiation sites, there is an urgent need for structured standardised multi-dimensional speech and voice assessment protocols in patients with advanced head and neck cancer treated with CRT.


[Adjacent rotated cutaneous flap to repair deep electrical burns at functional positions].
In this paper, five cases of electrical burns in 10 special areas were treated by adjacent rotated cutaneous flaps. The positions of injuries included 5 open joints injuries, 4 deep burns in heel region, 1 in perineum region. The results were satisfied except one case due to muscle necrosis and amputation was undertaken. This method is simple, effective, safe, reliable and suitable to repair injuries of any part of the body. It can shorten the course of disease and reduce the occurrence of complications.


Successful Fibrinolytic Therapy in a Challenging Obstructive Prosthetic Mitral Valve Thrombosis.
Prosthetic valve thrombosis is a rare and severe complication of the mechanical prosthetic valve. Management can be challenging due to varying clinical presentation, overlapping features of differential diagnosis, and lack of randomized controlled trials on the therapeutic options. In this article, we report the case of a patient with a mechanical prosthetic mitral valve presented with symptoms of heart failure, and an echocardiography showing increased mean pressure gradient across the prosthesis along with a fixed posterior leaflet and a partially restricted anterior leaflet with no visible mass. That raised the concern for an obstructed prosthesis. After multimodality imaging and multidisciplinary team discussions, prosthetic valve thrombosis diagnosis was favored over other different diagnoses that included but not limited to pannus ingrowth. Fibrinolytic therapy was administrated, and the patient was discharged on optimal anticoagulation. Repeated echocardiography a month later showed normal mean gradient and normal functioning prosthetic mitral valve without the need for repeat mitral valve surgery.


Physical and sedentary activity in adolescents with cerebral palsy.
Participation in regular physical activity (PA) provides health, psychological, and physiological benefits for people with and without a physical disability. This study investigated the physical and sedentary activity patterns of adolescents with cerebral palsy (CP). A cross-sectional, descriptive, postal survey was used, consisting of the Physical Activity Questionnaire for Adolescents (PAQ-A), self-reported level of gross motor function (based on the Gross Motor Function Classification System [GMFCS]), and specific questions regarding weekly sedentary activities. Following piloting to determine test-retest reliability (intraclass correlation [ICC] for PA=0.90; total weekly sedentary time=0.84) and concurrent validity (survey PA score vs pedometry, Pearson's r=0.24; survey PA score vs accelerometry, r=-0.21; survey weekly sedentary time vs logbook, r=0.38), the survey was mailed to all adolescents with CP in South Australia registered with Novita Children's Services (n=219). One hundred and twelve valid surveys were returned (76 males, 36 females; age range 11-17y, mean age 13y 11mo [SD 23mo]; GMFCS Level I, n=42; Level II, n=27; Level III, n=10; Level IV, n=17; Level V, n=15; level not reported, n=1). Results were compared with recent normative age- and sex-matched data sets. Key findings were that PA level of adolescents with CP was related to level of gross motor function and inversely related to age, and that adolescents with CP were less physically active than their peers without disability. Comparisons with normative data sets suggested that adolescents with CP tend to participate in less structured and lower intensity PA compared with non-disabled adolescents, though sedentary activity patterns (TV and computer use) of adolescents with and without CP were similar.


Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.
Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.


Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice.
Abnormal macrophages in MRL-lpr mice are implicated in the pathogenesis of autoimmune disease. These mice die of lupus nephritis by 5 to 6 months of age. This study reports that MRL-lpr mice have an increased level of circulating macrophage colony-stimulating factor (M-CSF) detectable as early as 1 week of age. Macrophage colony-stimulating factor decreased between 2 and 4 months and then steadily increased beginning at 4 months of age. In contrast, M-CSF was not detected in sera from congenic MRL-++ mice, normal C3H/FeJ mice, two other mouse strains with the lpr gene (B6-lpr and C3H-lpr), or another lupus model, the NZB/W mouse. These observations indicate that the lpr gene alone is not responsible for inducing this growth factor, and elevated M-CSF is not required for all forms of murine lupus. The entire source of serum M-CSF is not clear. The unique T cells regulated by the lpr gene are not responsible for the increased serum M-CSF levels, as no M-CSFs could be detected in supernatants from cultured lymph nodes from MRL-lpr mice, and the steady-state levels of M-CSF mRNA in lymph nodes and spleens in MRL-lpr, C3H-lpr mice and in their respective congenic strains were similar. The steady-state M-CSF mRNA transcripts in liver, lung, and bone marrow in MRL-lpr, MRL-++, and C3H/FeJ mice were also similar. Macrophage colony-stimulating factor transcripts were clearly elevated in the kidneys of MRL-lpr mice, suggesting a renal source of circulating M-CSF. The increase of M-CSF might be responsible for the increased numbers and enhanced functions of macrophages, which in turn cause tissue destruction in MRL-lpr mice.


