Characterization and chromosomal mapping of a cDNA encoding tryptophan hydroxylase from a mouse mastocytoma cell line.
A cDNA library was constructed from RNA prepared from P815 mouse mastocytoma cells and screened for tryptophan hydroxylase. An essentially full-length clone that recognizes a major mRNA species of 1.9 kb in mastocytoma cell lines and in pineal gland, duodenum, and brainstem of the mouse was obtained. The predicted amino acid sequence of this mouse mastocytoma clone showed 97 and 87% identity, respectively, with tryptophan hydroxylase clones isolated from rat and rabbit pineal glands, but the mouse clone contains an unusual 3-amino-acid duplication near the N-terminus and lacks a phosphorylation site. A fragment of the cDNA produced an enzymatically active protein when expressed in Escherichia coli, thus demonstrating that the catalytic domain is included in the C-terminal 380 amino acids. The mouse tryptophan hydroxylase locus, termed Tph, was mapped by Southern blot analysis of somatic cell hybrids and by an interspecific backcross to a position in the proximal half of chromosome 7. Because TPH has been mapped to human chromosome 11, this assignment further defines regions of homology between these mouse and human chromosomes.


Effect of serum type and concentration on the expression ofβ-galactosidase in recombinant vaccinia virus infected HeLa S3 cells.
The effect of serum type and concentration on recombinant protein expression in vaccinia virus infected HeLa S3 cells was studied in both static and suspension culture. A model heterologous protein,β-galactosidase (β-gal), was used. Calf and horse sera in the range of 0.5-10%(v/v) were investigated. In static culture, the calf serum concentration did not show any significant influence on the β-gal production which was almost completed within 24h postinfection (pi). Higher horse serum concentration, on the other hand, resulted in higher β-gal concentration which continued to increase until 48 h pi. Total β-gal concentrations in 0.5% calf serum at 24 h pi and 10% horse serum at 48 h pi were 2.2±0.7 and 2.2±0.1 IU/ml, respectively. In suspension culture, both sera showed their respective effects on the β-gal production similar to those observed in static culture, indicating that the cultivation method had little influence on β-gal production. Accordingly, the use of 0.5% calf serum after virus infection in recommended for economical β-gal production.


Intraparotid facial nerve schwannoma: a 17-year, single-institution experience of diagnosis and management.
Intraparotid facial nerve schwannoma (IFNS) is rare and its definite preoperative diagnosis is challenging. To improve available knowledge regarding the diagnosis of IFNS and to suggest an appropriate treatment plan. We retrospectively analyzed medical records of IFNS patients at our hospital. Inclusion criteria were surgery (from January 2000, to December 2016) for a parotid mass, pathologically diagnosed as a schwannoma. The study included 42 eligible patients who had undergone tumor resection from 5977 parotid tumor patients. Mostly presented hard-textured (18/39) or medium-textured (15/39), with limited mobility (21/39) mass (three tumors were not palpable). Their facial nerve function outcomes were House-Brackmann Grade I (n = 14), Grade II (n = 7), Grade III (n = 11), Grade IV (n = 5), Grade V (n = 3), and Grade VI (n = 2). Significant differences were noted in results based on different surgical methods used (p = .000) and tumor involvement (p = .002). A hard-textured tumor with limited mobility mass in the parotid gland should prompt the diagnosis of a schwannoma. Tumors involving main trunk usually lead to unsatisfactory facial nerve outcomes. Facial nerve preservation should always be essential, and stripping surgery or intracapsular enucleation could be the preferred surgical methods of choice.


Revisiting the Utility of Granulocyte Colony-Stimulating Factor Post-Autologous Hematopoietic Stem Cell Transplantation for Outpatient-Based Transplantations.
The use of granulocyte colony-stimulating factor (G-CSF) after autologous stem cell transplantation (ASCT) has been shown to reduce the time to neutrophil engraftment, as well as the duration of hospitalization post-transplantation. However, prior studies have focused on inpatient-based ASCT, where patients are routinely admitted for conditioning and frequently remain hospitalized until signs of neutrophil recovery. Given improvements in post-transplantation care, an increasing number of patients, particularly those receiving ASCT for multiple myeloma, are now undergoing transplantation in an outpatient setting. We hypothesized that the routine use of G-CSF for outpatient-based ASCT might not result in the same benefit with respect to a reduced duration of hospitalization and thus should be reconsidered in this setting. We performed a retrospective cohort study of 633 consecutive patients with multiple myeloma (MM; n = 484) or non-Hodgkin lymphoma (NHL; n = 149) who underwent ASCT between September 2018 and February 2023. Outpatient ASCT comprised 258 (53%) of combined MM and NHL cases. Starting in September 2021, post-transplantation G-CSF was incorporated into the supportive care regimen for all ASCTs. A total of 410 patients (309 with MM, 101 with NHL) underwent ASCT during the pre-G-CSF policy period and 223 (175 with MM, 48 with NHL) did so in the post-G-CSF policy period. The primary outcome focused on the duration of hospitalization within the first 30 days following graft infusion. As expected, after implementation of the G-CSF policy, the time to neutrophil engraftment was reduced in the patients with MM (mean, -2.8 days; P < .0001) and patients with NHL (mean, -2.9 days; P < .0001). However, among the patients with MM, roughly one-half of whom underwent outpatient-based ASCT, the inpatient duration during the first 30 days was not reduced after G-CSF implementation (P = .40). Comparatively, the inpatient duration (mean, -1.8 days; P = .030) was reduced among patients with NHL, all of whom were electively admitted for ASCT. For patients with MM at an outpatient-based transplant center, incorporation of G-CSF post-ASCT resulted in reduced time to neutrophil engraftment but did not significantly reduce the time spent in the inpatient setting through day +30.


Segmental motion at the peak of the ossification foci is independent risk factor except for mal-alignment and thick ossification foci for poor outcome after laminoplasty for cervical ossification of the posterior longitudinal ligament: analyses in patients with positive K-line, lordotic alignment, and lower canal occupying ratio.
To elucidate the independent preoperative factors that have a significant impact on poor surgical outcome after laminoplasty for K-line (+) ossification of the posterior longitudinal ligament (OPLL). Analyses in K-line (+) patient population can exclude the influence by mal-alignment and thick OPLL, both of which are well known two major factors that have significant impact on clinical outcome. The present study included 72 patients (50 male and 22 female) who underwent laminoplasty for K-line (+) cervical OPLL and were followed-up for at least 1 year. Recovery of Japanese Orthopedic Association score (JOA score) for cervical myelopathy was used as the measure of clinical outcome. For radiographic assessment, the type of OPLL, the maximum OPLL occupation ratio, the C2-C7 angle, and the segmental range of motion at the peak of OPLL (segmental ROM) were assessed. To elucidate the factors that are significantly associated with a poor clinical outcome after laminoplasty for K-line (+) OPLL, statistical analyses were conducted. The mean preoperative JOA score was 8.9 points and improved to 12.8 points after surgery. The recovery of JOA score was 47 ± 35%. Stepwise logistic regression following univariate analyses revealed that preoperative segmental ROM at the peak of OPLL is an independent factor associated with a poor outcome (p = 0.04, odds ratio = 1.15). Large preoperative segmental ROM at the peak of the OPLL is an independent factor that has significant impact on poor surgical outcome after laminoplasty for K-line (+) OPLL.