Stable-isotope analysis of a deep-sea benthic-fish assemblage: evidence of an enriched benthic food web.
In this study, fishes and invertebrates collected from the continental slope (1000 m) of the eastern North Pacific Ocean were analysed using stable-isotope analysis (SIA). Resulting trophic positions (T(P) ) were compared to known diets and habitats from the literature. Dual isotope plots indicated that most species groups (invertebrates and fishes) sorted as expected along the carbon and nitrogen axes, with less intraspecific variability than interspecific variability. Results also indicated an isotopically distinct benthic and pelagic food web, as the benthic food web was more enriched in both nitrogen and carbon isotopes. Trophic positions from SIA supported this finding, resulting in the assignment of fishes to different trophic positions from those expected based on published dietary information. These differences can be explained largely by the habitat of the prey and the percentage of the diet that was scavenged. A mixing model estimated dietary contributions of prey similar to those of the known diet of Bathyraja trachura from stomach-content analysis (SCA). Linear regressions indicated that trophic positions calculated from SIA and SCA, when plotted against B. trachura total length for 32 individuals, exhibited similar variation and patterns. Only the T(P) from SCA yielded significant results (stomach content: P < 0·05, stable isotope: P > 0·05).


Bayesian Calibration of Microsimulation Models.
Microsimulation models that describe disease processes synthesize information from multiple sources and can be used to estimate the effects of screening and treatment on cancer incidence and mortality at a population level. These models are characterized by simulation of individual event histories for an idealized population of interest. Microsimulation models are complex and invariably include parameters that are not well informed by existing data. Therefore, a key component of model development is the choice of parameter values. Microsimulation model parameter values are selected to reproduce expected or known results though the process of model calibration. Calibration may be done by perturbing model parameters one at a time or by using a search algorithm. As an alternative, we propose a Bayesian method to calibrate microsimulation models that uses Markov chain Monte Carlo. We show that this approach converges to the target distribution and use a simulation study to demonstrate its finite-sample performance. Although computationally intensive, this approach has several advantages over previously proposed methods, including the use of statistical criteria to select parameter values, simultaneous calibration of multiple parameters to multiple data sources, incorporation of information via prior distributions, description of parameter identifiability, and the ability to obtain interval estimates of model parameters. We develop a microsimulation model for colorectal cancer and use our proposed method to calibrate model parameters. The microsimulation model provides a good fit to the calibration data. We find evidence that some parameters are identified primarily through prior distributions. Our results underscore the need to incorporate multiple sources of variability (i.e., due to calibration data, unknown parameters, and estimated parameters and predicted values) when calibrating and applying microsimulation models.


If we gave away mammograms, who would get them? A neighborhood evaluation of a no-cost breast cancer screening program.
Low- and no-cost mammography programs have become a widespread strategy to increase access to breast cancer screening in low-income populations. However, rigorous evaluations of who remains unscreened in communities with these programs are lacking. We conducted a case-control study of African American older women in East Baltimore, Maryland, comparing attendees at a no-cost program to friends and neighbors not using no-cost venues. We recruited 288 women ages 50 and older, who attended a no-cost program at Johns Hopkins Hospital, to complete a 1(1/2) h home interview, answering semistructured and open-ended questions about cancer and health and a wide range of social and psychological items. For each case, we recruited one friend or neighbor, within 5 years of age, not receiving no-cost screening, to complete a similar control interview. Matched case-control analyses were used to compare program attendees to nonattendees within the target community. Women using the no-cost program at least once were generally more poorly screened than their neighborhood control prior to the program, but had better recent screening history 3 years after the program began. In multivariate analyses, program attendees were more likely to have <10,000 dollars annual income (OR = 2.34, 95% CI 1.55,3.61), more likely to have had more children (OR = 1.13, 95% CI 1.04,1.24), and less likely to have health insurance (OR = 0.42, 95% CI 0.25,0.68). They were more likely to see a female primary care provider (OR = 1.82, 95% CI 1.24,2.70) and to see multiple providers (OR = 3.38, 95% CI 1.52,8.60). Low-cost screening intervention programs reach women who might otherwise not receive screening. However, within target communities, improved partnerships with specific types of primary care providers could reach additional women.


RIOK1 kinase activity is required for cell survival irrespective of MTAP status.
Genotype specific vulnerabilities of cancer cells constitute a promising strategy for the development of new therapeutics. Deletions of non-essential genes in tumors can generate unique vulnerabilities which could be exploited therapeutically. The MTAP gene is recurrently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene CDKN2A. Recent studies have uncovered an increased dependency of MTAP-deleted cancer cells on the function of a PRMT5 containing complex, including WDR77, PRMT5 and the kinase RIOK1. As RIOK1 kinase activity constitutes a potential therapeutic target, we wanted to test if MTAP deletion confers increased sensitivity to RIOK1 inhibition. Using CRISPR/Cas9-mediated genome engineering we generated analog sensitive alleles of RIOK1 in isogenic cell lines differing only by MTAP status. While we were able to independently confirm an increased dependency of MTAP-deleted cells on PRMT5, we did not detect a differential requirement for RIOK1 kinase activity between MTAP-proficient and deficient cells. Our results reveal that the kinase activity of RIOK1 is required for the survival of cancer cell lines irrespective of their MTAP status and cast doubt on the therapeutic exploitability of RIOK1 in the context of MTAP-deleted cancers.


Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells.
The high consumption of soy isoflavones in Asian diets has been correlated to a lower incidence of clinically important cases of prostate cancer. This study characterized the effects of a soy-derived isoflavone concentrate (ISF) on growth and gene expression profiles in the LNCaP, an androgen-sensitive human prostate cancer cell line. ISF caused a dose-dependent decrease in viability (P < 0.05) and DNA synthesis (P < 0.01), as well as an accumulation of cells in G(2)/M, and G(0)/G(1) phases of the cell cycle compared with controls. Using Affymetrix oligonucleotide DNA microarrays (U133A), we determined that ISF upregulated 80 genes and downregulated 33 genes (P < 0.05) involving androgen-regulated genes and pathways controlling cell cycle, metabolism, and intracellular trafficking. Changes in the expression of the genes of interest, identified by microarrays, were validated by Western immunoblot, Northern blot, and luciferase reporter assays. Prostate-specific antigen, homeobox protein NKX3, and cyclin B mRNA were significantly reduced, whereas mRNA was significantly upregulated for p21(CIP1), a major cell cycle inhibitory protein, and fatty acid and cholesterol synthesis pathway genes. ISF also significantly increased cyclin-dependent kinase inhibitor p27(KIP1) and FOXO3A/FKHRL1, a forkhead transcription factor. A differential pattern of androgen-regulated genes was apparent with genes involved in prostate cancer progression being downregulated by ISF, whereas metabolism genes were upregulated. In summary, we found that ISF inhibits the growth of LNCaP cells through the modulation of cell cycle progression and the differential expression of androgen-regulated genes. Thus, ISF treatment serves to identify new therapeutic targets designed to prevent proliferation of malignant prostate cells.


The promise of neuroprotective agents in Parkinson's disease.
Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.