The clinical significance of food-induced changes in the absorption of theophylline from Uniphyl tablets.
To determine the effects of food on the absorption of theophylline from Uniphyl tablets (a once-daily sustained-release theophylline formulation), we performed a crossover evaluation in 20 adults with asthma. After 5 days of continuous dosing (at 6 PM), all patients received their regular Uniphyl dose under specified fasting conditions, and serum theophylline concentrations were measured sequentially during the following 24 hours. The patients' next Uniphyl dose was administered immediately after ingestion of a standardized high-fat meal, and theophylline concentrations were again measured during 24 hours. Five days later, the procedure was repeated in the opposite order. The patients' mean daily theophylline dose was 890.0 +/- 229.2 mg. We found relatively minor, but in some cases statistically significant, differences in pharmacokinetic parameters between food and fasting administration. When Uniphyl was administered with food, bioavailability was increased by 10% (p less than 0.01), the time of maximum concentration occurred 3 hours later (p less than 0.01), and the minimum or "trough" theophylline concentration was 0.7 mg/L greater (p less than 0.01), as compared to administration while patients were fasting. There was no evidence of "dose dumping" after either food or fasting administration of Uniphyl, and there was no significant difference in the maximum theophylline concentration attained between the two dosing conditions. There was no evidence of a difference in therapeutic efficacy between the two dosing conditions. All patients tolerated the drug well throughout the trial.


Alternative lactose catabolic pathway in Lactococcus lactis IL1403.
In this study, we present a glimpse of the diversity of Lactococcus lactis subsp. lactis IL1403 beta-galactosidase phenotype-negative mutants isolated by negative selection on solid media containing cellobiose or lactose and X-Gal (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside), and we identify several genes essential for lactose assimilation. Among these are ccpA (encoding catabolite control protein A), bglS (encoding phospho-beta-glucosidase), and several genes from the Leloir pathway gene cluster encoding proteins presumably essential for lactose metabolism. The functions of these genes were demonstrated by their disruption and testing of the growth of resultant mutants in lactose-containing media. By examining the ccpA and bglS mutants for phospho-beta-galactosidase activity, we showed that expression of bglS is not under strong control of CcpA. Moreover, this analysis revealed that although BglS is homologous to a putative phospho-beta-glucosidase, it also exhibits phospho-beta-galactosidase activity and is the major enzyme in L. lactis IL1403 involved in lactose hydrolysis.


Impact of Mandatory Infectious Disease Specialist Approval on Hospital-Onset Clostridioides difficile Infection Rates and Testing Appropriateness.
Inappropriate Clostridioides difficile testing is common in the hospital setting, leading to potential overdiagnosis of infection when single-step nucleic acid amplification testing is used. The potential role of infectious diseases (ID) specialists in enforcing appropriate C. difficile testing is unclear. At a single 697-bed academic hospital, we performed a retrospective study from 1 March 2012 to 31 December 2019 comparing hospital-onset C. difficile infection (HO-CDI) rates during 3 consecutive time periods: baseline 1 (37 months, no decision support), baseline 2 (32 months, computer decision support), and intervention period (25 months, mandatory ID specialist approval for all C. difficile testing on hospital day 4 or later). We used a discontinuous growth model to assess the impact of the intervention on HO-CDI rates. During the study period, we evaluated C. difficile infections across 331 180 admission and 1 172 015 patient-days. During the intervention period, a median of 1 HO-CDI test approval request per day (range, 0-6 alerts/day) was observed; adherence by providers with obtaining approval was 85%. The HO-CDI rate was 10.2, 10.4, and 4.3 events per 10 000 patient-days for each consecutive time period, respectively. In adjusted analysis, the HO-CDI rate did not differ significantly between the 2 baseline periods (P = .14) but did differ between the baseline 2 period and intervention period (P < .001). An ID-led C. difficile testing approval process was feasible and was associated with a >50% decrease in HO-CDI rates, due to enforcement of appropriate testing.


Computerized stripping method for multiple nuclide microsphere studies.
Radiolabeled microspheres are commonly used to measure cardiac output and regional blood flow distribution in small animals such as rats. By using batches of microspheres labeled with different nuclides, several flow measurements can be made in the same animal. A protocol and computer program for analyzing data from multiple nuclide microsphere experiments are described. This protocol is designed to reduce the amount of arterial blood which must be withdrawn during microsphere distribution and eliminate the potential loss of data due to contamination of reference samples by nuclides used in previous flow measurements.


Investigation into the reasons for preventable drug related admissions to a medical admissions unit: observational study.
To describe the drugs and types of medicine management problems most frequently associated with preventable drug related admissions to an acute medical admissions unit. Observation study. Medical admissions unit in a teaching hospital in Nottingham, UK. 4093 patients seen by pharmacists on the medical admissions unit between 1 January and 30 June 2001. Proportion of admissions that were drug related and preventable, classification of the underlying causes of preventable drug related admissions, and identification of drugs most commonly associated with preventable drug related admissions. Of the admissions seen by pharmacists, 265 (6.5%) were judged to be drug related and 178 (67%) of these were judged to be preventable. Preventable admissions were mainly due to problems with prescribing (63 cases (35%)), monitoring (46 cases (26%)), and adherence to medication (53 cases (30%)). The drugs most commonly implicated were NSAIDs, antiplatelets, antiepileptics, hypoglycaemics, diuretics, inhaled corticosteroids, cardiac glycosides, and beta-blockers. Potentially preventable drug related morbidity was associated with 4.3% of admissions to a medical admissions unit. In 91% of cases these admissions were related to problems with either prescribing, monitoring, or adherence.


Analysis of protein-surfactant interactions--a titration calorimetric and fluorescence spectroscopic investigation of interactions between Humicola insolens cutinase and an anionic surfactant.
We have studied interactions of cutinase (HiC) from Humicula insolens and sodium dodecyl sulphate (SDS) by parallel calorimetric and fluorescence investigations of systems in which the concentration of both components was changed systematically. Results from the two methods exhibit a number of synchronous characteristics, when plotted against the total SDS concentration, [SDS]tot. The molecular origin of several of these anomalies was assigned, and five intervals of [SDS]tot in which different modes of interactions dominated were identified. Going from low to high [SDS]tot, these modes were: binding of (a few) SDS to native HiC, formation of oligomeric protein aggregates, denaturation of HiC and adsorption of SDS on denatured protein. For [SDS]tot>3-6 mM (depending on the protein concentration), the adsorption saturated, and no further protein-detergent interaction could be detected. Two particularly conspicuous anomalies in the calorimetric data were ascribed to respectively denaturation and saturation. It was found that [SDS]tot at these points depended linearly on the (total) protein concentration, [HiC]. We suggest that this reflects the balance between bound and free SDS [SDS]tot=[SDS]aq+[HiC] Nb where [SDS]aq and Nb are, respectively, the aqueous ("free") concentration of SDS and the average number of SDS bound per protein. Interpretation of the results along these lines showed that at 22 degrees C and pH 7.0, HiC denatures with approximately 14 bound surfactant molecules at [SDS]aq=1.0 mM. Saturation is characterized by Nb approximately 39 and [SDS]aq=2.2 mM. The latter value is equal to CMC in the (protein free) buffer. These results are discussed with respect to the SDS-binding capacity of HiC and the origin and location of the saturation point.