Outcome of leptospirosis in children.
We conducted a retrospective analysis of 43 consecutive children (35 boys and 8 girls), 4-14 years of age and living in an urban area, who were hospitalized at the Instituto de Infectologia Emilio Ribas (Sao Paulo, Brazil) from January 1989 to December 1995 with an acute illness subsequently diagnosed as leptospirosis. Epidemiologic data indicated contact with contaminated water in most cases (88%). The patient sera reacted most strongly with Leptospira interrogans serovars copenhageni (45%) and icterohaemorrhagiae (32.7%). Jaundice was present in 70% of the patients, elevated transaminase levels in 56%, renal failure in 79%, meningitis in 23%, thrombocytopenia in 65%, and hemorrhagic manifestations in 11.6%. Three children had pulmonary hemorrhage with respiratory failure and one death occurred as a consequence of respiratory failure. We also observed that antimicrobial therapy reduced the extent of renal failure and thrombocytopenia. These data indicate that antibiotics benefit children with late, severe leptospirosis and that severe disease also occurs in children and should be considered in the differential diagnosis.


Statistical Copolymers that Mimic Aspects of Mussel Adhesive Proteins: Access to Robust Adhesive-Domains for Non-Covalent Surface PEGylation.
Reconstructing functional sequence motifs of proteins, using statistical copolymers greatly reduces the information content, but simplifies synthesis significantly. Key amino acid residues involved in the adhesion of mussel foot proteins are identified. The side-chain functionalities of Dopa, lysine, and arginine are abstracted and incorporated into acrylate monomers to allow controlled radical polymerization. The resulting Dopa-acrylate (Y*-acr), arginine-acrylate (R-acr), and lysine-acrylate (K-acr) monomers are polymerized in different monomer ratios and compositions by reversible addition fragmentation transfer polymerization with a poly(ethylene glycol) (PEG) macrochain transfer agent. This results in two sets of PEG-block-copolymers with statistical mixtures and different monomer ratios of catechol/primary amine and catechol/guanidine side-chain functionalities, both important pairs for mimicking π-cation interactions. The coating behavior of these PEG-block-copolymers is evaluated using quartz crystal microbalance with dissipation energy monitoring (QCM-D), leading to non-covalent PEGylation of the substrates with clear compositional optima in the coating stability and antifouling properties. The coatings prevent non-reversible albumin or serum adsorption, as well as reduce cellular adhesion and fungal spore attachment.


Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays.
The SARS-CoV-2 spike trimer is the primary antigen for several serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Until stable cell lines are developed to increase the titer of this secreted protein in mammalian cell culture, the low yield of spike protein produced from transient transfection of HEK293 cells will be a limiting factor for these assays. To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Through this investigation, we developed a simplified and robust purification strategy that consistently yields 5 mg of protein per liter of expression culture for two commonly used forms of the SARS-CoV-2 spike protein. We show that these proteins form well-behaved stable trimers and are consistently functional in serology assays across multiple protein production lots.


Nineteen-year trends in incidence and indications for laparoscopic cholecystectomy: the NY State experience.
Since the introduction of laparoscopic cholecystectomy (LC), there has been continued evolution in technique, instrumentation and postoperative management. With increased experience, LC has migrated to the outpatient setting. We asked whether increased availability and experience has impacted incidence of and indications for LC. The New York (NY) State Planning and Research Cooperative System longitudinal administrative database was utilized to identify patients who underwent cholecystectomy between 1995 and 2013. ICD-9 and CPT procedure codes were extracted corresponding to laparoscopic and open cholecystectomy and the associated primary diagnostic codes. Data were analyzed as relative change in incidence (normalized to 1000 LC patients) for respective diagnoses. From 1995 to 2013, 711,406 cholecystectomies were performed in NY State: 637,308 (89.58 %) laparoscopic. The overall frequency of cholecystectomy did not increase (1.23 % increase with a commensurate population increase of 6.32 %). Indications for LC during this time were: 72.81 % for calculous cholecystitis (n = 464,032), 4.88 % for biliary colic (n = 31,124), 8.98 % for acalculous cholecystitis (n = 57,205), 3.01 % for gallstone pancreatitis (n = 19,193), and 1.59 % for biliary dyskinesia (n = 10,110). The incidence of calculous cholecystitis declined (-20.09 %, p < 0.0001) between 1995 and 2013; meanwhile, other diagnoses increased in incidence: biliary colic (+54.96 %, p = 0.0013), acalculous cholecystitis (+94.24 %, p < 0.0001), gallstone pancreatitis (+107.48 %, p < 0.0001), and biliary dyskinesia (+331.74 %, p < 0.0001). Outpatient LC incidence catapulted to 48.59 % in 2013, from 0.15 % in 1995, increasing >320-fold. Analysis of LC through 2014 revealed increasing rates of digestive, infectious, respiratory, and renal complications, with overall cholecystectomy complication rates of 9.29 %. A shifting distribution of operative indications and increasing rates of complications should prompt careful consideration prior to surgery for benign biliary disease. For what is a common procedure, LC carries substantial risk of complications, thus requiring the patient to be an active participant and to share in the decision-making process.


Retrospective analysis of relative dose intensity in patients with non-Hodgkin lymphoma receiving CHOP-based chemotherapy and pegfilgrastim.
To evaluate primary prophylaxis with pegfilgrastim, a recombinant human granulocyte colony-stimulating factor, on maintaining relative dose intensity (RDI) in patients with non-Hodgkin lymphoma (NHL) receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-rituximab (CHOP-R). This retrospective analysis pooled data from pegfilgrastim NHL clinical trials. Patients received up to 6 cycles of CHOP/CHOP-R every 2 (Q2W) or 3 (Q3W) weeks. RDI and the patient incidence of dose delay, reduction, discontinuation, and adverse events leading to dose alteration/discontinuation were summarized overall and by age group (below 65, 65 to 75, and above 75 y) and treatment schedule. RDI during treatment exposure and RDI adjusted by the planned 6 cycles of treatment were calculated. The adjusted RDI was also evaluated with multiple regression analysis. Mean RDI during treatment exposure was 93% and 94% in overall patients in the Q2W and Q3W regimens, respectively. Mean adjusted RDI was 88% and 80%, respectively. The incidence of patients with RDI>85% was lower in older patients (65 y and above). In older patients, the incidence of dose reduction and discontinuation were higher regardless of treatment schedule, whereas dose delay was higher in the Q2W regimen. Multiple regression analysis identified age and cancer stage as potential factors associated with RDI. Adverse events leading to dose alteration/discontinuation were spread across hematological and nonhematological toxicities; older patients had a higher incidence of these adverse events. Pegfilgrastim primary prophylaxis maintained RDI in NHL patients receiving CHOP/CHOP-R during treatment. Adjusted RDI was lower in elderly patients because of early termination of chemotherapy.


The cis-regulatory codes of response to combined heat and drought stress in Arabidopsis thaliana.
Plants respond to their environment by dynamically modulating gene expression. A powerful approach for understanding how these responses are regulated is to integrate information about cis-regulatory elements (CREs) into models called cis-regulatory codes. Transcriptional response to combined stress is typically not the sum of the responses to the individual stresses. However, cis-regulatory codes underlying combined stress response have not been established. Here we modeled transcriptional response to single and combined heat and drought stress in Arabidopsis thaliana. We grouped genes by their pattern of response (independent, antagonistic and synergistic) and trained machine learning models to predict their response using putative CREs (pCREs) as features (median F-measure = 0.64). We then developed a deep learning approach to integrate additional omics information (sequence conservation, chromatin accessibility and histone modification) into our models, improving performance by 6.2%. While pCREs important for predicting independent and antagonistic responses tended to resemble binding motifs of transcription factors associated with heat and/or drought stress, important synergistic pCREs resembled binding motifs of transcription factors not known to be associated with stress. These findings demonstrate how in silico approaches can improve our understanding of the complex codes regulating response to combined stress and help us identify prime targets for future characterization.


Implementation and evaluation of a clinical data management programme in a primary care centre.
Electronic health records (EHR)support clinical management, administration, quality assurance, research, and service planning. The aim of this study was to evaluate a clinical data management programme to improve consistency, completeness and accuracy of EHR information in a large primary care centre with 10 General Practitioners (GPs). A Clinical Data Manager was appointed to implement a Data Management Strategy which involved coding consultations using ICPC-2 coding, tailored support and ongoing individualised feedback to clinicians. Over an eighteen month period there were improvements in engagement with and level of coding. Prior to implementation (August 2011) 4 of the 10 GPs engaged in regular coding and 69% of their consultation notes were coded. After 12 months, all 10 GPs and 6 nurses were ICPC-2 coding their consultations and monthly coding levels had increased to 98%. This structured Data Management Strategy provides a feasible sustainable way to improve information management in primary care.