Repopulating potential of canine bone marrow cells: differences between large and small cells separated by velocity sedimentation.
This study compares the pattern of haemopoietic recovery in dogs after total-body irradiation and transfusion of different populations of cryopreserved autologous bone marrow cells. Dogs in group 1 received unseparated marrow cells. Group-II dogs were transfused with small (less than 5.1 mm/h) and group-III dogs with large (greater than 7.1 mm/h) bone marrow cells, separated by velocity sedimentation. Myeloid progenitor cells (CFU-GM) present in slowly sedimenting cell fractions were characterized by a higher radiosensitivity in vitro and a lower proportion of cells in S-phase as compared to rapidly sedimenting CFU-GM. Although autografts in all groups contained comparable numbers of CFU-GM, transfusions resulted in different patterns of recovery. Fractions of small bone marrow cells contained most of the pluripotent stem cells, leading to speedy haematological reconstitution and long-term survival. The pattern of early recovery was similar in dogs of group I and of group II. In group III, the recovery in all cell lineages was delayed, going along with marked extramedullary haemopoiesis. The data may indicate the limits of committed progenitors in reflecting pluripotential stem cells, in particular, if bone marrow grafts have been modified in vitro. Differences in the repopulating potential of the graft might be reflected by distinct physical and biological properties of the CFU-GM.


High-Cost Users of Prescription Drugs: National Health Insurance Data from South Korea.
In OECD countries, pharmaceutical spending reached around 800 billion USD in 2013, accounting for about 20% of total spending in the retail sector. Pharmaceutical expenditures are steadily increasing in South Korea, necessitating strategies to promote efficiency. This study investigated factors associated with high-cost users (HCUs), who account for the majority of outpatient prescriptions in the total South Korean population. The top 20 frequently prescribed therapeutic subgroups were also investigated. This is an observational study performed using health insurance claims data in 2019. In total, 44,744,632 people (including 6,806,339 aged 65 years or older) who were prescribed outpatient medications were included. HCUs were defined as those for whom prescription drug costs were in the top 5%. Multivariate logistic regression analysis was performed using factors including age, insurance type, number of prescription drugs, outpatient visit days, prescription treatment days, and chronic diseases. HCUs accounted for 3.6 million (5% of the total population) and 1.4 million (21.1% of those 65 years or older). Furthermore, 4.1% of HCUs in the total population had few comorbidities. Male sex, older age, insurance (Medical Aid), comorbidities, chronic diseases, number of prescription drugs, outpatient visit days, and prescription days were all associated with an increased probability of being an HCU. The highest spending was found for B01 (antithrombotic agents) with 0.4 billion USD, followed by C10 (lipid-modifying agents) and A10 (drugs used in diabetes). The proportion of spending for HCUs among the general population was highest in L01 (antineoplastic agents), at 98.2%, and L04 (immunosuppressants), at 87.8%, whereas among the elderly, the highest proportions were found for B01 (antithrombotic agents), at 44.5%, and N06 (antidepressants), at 44.3%. Age and multiple chronic conditions were strongly associated with HCUs, and it seems necessary to reduce drug prescriptions in patients without complex comorbidities. Several measures should target those without multiple chronic conditions who are nonetheless HCUs.


Production of procedural discourse in aphasia.
The abilities of a group of 15 moderately impaired aphasics and 15 normals to produce procedural discourse are described. The experimental tasks included producing four procedures of varying levels of complexity. The data were analyzed in terms of sentential grammar, discourse grammar, and subjective ratings of content and clarity of language. The results showed that aphasics produced well-structured discourse. The language of the aphasics' discourse was reduced in both complexity and amount, but was not qualitatively different from the language produced by the normals. The reduction of language in the procedures reflected selective reduction of hierarchically organized information. The investigation suggests that aphasics are capable of manipulating different types of information and that they might be helped in this by utilizing instrumental scripts which are representation of knowledge underlying procedures.


MR properties of excised neural tissue following experimentally induced inflammation.
Changes in the MR parameters of inflamed neural tissue were measured in vitro. Tumor necrosis factor-alpha (TNF-alpha) was injected into rat sciatic nerves to induce inflammation with negligible axonal loss and demyelination. The MR parameters, such as T1/T2 relaxation and magnetization transfer (MT), were measured 2 days after TNF-alpha injection and were found to be substantially different from those of normal nerves. The average T1/T2 relaxation times increased, whereas the MT ratio (MTR) and the quantitative MT parameter M0B (which describes the semisolid pool of protons) decreased. The MR parameters correlated very well with the extracellular volume fraction (EM) of neural tissue evaluated by quantitative histopathology. The multicomponent T2 relaxation was shown to provide the best quantitative assessment of changes in neural tissue microstructure, and allowed us to distinguish between the processes of inflammation and demyelination. In comparison, the MT measurements were less successful due to competing contributions of demyelination and pH-sensitive changes in the MT effect.


Comparison of anticoagulant effects on vein grafts between human TFPI gene transfection and aspirin oral administration.
To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.


Traditional uses of Salvia libanotica (East Mediterranean sage) and the effects of its essential oils.
The extract of sage (Salvia libanotica), a plant endemic to the Mediterranean region, is the most popular plant remedy used by the Middle Eastern people to treat common complaints such as colds and abdominal pain. This review paper describes the East Mediterranean sage plant, Salvia libanotica, its geographic distribution, essential oil components, and popular uses in traditional medicine. The paper also discusses the therapeutic value of the individual components present in the essential oil extract of this plant, and the complications that could arise from the irrational use of this extract by man.


Long-term effect of full-mouth tooth extraction on the responsiveness of peripheral blood monocytes.
As some residual inflammation may remain after periodontal therapy, the present pilot study investigated the long-term effect of full-mouth tooth extraction therapy on the responsiveness of peripheral blood monocytes in a case with generalized terminal adult periodontitis. Before and 3, 9, 20 and 32 months after therapy, venous blood was collected. Total and differential white blood cell counts were determined and whole blood cell cultures (WBCC) were incubated with lipopolysaccharide (LPS) to stimulate the production of inflammatory mediators by monocytes. After full-mouth tooth extraction, the numbers of total peripheral white blood cells and neutrophils decreased over time. The release of the chemokines interleukin (IL)-8 and macrophage chemoattractant protein (MCP)-1 in the cultures decreased twofold over time, whereas no changes were seen for the other studied cytokines, chemokines and prostaglandin E2. On the basis of previous studies and the present case, the high production of IL-8 and MCP-1 by monocytes in LPS-stimulated WBCC from periodontitis patients is most likely acquired, as their levels decrease over time when the periodontal infection is controlled. The possible connection between periodontitis and atherosclerosis through IL-8 and MCP-1 is discussed.


Chromosome aberrations and cytogenetic intratumor heterogeneity in chondrosarcomas.
Clonal chromosome aberrations identified after short-term culture are presented for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9 tumors. The most frequent numerical anomalies were, in falling order of frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and 20. No recurrent structural rearrangement was found, but chromosome bands 5q13, 1q21, 7p11, and 20q11 were each involved in three different rearrangements. Karyotypic heterogeneity was assessed in two different ways: as the presence of more than one clone in one sample and as the presence of different clones in different samples from the same surgical specimen. Clonal karyotypic evolution was demonstrated in 6 of the 7 cases in which two or more samples could be investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity was found in only 5 of the 28 samples with aberrations. By comparing the incidences of the nonrandomly occurring aberrations in stemlines and sidelines in the heterogeneous tumors, it was possible to conclude that loss of chromosome 13 and rearrangement of band 5q13 were early events in the clonal evolution.