Synchronization of cardiac-related discharges of sympathetic nerves with inputs from widely separated spinal segments.
We used phase spectral analysis to study the relationships between the cardiac-related discharges of pairs of postganglionic sympathetic nerves in urethan-anesthetized or decerebrate cats. Phase angle when converted to a time interval should equal the difference in conduction times from the brain to the nerves (i.e., transportation lag) if their cardiac-related discharges have a common central source. Transportation lag was estimated as the difference in the onset latencies of activation of the nerves by electrical stimulation of the medulla or cervical spinal cord. The phase angle for the cardiac-related discharges of two nerves was not always equivalent in time to the transportation lag. For example, in some cases the cardiac-related discharges of the renal nerve were coincident with or led those of the inferior cardiac nerve. In contrast, the electrically evoked responses of the renal nerve lagged those of the inferior cardiac nerve by > or = 32 ms. These observations are consistent with a model of multiple and dynamically coupled brain stem generators of the cardiac-related rhythm, each controlling a different sympathetic nerve or exerting nonuniform influences on different portions of the spinal sympathetic outflow.


Biochemical analysis and electron microscopic study on intracellular virions in NIH/3T3 mouse cells chronically infected with Moloney murine leukaemia virus: effect of interferon.
Radioactively labelled virus particles of intracellular origin were isolated from the cytoplasmic fraction of disrupted NIH/3T3 cells chronically infected with Moloney murine leukaemia virus [NIH/3T3 (MLV)]. Interferon (IFN) treatment for 48 h, which arrested more than 90% of virus release, resulted in a remarkable accumulation of these intracellular virions. However, no major effect of such treatment was apparent on their structural properties. Transmission electron microscopic examination revealed that these intracellular virions were located within cytoplasmic vacuoles. IFN treatment resulted in a considerable increase in the number of virus-containing vacuoles, as well as the total number of vacuolar virions. It seems that IFN inhibits the final release of vacuolar virions from the cells, thus leading to their intracellular accumulation.


Current status of cardiac glycoside drug interactions.
The effects of concomitant drug therapy on the absorption, distribution, and elimination of digoxin and digitoxin are reviewed. A number of agents can increase or decrease the absorption of digoxin and digitoxin from the gastrointestinal tract by altering GI motility, binding the drugs through physical adsorption, altering the properties of the intestinal wall, or altering the bacterial flora of the intestine. The steady-state serum concentrations of digoxin and digitoxin can be affected if the changes in absorption are of sufficient magnitude, and adjustments in digoxin or digitoxin dosage may be required. A reduction in digoxin and digitoxin protein binding has occurred during concomitant administration of heparin and cardiac glycosides. Since digitoxin is more highly protein bound than digoxin, interactions that involve changes in protein binding are of much greater clinical importance with digitoxin. A number of drugs increase or decrease the elimination of digoxin and digitoxin, and subtherapeutic or toxic concentrations of the cardiac glycosides often result. Drugs that induce hepatic microsomal enzymes can increase the elimination of digitoxin, which is eliminated mainly by hepatic biotransformation. Digoxin is eliminated mainly by renal excretion; renal clearance of digoxin may be increased by vasodilators and thyroid hormones and decreased by quinidine, verapamil, amiodarone, and potassium-sparing diuretics. The clinical importance of changes in serum concentrations of the cardiac glycosides that result from alterations in glycoside elimination requires further study, as does the importance of preliminary reports of interactions between cardiac glycosides and diazepam, captopril, and combination therapy with quinidine-pentobarbital or quinidine-rifampin. Because the cardiac glycosides have a narrow therapeutic range, patients receiving concomitant therapy with agents that might affect the absorption, distribution, or elimination of the cardiac glycosides should be monitored carefully for symptoms of digitalis toxicity or undertreatment.


A rare case of Actinomyces israelii presenting as pericarditis in a 75-year-old man.
Actinomyces israelii is a gram-positive bacillus that is rarely associated with infections in the general population. A. israelii belongs to the normal flora of the body and it rarely becomes pathogenic. Cardiac involvement is rare and in most cases involves the pericardium. Fewer than 20 cases of pericardial actinomycosis have been reported in the literature since 1950. We report the case of a 75-year-old man with a history of coronary artery disease with recent myocardial infarction and stent placement, atrial fibrillation, and recent colonic perforation with subsequent colectomy/colostomy who presented to our hospital with a 2-week history of left-sided chest pain. Workup revealed the presence of a pericardial effusion and pericarditis. Pericardial fluid analysis demonstrated A. israelii. An examination and discussion of the literature is performed regarding this rare manifestation of human actinomycosis.


The tissue source and cellular control of the apparent size of androgen binding protein (Abp), a mouse salivary protein whose electrophoretic mobility is under the control of sex-limited saliva pattern (Ssp).
Expression of the dominant allele, Ssps, at the Sex-limited saliva pattern locus in mice results in an alteration of the electrophoretic mobility of a mouse salivary protein from the F (fast) to the S (slow) type [Karn, R.C., et al. (1980). Genetics 94:s52; Karn, R.C., et al. (1982). Biochem. Genet. 20:493]. We now demonstrate that the protein affected binds androgen and has a basic heterodimeric structure with the subunits connected by disulfide bridging. It is produced in the submaxillary gland where the alteration takes place. The change in electrophoretic mobility from F to S appears to be primarily the result of an increase in the molecular weight of the larger subunit since the isoelectric point changes very little. We discuss the possible causes of the increase in molecular weight.


A Quantile Regression Approach to Understanding the Relations Among Morphological Awareness, Vocabulary, and Reading Comprehension in Adult Basic Education Students.
The purpose of this study was to investigate the joint and unique contributions of morphological awareness and vocabulary knowledge at five reading comprehension levels in adult basic education (ABE) students. We introduce the statistical technique of multiple quantile regression, which enabled us to assess the predictive utility of morphological awareness and vocabulary knowledge at multiple points (quantiles) along the continuous distribution of reading comprehension. To demonstrate the efficacy of our multiple quantile regression analysis, we compared and contrasted our results with a traditional multiple regression analytic approach. Our results indicated that morphological awareness and vocabulary knowledge accounted for a large portion of the variance (82%-95%) in reading comprehension skills across all quantiles. Morphological awareness exhibited the greatest unique predictive ability at lower levels of reading comprehension whereas vocabulary knowledge exhibited the greatest unique predictive ability at higher levels of reading comprehension. These results indicate the utility of using multiple quantile regression to assess trajectories of component skills across multiple levels of reading comprehension. The implications of our findings for ABE programs are discussed.


Sidewalk Landscape Structure and Thermal Conditions for Child and Adult Pedestrians.
Walking is being promoted for health and transportation purposes across all climatic regions in the US and beyond. Despite this, an uncomfortable microclimate condition along sidewalks is one of the major deterrents of walking, and more empirical research is needed to determine the risks of heat exposure to pedestrians while walking. This study examined the effect of street trees and grass along sidewalks on air temperatures. A series of thermal images were taken at the average heights of adults and children in the US to objectively measure the air temperatures of 10 sidewalk segments in College Station, TX, USA. After controlling the other key physical environmental conditions, sidewalks with more trees or wider grass buffer areas had lower air temperatures than those with less vegetation. Children were exposed to higher temperatures due to the greater exposure or proximity to the pavement surface, which tends to have higher radiant heat. Multivariate regression analysis suggested that the configuration of trees and grass buffers along the sidewalks helped to promote pleasant thermal conditions and reduced the differences in ambient air temperatures measured at child and adult heights. This study suggests that street trees and vegetated ground help reduce the air temperatures, leading to more thermally comfortable environments for both child and adult pedestrians in warm climates. The thermal implications of street landscape require further attention by researchers and policy makers that are interested in promoting outdoor walking.


Lens correction of astigmatism in a czerny-turner spectrograph.
This paper presents measurements of astigmatism for a typical Czerny-Turner spectrograph and shows two ways of correcting astigmatism in this instrument by using lenses. For an f/6.3 instrument having a 0.75-m focal length collimating and camera mirror, the meridional and sagittal focal planes were separated approximately 15 mm at 60 mm left of the center of the film plane and approximately 43 mm at 70 mm to the right of the center of the plane, when the grating was set to put 5000 A in the center of the film plane. Measurements of astigmatism for different lines of the Hg spectrum with 5000 A in the center of the film plane showed the astigmatism to be determined primarily, if not entirely, by the angle at which the radiation left the grating and collimating mirror. The experimental results compared favorably with the theory given by Rosendahl. Two methods of correcting astigmatism by lenses were investigated: one experimental, the other theoretical. Both appear to be practical.