Aurora kinase A regulates liver regeneration through macrophages polarization and Wnt/β-catenin signalling.
Liver regeneration is a complex process regulated by a variety of cells, cytokines and biological pathways. Aurora kinase A (AURKA) is a serine/threonine kinase that plays a role in centrosome maturation and spindle formation during the cell division cycle. The purpose of this study was to further explore the mechanism of AURKA on liver regeneration and to identify new possible targets for liver regeneration. The effect and mechanism of AURKA on liver regeneration were studied using a 70% hepatectomy model. Human liver organoids were used as an in vitro model to investigate the effect of AURKA on hepatocyte proliferation. AURKA inhibition significantly reduced the level of β-catenin protein by reducing the phosphorylation level of glycogen synthase kinase-3β (GSK-3β), leading to the inhibition of liver regeneration. Further studies showed that AURKA co-localized and interacted with GSK-3β in the cytoplasm of hepatocytes. When phosphorylation of GSK-3β was enhanced, the total GSK-3β level remained unchanged, while AURKA was not affected, and β-catenin protein levels were increased. In addition, AURKA inhibition affected the formation and proliferation of human liver organoids. Furthermore, AURKA inhibition led to the polarization of M1 macrophages and the release of interleukin-6 and Tumour necrosis factor α, which also led to reduced liver regeneration and increased liver injury. These results provide more details on the mechanism of liver regeneration and suggest that AURKA is an important regulator of this mechanism.


Fatal left internal mammary artery graft to subclavian vein fistula complicating dual-chamber pacemaker implantation.
We describe the case of a 75-year-old woman with an iatrogenic fistula between a left internal mammary artery graft to the left anterior descending coronary artery and the left subclavian vein that developed after implantation of a dual-chamber pacemaker.


Changes in muscularis externa of rat small intestine after myenteric ablation with benzalkonium chloride: electron microscopic and morphometric study.
The influence of the intrinsic innervation on the muscularis externa of the rat small intestine was studied by chemical ablation of the myenteric plexus with benzalkonium chloride (BAC). The resulting severe hypertrophy (cell hypertrophy of 96-133% and hyperplasia) differs from working hypertrophy by the distribution and degree of muscle thickening and by characteristics of the extracellular matrix: narrowing of muscle interspaces of 43%; lack of increased collagen; changes in the ratio of interstitial cells of Cajal (ICCs) to fibroblasts from 1.6:1 to 0.8:1 with no numerical decrease in either type of cell; decreased interconnections of ICCs to muscles and nerves due to deformed ICCs; a 197% increase in vascularization (capillaries, venules) and lymphatics in both muscle layers and in the myenteric plexus cleft, possibly initiated by release of fibroblast growth factor from myelin fragmentation after nerve damage; and increased macrophages, plasma cells, monocytes and mast cells in the myenteric plexus cleft. These all signify the neural influence on the morphodifferentiation of the muscularis externa in concert with the extracellular matrix components.


The long non-coding RNA CCAT2 is up-regulated in ovarian cancer and associated with poor prognosis.
Ovarian cancer is a malignant tumor with a poor prognosis. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are emerging regulators in cancer biology, and can be used as potential biomarkers for cancer diagnosis, prognosis and targeted therapy. The lncRNA CCAT2 (colon cancer associated transcript 2) was recently shown to be involved in several cancers; however, its role in ovarian cancer remains unknown. Expression levels of the lncRNA CCAT2 in ovarian cancer tissues, adjacent normal tissues, and cell lines were assessed by quantitative real-time PCR. Then, the associations of CCAT2 expression levels with clinicopathological features and prognosis were evaluated. In addition, CCAT2 functions in tumor progression and invasion were further determined by siRNA-induced CCAT2 silencing in vitro. Expression levels of the lncRNA CCAT2 in ovarian cancer tissues and cell lines were significantly higher compared with values obtained for adjacent non-tumor tissues and normal ovarian epithelial cells. Interestingly, higher CCAT2 expression levels were associated with a shorter overall survival (P = 0.006) and disease-free survival (P = 0.001) in ovarian cancer patients. In addition, CCAT2 expression was positively correlated with FIGO stage (P = 0.002), tumor grade (P = 0.006) and distant metastasis (P < 0.001). Moreover, CCAT2 knockdown in ovarian cancer cells markedly suppressed cell proliferation, migration, and invasion. The lncRNA CCAT2 is a novel factor involved in ovarian cancer progression, and constitutes a potential prognostic biomarker and therapeutic target for patients with ovarian cancer.


Analysis of Network Pharmacology and Molecular Docking on Radix Pseudostellariae for Its Active Components on Gastric Cancer.
Radix Pseudostellariae, a traditional Chinese medicine, functions in modulating human immunity and anti-tumor, but its pharmacological mechanism remained unclear. In this study, 8 active components and 91 targets of Radix Pseudostellariae were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and 225 genes related to gastric cancer (GC) were accessed from MalaCards. On the basis of these targets and GC-related genes, a protein-protein interaction (PPI) network was established. Random walk with restart (RWR) analysis was performed on the PPI network with the intersection of targets and GC-related genes as the seeds. The top 50 target genes with high affinity scores were obtained. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the enrichment of the top 50 genes was mostly presented in the cancer-related biological functions and signaling pathways, such as cellular response to oxidative stress, regulation of apoptotic signaling pathway, and P53 signaling pathway. A drug-component-target network was established, with the top 50 genes being used as key targets. Acacetin and luteolin were revealed to directly act on the core target TP53 in the network. Thus, SwissDock was used to simulate the molecular docking between TP53 protein and acacetin and luteolin. The results of docking simulation presented small estimated ΔG of two small molecules, which were suggested to be potential targets of TP53 protein. Subsequent cellular and molecular experiments confirmed this bioinformatics result. In conclusion, this study predicted the key anti-GC active components and corresponding targets of Radix Pseudostellariae through bioinformatics analysis. The findings underlie the anti-GC mechanism of Radix Pseudostellariae.


Microglial neurotransmitter receptors trigger superoxide production in microglia; consequences for microglial-neuronal interactions.
Microglia express three isoforms of the NADPH oxidase, Nox1, Nox2 and Nox4, with the potential to produce superoxide (O(2) ˙(-) ). Microglia also express neurotransmitter receptors, which can modulate microglial responses. In this study, microglial activity of Nox1, Nox2 and Nox4 in primary rat cultured microglia or the rodent BV2 cell line were altered by microglial neurotransmitter receptor modulation. Glutamate, GABA or ATP triggered microglial O(2) ˙(-) production via Nox activation. Nox activation was elicited by agonists of metabotropic mGlu3 receptors and by group III receptors, by GABA(A) but not GABA(B) receptors, and by purinergic P2X(7) or P2Y(2/4) receptors but not P2Y(1) receptors, and inhibited by metabotropic glutamate receptor 5 antagonists. The neurotransmitters also modulated Nox mRNA expression and NADPH activity. The activation of Nox by BzATP or GABA promoted a neuroprotective phenotype whilst the activation of Nox by glutamate promoted a neurotoxic phenotype. Taken together, these data indicate that microglial neurotransmitter receptors can signal via Nox to promote neuroprotection or neurotoxicity. This has implications for the subsequent neurotoxic profile of microglia when neurotransmitter levels may become skewed in neurodegeneration.


Stress and Affect as Daily Risk Factors for Substance Use Patterns: an Application of Latent Class Analysis for Daily Diary Data.
At the population level, use of multiple substances (or "co-use") is prevalent in young adulthood and linked with increased risk for experiencing substance-related harms. Less understood is the heterogeneity of substance use behaviors within individuals and across days, as well as the proximal predictors of these daily use patterns. The present study applied latent class analysis to daily diary data to identify daily substance use patterns and compare day-level class membership based on day-level stress and positive and negative affect among a higher-risk sample of young adult substance users. Participants (n = 152) completed up to 13 daily assessments of stress, affect, and substance use behavior. Among substance use days, five classes of days were identified: cannabis (some alcohol; 43% of days), alcohol-only (26%), vaping (some alcohol, cannabis; 24%), stimulant + alcohol (some cannabis, vaping; 4%), and cigarette-only (3%) days. Days with lower levels of perceived stress were significantly more likely to be alcohol-only Days relative to being days characterized by cigarette use, cannabis use, or multiple drug combinations. Days with higher levels of stress and negative affect were more likely to be cigarette-only days relative to cannabis and vaping days. Study findings document the wide range of substance use and co-use behaviors exhibited among young adults in daily life and highlight the importance of considering risk factors that correspond to days of problematic use patterns.


Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
We conducted this study to evaluate the effect of disease localization on the anthropometric and metabolic characteristics of inactive Crohn's disease (CD). Forty-three patients with biopsy or radiology proven CD (23 men; age, 33.8 yr; range, 18-54 yr) in clinical remission (simplified Crohn's diseases activity index [SCDAI] < 3) and not receiving steroid therapy or nutritional support were enrolled in the study. Patients were separated into three subgroups according to disease localization: ileal (n = 16), ileo-colonic (n = 13), and colonic CD (n = 14). Sixty healthy volunteers (26 men; age, 32.0 yr; range, 18-60 yr), matched for age and height were used as control subjects. Body composition was assessed by both anthropometry and bioimpedance analysis and indirect calorimetry was performed to measure energy expenditure and substrate oxidation rates. CD patients showed a lower body weight than controls, both as a whole (61.5 kg; range, 41.5-74.0 vs 66.9 kg; range, 55.0-86.0 kg; p < 0.001) and separated by disease localization (ileal; p < 0.001; ileo-colonic; p < 0.001; and colonic; p < 0.05 vs controls). Fat-free mass (FFM) did not differ between the groups, whereas fat mass was significantly lower in CD patients than in controls (p < 0.001), with the lowest values in ileal and ileo-colonic patients. Basal metabolic rate by kg of FFM was higher in CD patients than in healthy individuals (p < 0.01). Nonprotein respiratory quotient was significantly lower in CD than in controls as a whole (0.79; range, 0.73-0.84 vs 0.83; range, 0.79-0.89; p < 0.001) or separated by disease localization (p < 0.001 each subgroup vs controls), with a consequent higher lipid oxidation rate. A lower dietary lipid intake was found in patients than in controls (p < 0.01). Regardless of disease localization, CD patients showed a lower fat mass and a higher utilization of lipids than control subjects. Patients with ileal and ileo-colonic disease showed the greater reduction in body weight, compared with control subjects, suggesting they were at a higher risk of malnutrition, probably as a consequence of the simultaneous occurrence of both malabsorption and decreased energy intake.


Retained orbital wooden foreign body: a surgical technique and rationale.
To emphasize the potential complications of a retained orbital wooden foreign body (WFB) and the rationale of a surgical technique. Two interventional case reports. Two patients sustained an orbital WFB injury. Both patients had ocular complications despite repeated attempts to remove the suspected residues. Computed tomography and magnetic resonance imaging of both patients at different intervals revealed evidence of orbital foreign body migration toward the cranium. A surgical technique combing transcranial and orbital approaches was used to remove the residues. Preoperative and postoperative vision, proptosis, ocular motility, and various ocular symptoms and signs. In both patients, no postoperative complications were seen, and all preoperative symptoms and signs were resolved at 9- and 19-month follow-ups, respectively. A retained orbital WFB can cause early or late complications and is known to have the potential to migrate intracranially. In selected patients, a team approach may be the best technique to ensure complete removal.


Comparison of Mini-FLOTAC, Flukefinder and sedimentation techniques for detection and quantification of Fasciola hepatica and Calicophoron daubneyi eggs using spiked and naturally infected bovine faecal samples.
Fasciolosis (Fasciola hepatica) and paramphistomosis (Calicophoron daubneyi) are two important infections of livestock. Calicophoron daubneyi is the predominant Paramphistomidae species in Europe, and its prevalence has increased in the last 10-15 years. In Italy, evidence suggests that the prevalence of F. hepatica in ruminants is low in the southern part, but C. daubneyi has been recently reported at high prevalence in the same area. Given the importance of reliable tools for liver and rumen fluke diagnosis in ruminants, this study evaluated the diagnostic performance of the Mini-FLOTAC (MF), Flukefinder(R) (FF) and sedimentation (SED) techniques to detect and quantify F. hepatica and C. daubneyi eggs using spiked and naturally infected cattle faecal samples. Briefly, negative bovine faecal samples were artificially spiked with either F. hepatica or C. daubneyi eggs to achieve different egg count levels: 10, 50 and 100 eggs per gram (EPG) of faeces. Moreover, ten naturally infected cattle farms from southern Italy with either F. hepatica and/or C. daubneyi were selected. For each farm, the samples were analysed individually only with MF technique and as pools using MF, FF and SED techniques. Bayesian latent class analysis (LCA) was used to estimate sensitivity and accuracy of the predicted intensity of infection as well as the infection rate in the naturally infected farms. The outcome of this study showed that the highest number of eggs (F. hepatica and C. daubneyi) recovered was obtained with MF, followed by FF and SED in spiked infected samples at 50 and 100 EPG, while at lower infection levels of 10 EPG, FF gave the best results. Moreover, the sensitivity for all the techniques included in the study was estimated at > 90% at infection levels > 20 EPG for both F. hepatica and C. daubneyi eggs. However, MF was the most accurate of the three techniques evaluated to estimate fluke infection intensity. Nevertheless, all three techniques can potentially estimate infection rate at farm level accurately. Optimization and standardization of techniques are needed to improve the FEC of fluke eggs.


[The value of arthroscopy for diagnosis of instability of the shoulder joint].
As a glenohumeral instability is defined each case of transient recurrent and permanent decentration of the joint. We propose to differentiate primary and secondary glenohumeral instabilities. Arthroscopical diagnostic is helpful to classify the luxation and subluxation and for verify transient instabilities. In cases clinically snapping phenomena were noticed, arthroscopic findings were documented. A relation between those phenomena and arthroscopic findings is discussed.


Impact of the Severity of Liver Injury in COVID-19 Patients Admitted to an Intensive Care Unit During the SARS-CoV2 Pandemic Outbreak.
The World Health Organization (WHO) identified a novel coronavirus, originating in Wuhan, China, in December 2019, as a pneumonia causing pathogen. Epidemiological data in Romania show more than 450.000 confirmed patients, with a constant number of approximately 10% admission in intensive care unit. A retrospective, observational study was conducted from 1st March to 30th October 2020, comprising 657 patients, confirmed as having COVID-19, and who had been admitted to the intensive care unit of the Mures County Clinical Hospital, Tîrgu Mures, Romania, which had been designated as a support hospital during the pandemic. Patients who presented at admission or developed abnormal liver function tests in the first seven days of admission, were included in the study; patients with pre-existing liver disease, were excluded. The mean (SD) age of patients included in the study was 59.41 (14.66) years with a male: female ratio of 1.51:1. Survivor status, defined as patients discharged from the intensive care unit, was significantly associated with parameters such as age, leukocyte count, albumin level, glycaemia level (p<0.05 for all parameters.). Liver injury expressed through liver function tests cannot solely constitute a prognostic factor for COVID-19 patients, but its presence in critically ill patients should be further investigated and included in future guideline protocols.


Intrapartum uterine activity and neonatal outcomes: a systematic review.
Increased uterine activity (UA) may not allow adequate recovery time for foetal oxygenation. The aim of the study was to determine if increased UA during labour is associated with an increased risk of either short- or long-term neurological injury in term neonates, or with neonatal proxy measures of intrapartum hypoxia-ischemia. MEDLINE, CINAHL, and ClinicalTrials.gov were searched using the following terms: uterine activity, excessive uterine activity, XSUA, uterine hyperstimulation, and tachysystole. Any study that analysed the relationship between UA during term labour and neurological outcomes/selected proxy neurological outcomes was eligible for inclusion. Outcomes from individual studies were reported in tables and presented descriptively with odds ratios (OR) and 95% confidence intervals (CI) for dichotomous outcomes and means with standard deviations for continuous outcomes. Where group numbers were provided, ORs and their CIs were calculated according to Altman. Twelve studies met the inclusion criteria. Seven studies featured umbilical artery pH as an individual outcome. Umbilical artery base excess and Apgar scores were both reported as individual outcomes in four studies. No study examined long term neurodevelopmental outcomes and only one study reported on encephalopathy as an outcome. The evidence for a relationship between UA and adverse infant outcomes was inconsistent. The reported estimated effect size varied from non-existent to clinically significant. There is some evidence that increased UA may be a non-specific predictor of depressed neurological function in the newborn, but it is inconsistent and insufficient to support the conclusion that an association generally exists.


Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure.
We examined the effects of chronic type A endothelin receptor (ETA) blockade in a dog model of pacing-induced cardiomyopathy. Eight dogs received an ETA antagonist, LU 135252 (50 mg/kg orally daily) and nine dogs received a matching placebo starting at day three of pacing and continued for the remainder of the three weeks of pacing. In the placebo group, the mean pulmonary artery pressure and left ventricular end diastolic pressure increased from 16 +/- 3 and 8 +/- 2 mmHg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mmHg, respectively, at two weeks (both p < 0.001 versus baseline). Cardiac output declined from 3.5 +/- 0.7 to 1.9 +/- 0.6 l/min (p < 0.001). In the treatment group, LU 135252 attenuated the increase in mean pulmonary artery and left ventricular end diastolic pressure (16 +/- 3 and 9 +/- 1 mmHg at baseline to 29 +/- 3 and 27 +/- 3 mmHg, respectively, at two weeks (p < 0.001), and the decline in cardiac output (3.2 +/- 0.3 to 2.6 +/- 0.8 l/min, p < 0.01; p < 0.05 versus placebo for the three parameters). Systemic and pulmonary vascular resistance increased only in the placebo group. Left ventricular end-diastolic volume increased to a similar degree. However, LU 135252 attenuated the increase in plasma norepinephrine level (placebo, 1.2 +/- 0.5 to 3.7 +/- 1.9 pmol/l; treatment, 0.8 +/- 0.3 to 2.4 +/- 0.6 pmol/l; both p < 0.001 versus baseline; p < 0.05 versus placebo). Our results suggest that endothelin-1 plays a role in the hemodynamic perturbations in canine pacing-induced cardiomyopathy. The favourable hemodynamic effects without concomitant aggravation of neurohormonal activation suggests that ETA receptor blockade may be beneficial in the treatment of heart failure.


[Role of lipid peroxidation in damage to brain neurons during ischemia and in the postischemic period].
It has been demonstrated in experiments on rats that highly activated lipid peroxidation in brain tissue during ischemia and early postischemic period gives rise to injuries of membrane structures of neurons and to formation of lysosomes that subsequently aggravate neuronal destruction.


Factors affecting female college students' intention to use digital technology in wearable devices to stimulate health monitoring.
In this study, we measured female college students' mental health and physical activities to identify factors that affect their intention to use wearable health-monitoring devices. Specifically, the study derived correlations between female students' health-related quality of life (HRQoL) including, physical activity, stress level, attitudes toward eating, and self-esteem. Using this information, we ascertained the relationship between female college students' use of wearable devices and physical activity and examined the requirements for smartphone applications for healthcare. We collected data from 308 female college students in the Republic of Korea over four months starting in July 2021 using an anonymous online survey. We then analyzed the data using descriptive statistics and linear regression. The results showed that the factors that caused stress in female college students during the past six months were fatigue, COVID-19, grades, worries about getting a full-time job, menstruation, and being overweight. This paper found a negative correlation between stress and self-esteem and a positive correlation between physical activity and self-esteem. People with experience using wearable devices reported a higher intensity in physical activity. More than half the participants recorded biometric information for their menstrual cycles and menstrual cramps regardless of whether they were using wearable devices. Currently, healthcare applications can suggest diets and track nutritional intake, menstrual cycles, and amount of exercise, which users want simultaneously. Therefore, there is a market demand for a mobile application linked with a wearable device and tailored for female college students that could combine and manage all these data. In the future, application developers should consider the needs of female college students.


Long-term risk factors for substance-induced and primary psychosis after release from prison. A longitudinal study of substance users.
The purpose of this study was to determine long-term risk factors for substance-induced and primary psychosis after release from prison. We used a longitudinal register-based cohort study combining European version of Addiction Severity Index (Europ-ASI) interviews and the Swedish inpatient register. The study included 6217 individuals who were in the Swedish criminal justice system from 2001 to 2006. The outcomes were substance-induced and primary psychosis as defined by the International Classification of Disease - 10th version. All variables for estimating baseline risk were drawn from the Europ-ASI interview, and included information on substance use, demographics and health. The interview database and the inpatient register were coupled, and groups were compared by using tests of significance and logistic regression. Polydrug use was the strongest predictor for substance induced psychosis (OR=9.55, 95% CI 3.42-26.67), but all substances imposed an increased risk. Previous psychiatric hospitalization and non-drug related hallucinations were significant, but weaker, risk factors. The only substance variable that predicted primary psychosis was cannabis (OR=2.62, 95% CI 1.39-4.96), but previous psychiatric hospitalization (OR=3.22, 95% CI 2.27-4.54) and non-drug related hallucinations (OR=4.00, 95% CI 2.82-5.67) were even stronger predictors. Cannabis use was a risk factor for primary psychosis, but other health related individual risk factors were even more important. Polydrug use was the strongest risk factor for substance-induced psychosis.


Evaluating Measurement Properties of Patient-Reported Outcome Measures in Glaucoma: A Systematic Review.
The purpose of the current study was to systematically identify and evaluate existing patient-reported outcome measures (PROMs) for clinical glaucoma practice. Understanding and incorporating patient preferences into decision-making is now recognized as critical for optimal resource allocation, especially in technologically advancing areas, such as minimally invasive surgeries. Patient-reported outcome measures are instruments designed to evaluate the health outcomes that are most important to patients. Despite their recognized importance, especially in the era of patient-centered care, their routine use in clinical settings remains low. A systematic literature search was conducted in 6 databases (EMBASE, MEDLINE, PsycINFO, Scopus, BIOSIS, and Web of Science) from the date of inception. Studies were included in the qualitative review if they reported measurement properties of PROMs in adult patients with glaucoma. COnsensus-based Standards for the selection of health Measurement INstruments guidelines were used to assess the included PROMs. The study protocol is registered with PROSPERO (registration number: CRD42020176064). The literature search yielded 2661 records. After deduplication, 1259 studies entered level 1 screening, and based on title and abstract review, 164 records proceeded to full-text screening. In 48 included studies, 70 instrument reports discuss 43 distinct instruments in 3 major categories: glaucoma-specific, vision-specific, and general health-related quality of life. Most used measures were glaucoma-specific (Glaucoma Quality of Life [GQL] and Glaucoma Symptom Scale [GSS]) and vision-specific (National Eye Institute Visual Function Questionnaire [NEI VFQ-25]). All 3 have sufficient validity (especially construct), with GQL and GSS having sufficient internal consistency, cross-cultural validity, and reliability, with reports suggesting high methodological quality. The GQL, GSS, and NEI VFQ-25 are the 3 most used questionnaires in a research setting, having considerable validation in a patient population with glaucoma. Limited reports on interpretability, responsiveness, and feasibility in all 43 identified instruments make identifying a single optimal questionnaire for clinical use challenging and highlight the need for further studies. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


SCREENING OF WILD FRUIT TREES WITH GASTROPROTECTIVE ACTIVITY IN DIFFERENT EXPERIMENTAL MODELS.
Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.