Temperature sensitivity of decomposition decreases with increasing soil organic matter stability.
Evaluation of the temperature sensitivity of soil organic matter (SOM) decomposition is critical for forecasting whether soils in a warming world will lose or gain carbon and, therefore, accelerate or mitigate climate warming. It is usually described, using Arrhenius kinetics, as increasing with the stability of the substrate in laboratory conditions, where substrate availability is non-limiting and where chemical recalcitrance, therefore, predominantly regulates stability. However, conditions of non-limiting subtrate availability are rare in the undisturbed soil, where physicochemical protection of substrates may control their stability. The aim of this study was to assess the temperature sensitivity of decomposition of SOM with contrasting stability in the field. Our conceptual approach was based on in situ measurements of soil CO2 efflux at a range of temperatures from root exclusion plots of increasing age (1 month and three decades) and, therefore, with SOM of increasing stability. From a set of short-term measurements in spring, using diurnal temperature variation, the relative temperature sensitivity of SOM decomposition decreased significantly (p < 0.0001) with increasing SOM stability, and was weak (Q10 < 1.3) in long-term root exclusion plots. This result was confirmed in a similar set of short-term measurements repeated later in the year, in summer, as well as from an analysis perfomed at the seasonal timscale. We provide direct field evidence that the temperature sensitivity of SOM decomposition decreases with increasing stability, in direct contrast with Arrhenius kinetics prediction, and therefore show that stability of SOM in the field cannot be the sole result of chemical recalcitrance. We conclude that the physicochemical protection of SOM, which controls SOM stability in the field, constrains the temperature sensitivity of SOM decomposition under field conditions.


The influence of hydrazine, phenelzine and nialamide on gluconeogenesis and cell respiration in the perfused guinea-pig liver.
Hydrazine (2 mmol/l) and phenelzine (0.5 mmol/l), which are known to produce hypoglycaemia, inhibit glucose formation from lactate in the perfused guinea-pig liver. The hydrazone formed from pyruvate and phenelzine exerted the same effect at concentrations of only 0.05 mmol/l. It is suggested that the hydrazones are the substances which are effective. All these compounds inhibited pyruvate consumption and decreased CO2 production by the perfused liver which, togeteher with the pattern of hepatic metabolite concentrations, indicate that they diminish pyruvate metabolism. None of them influenced the activities in vitro of pyruvate carboxylase, phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase. The hydrazone compound caused an increase of the ATP/ADP ration at lower concentrations and an opposite effect above 0.5 mmol/l. Nialamide, another hydrazine derivative, also reduced hepatic glucoeogenesis but led to a marked decrease in the hepatic ATP/ADP ratio and liver cell respiration accompanied by a rise in the 3-hydroxybutyrate/acetoacetate ratio.


ICU-acquired weakness.
Observational studies of patients receiving prolonged mechanical ventilation and other forms of critical care support have determined acquired neuromuscular disorders to be extremely common. Early studies used electrophysiologic investigations to diagnose critical illness polyneuropathy (CIP) and muscle biopsy to confirm critical illness myopathy (CIM). More recent approaches seek to obviate these invasive techniques and build on a standardized bedside neuromuscular examination to identify patients with acquired weakness syndromes. Serial examination in the alert patient may serve as a reasonable prognosticator for most patients. The importance of ICU-acquired weakness syndromes is supported by the observation that muscle wasting and weakness are among the most prominent long-term complications of survivors of ARDS. In addition, a strong association appears to exist between acquired weakness and protracted ventilator dependence, an important determinant of ICU length of stay. Multivariate analysis has identified several risk factors associated with increased incidence for ICU-acquired weakness, including severe systemic inflammation, medications (specifically, corticosteroids and neuromuscular blocking agents), glycemic control, and immobility. We advocate an approach to this common syndrome that identifies risk factors early in the hope of minimizing their impact.