Perceived prenatal learning needs of multigravid Ghanaian women.
to explore the learning needs of multigravid Ghanaian women in an effort to develop more effective prenatal education programmes. a descriptive-exploratory design consisting of in-depth individual semi-structured interviews and a single focus group. prenatal clinic of a large hospital in a city in Ghana, Africa. 18 multigravid Ghanaian women between 38 and 40 weeks of gestation who were not experiencing complications with the index pregnancy. the women reported particular learning needs that were not being addressed during their prenatal care. They identified areas where they wanted more information about specific topics such as birth control, sexual activity during pregnancy and promoting ideal fetal positions. They also wanted information about how to care for themselves and their babies after birth. They received information from staff at the prenatal clinic that sometimes conflicted with what they learned from those in their informal support system (e.g. mothers and friends). inconsistency with respect to information received from health professionals and that received from other sources of support created tension that led to increased doubt and anxiety on the part of the women. They reported that they wanted more in-depth information that was relevant to their specific needs and solution centred. They wanted a more interactive educational process including some separate teaching sessions specifically for multigravid women. They also wanted access to information during both private and group encounters with health-care professionals. information and strategies deemed to be of interest and importance to these multigravid women, such as private counselling sessions to address individual concerns about safe sexual health and birth control, and interactive groups for multigravid women, could be implemented to increase interest and promote the well-being of these women.


Rocuronium ≤1.5 mg/kg versus >1.5 mg/kg and inadequate paralysis in prehospital and retrieval intubation: A retrospective study.
Greater Sydney Area Helicopter Emergency Medical Service encouraged an increased dose of rocuronium for rapid sequence intubations (RSIs) from 1.5 mg/kg to 2.0 mg/kg from the end of 2017 in response to a number of inadequately paralysed patients identified by our airway audit processes. Subsequent protocol change incorporated 2.0 mg/kg rocuronium. This retrospective observational study was undertaken to see if doses over 1.5 mg/kg rocuronium were associated with a reduction in the number of inadequately paralysed patients. Retrospective review of patient prehospital notes and airway database records from 2017 to 2018 for all cases using rocuronium for RSI. Primary outcome of interest was physician notes describing skeletal muscle activity at laryngoscopy. Patients with tissued vascular access were excluded. Dose of rocuronium, estimated patient actual weight and grade of laryngoscopy were recorded. Comparisons were made between rocuronium doses ≤1.5 mg/kg and >1.5 mg/kg by estimated weight. From 211 patients receiving rocuronium ≤1.5 mg/kg, five cases were inadequately paralysed, compared with two cases from 384 patients receiving >1.5 mg/kg rocuronium. Although there were fewer inadequately paralysed patients with rocuronium doses >1.5 mg/kg, this did not reach statistical significance, presumably because of the low event rate. Further investigation into rocuronium dose for RSI is warranted.


The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration.
Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP). Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay). A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060). Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE.


Epigenetic drug ameliorated type 1 diabetes via decreased generation of Th1 and Th17 subsets and restoration of self-tolerance in CD4+ T cells.
Female NOD mice develop autoimmune diabetes spontaneously without extrinsic manipulation. Previously, we have shown that weekly administration of the prediabetic female NOD mice with the histone modifier Trichostatin A (TSA) prevented diabetes onset. Herein we show that T lymphocytes from diabetic mice transferred diabetes into immunodeficient NOD.scid recipients while those isolated from drug-treated mice displayed reduced disease-causing ability. Drug treatment also repressed T cell receptor-mediated IFN-γ transcription. Splenic CD4+ T-cells purified from prediabetic mice could be polarized into IFN-γ -producing Th1 and IL-17A-expressing Th17 subsets ex vivo. Adoptive transfer of these cells into immunocompromised NOD.scid mice caused diabetes comparably. Polarized Th1 cells were devoid of IL-17A-producing cells and did not transdifferentiate into Th17 cells in the spleen of immunodeficient recipients. However, polarized Th17 cell preparation had a few contaminant Th1 cells. Adoptive transfer of polarized Th17 cells into NOD.scid recipients led to IFN-γ transcription in recipient splenocytes. Notably, TSA treatment of prediabetic mice abolished the ability of CD4+ T-cells to differentiate into diabetogenic Th1 and Th17 cells ex vivo. This was accompanied by the absence of Ifng and Il17a transcription in the spleen of NOD.scid recipients receiving cells, respectively cultured under Th1 and Th17 polarizing conditions. Significantly, the histone modifier restored the ability of CD4+ but not CD8+ T-cells to undergo CD3-mediated apoptosis ex vivo in a caspase-dependent manner. These results indicate that the histone modifier bestowed protection against type 1 diabetes via negative regulation of signature lymphokines and restitution of self-tolerance in CD4+ T cells.


Effects of Hoechst 33258 on different cell cycle events. I. Inhibition of synthetic activities in bone-marrow cells of the mole rat Bandicota bengalensis.
A study of the effects of the A-T base-specific ligand Hoechst 33258 on the cell cycle events of the bone-marrow cells of the mole rat Bandicota bengalensis reveals that (1) the G2 phase is prolonged by 2 h; (2) the chromosomes are undercondensed to varying degrees in about 30% metaphases; (3) DNA as well as RNA synthesis is partially inhibited. Study on DNA fibre autoradiograms shows that despite the inhibition of DNA synthesis the average replicon size and rate of fork migration remain unchanged, but there is a marked asynchrony of initiation of replicons in replicon clusters in H-treated cells in comparison with control. It is suggested that these inhibitory effects result from the stabilization of the double-stranded organization of DNA (dsDNA) by the drug so that the unwinding of DNA at the replication or transcription origin sites is greatly impaired. It is likely that this introduces asynchrony in the initiation of replicons within replicon clusters which may retard the overall rate of replication. In addition, it appears that the reduction in transcription is at least one cause for the prolongation of G2 phase.


Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn.
Root powder of Achyranthes aspera Linn. (A. aspera) belongs to family Amaranthaceae is used in Indian traditional medicine for the management of epilepsy and its efficacy is widely acclaimed among the different rural communities. The present study was aimed to establish the possible anticonvulsant effect of A. aspera methanolic root extract using acute anticonvulsant models and to evaluate the acute toxicity and neurotoxic potential A. aspera extract. A. aspera methanolic extract was standardized with respect to betaine using HPTLC. The maximal electroshock (MES), pentylenetetrazol (PTZ), picrotoxin and bicuculline induced seizure models were used to evaluate the anticonvulsant potential of standardized A. aspera root extract. The GABA content in cortex and hippocampus of extract treated mice was evaluated using HPLC. Moreover, the animals were also evaluated for acute toxicity study and neurotoxicity test. A significant enhancement in the seizure threshold was observed by A. aspera extract (5 and 10mg/kg) treated mice in PTZ, picrotoxin and bicuculline models as compared to saline treated mice respectively, whereas the extract failed to show protection in MES induced seizures. Moreover, A. aspera treatment (5 and 10mg/kg) significantly enhances the GABA levels in hippocampus and cortex as compared to saline treated group. A. aspera root extract was devoid of any sign of acute toxicity as well as neurotoxicity. A. aspera root extract exhibits significant anticonvulsant effect by facilitation of GABAergic neurotransmission in the brain.


Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy.
Hydrodynamics-based gene transfer has been successfully employed for in vivo gene delivery to the liver of small animals by tail vein injection and of large animals using a computer-assisted and image-guided protocol. In an effort to develop a hydrodynamic gene delivery procedure clinically applicable for gene therapy, we have evaluated the safety and effectiveness of a lobe-specific hydrodynamic delivery procedure for hepatic gene delivery in baboons. Reporter plasmid was used to assess the gene delivery efficiency of the lobe-specific hydrodynamic gene delivery, and plasmid-carrying human factor IX gene was used to examine the pattern of long-term gene expression. The results demonstrated liver lobe-specific gene delivery, therapeutic levels of human factor IX gene expression lasting for >100 days, and the efficacy of repeated hydrodynamic gene delivery into the same liver lobes. Other than a transient increase in blood concentration of liver enzymes right after the injection, no significant adverse events were observed in animals during the study period. The results obtained from this first non-human primate study support the clinical applicability of the procedure for lobe-specific hydrodynamic gene delivery to liver.


Proton MR properties of lyophilized urine samples from normal and stone former individuals.
Proton MR measurements were performed in lyophilized urine samples collected from 5 normals (N) and 5 idiopathic hypercalciuric recurrent stone formers (SF). T1 and T2 relaxation times were measured with a Bruker PC Multispec at 20 MHz and 37 degrees C in the lyophilized samples and in samples gradually rehydrated. Significantly (p less than 0.01) prolonged T1 and T2 relaxation times were measured after addition of water to the lyophilized samples. The relaxation time prolongation patterns were significantly different (p less than 0.01) for the two groups; the rehydration curves of the lyophilized urine samples from the SF group had relatively shorter lag than that of N group. In calculations of water compartmentalization for similar water content, significant (p less than 0.01) differences in the fraction of bound water (FB) were found between the two groups. These results may reflect differences in the macromolecular properties, contents, in the amount of water binding sites and/or in the water multilayer thickness between the two groups. These differences, expressed as changes of the relaxation times values may provide new diagnostic possibilities of different renal pathologies.


Chicken-type lysozyme is a major bacteriolytic enzyme in the blood of the banded houndshark Triakis scyllium.
We examined lysozyme activities in the serum and the leukocyte extracts of the banded houndshark Triakis scyllium. The serum exhibited lytic activity, but not the leukocyte extracts. The lytic substance in the serum was of approximately 14 kDa and the N-terminal amino acid sequence was YVYSK. cDNA cloning identified a C-type lysozyme (TsLysC) gene and two G-type lysozyme (TsLysG) cDNA clones of different lengths. The TsLysC gene encodes 149 amino acids residues, and the sequence derived from the N-terminal amino acid sequencing was displayed at position 17-21. TsLysG, on the other hand, contains two ORFs that are homologous to the N- and C-terminal regions of G-type lysozyme of other fish species. TsLysC mRNA levels were high in the liver. TsLysG mRNA level was significantly lower than TsLysC mRNA in the liver.


[Epidemiological situation of children' intestinal infections in Malopolska Voivodeship regarding to new possibilities of rotavirus prevention].
Rotavirus is the main etiological cause of intestinal infections in children. The voluntary rotavirus vaccines was included to Polish vaccination schedule in 2007. The aim of this study was assessment of epidemiological situation of intestinal infections in children up to two years in Malopolska Voivodeship regarding the population influence of rotavirus vaccinations on the number ofrotavirus infections. For entire area included to evaluation, despite the increasing vaccination coverage in children the number of notified rotaviruses infections revealed the rising trend, as well. The results have not showed the population influence of voluntary rotavirus vaccinations on the incidence of intestinal infections in the youngest children.


FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis.
Immune checkpoint blockade of the programmed cell death protein 1 (PD-1) pathway by monoclonal antibodies (Abs) has shown promising clinical benefit in the treatment of multiple cancer types. We elucidated the contribution of the fragment crystallizable (Fc) domains of anti-PD-1 and anti-PD-ligand 1 (L1) Abs for their optimal anti-tumor activity. We revealed that distinct Fcγ receptor (FcγRs) dependency and mechanisms account for the in vivo activity of anti-PD-1 versus anti-PD-L1 Abs. Anti-PD-1 Abs were found to be FcγR independent in vivo; the presence of FcγR-binding capacity compromises their anti-tumor activity. In contrast, the anti-PD-L1 Abs show augmented anti-tumor activity when activating FcγR binding is introduced into the molecules, altering myeloid subsets within the tumor microenvironment.


The clinical characteristics of neuropathic pain in patients with total brachial plexus avulsion: A 30-case study.
Neuropathic pain in patients with total brachial plexus avulsion has always been a sophisticated problem in clinical practice. For further researches on objective diagnosis, alleviation or even cure of neuropathic pain, we need to conclude the basic clinical features including pain intensity, distribution, type and possible risk factors. Thirty cases of patients with total brachial plexus avulsion were included and their baseline information was collected. Pain was evaluated by Present Pain Index using a visual analog scale; Douleur Neuropathique 4 was used for screening neuropathic pain. For more detailed pain description, the Neuropathic Pain Symptoms Inventory questionnaire and a picture showing the exact pain district were both fulfilled by all the eligible participants. The relationship between neuropathic pain and basic information, injury conditions, accompanied conditions and quality of life was tested. All the participants were male in both groups. The neuropathic pain group contained 22 patients (73.33%) with the mean age of 30.18±9.47; while 29.00±7.95 in the other group. Patients with neuropathic pain presented variously in pain degree, location, type and time phase, according to the results of the Neuropathic Pain Symptoms Inventory questionnaire. Nevertheless, most pain distributed on the region of hand. Among several related factors, alcohol abuse may be possible risk factors of neuropathic pain (p=0.03). Quality of life was significantly affected by pain (p<0.01). Neuropathic pain in patients with total brachial avulsion was characterized with heterogeneity in pain distribution, intensity, type and also time phase. Bad life habits might be risk factors associated with neuropathic pain. Neuropathic pain might affect quality of life of the patients with total brachial plexus avulsion remarkably.


An overview of the wcd EST clustering tool.
The wcd system is an open source tool for clustering expressed sequence tags (EST) and other DNA and RNA sequences. wcd allows efficient all-versus-all comparison of ESTs using either the d(2) distance function or edit distance, improving existing implementations of d(2). It supports merging, refinement and reclustering of clusters. It is 'drop in' compatible with the StackPack clustering package. wcd supports parallelization under both shared memory and cluster architectures. It is distributed with an EMBOSS wrapper allowing wcd to be installed as part of an EMBOSS installation (and so provided by a web server). wcd is distributed under a GPL licence and is available from http://code.google.com/p/wcdest. Additional experimental results. The wcd manual, a companion paper describing underlying algorithms, and all datasets used for experimentation can also be found at www.bioinf.wits.ac.za/~scott/wcdsupp.html.


Sniffing animals as a diagnostic tool in infectious diseases.
Scents and odours characterize some microbes when grown in the laboratory, and experienced clinicians can diagnose patients with some infectious diseases based on their smell. Animal sniffing is an innate behaviour, and animals' olfactory acuity is used for detecting people, weapons, bombs, narcotics and food. We briefly summarized current knowledge regarding the use of sniffing animals to diagnose some infectious diseases and the potential use of scent-based diagnostic instruments in microbiology. Information was sought through PubMed and extracted from peer-reviewed literature published between January 2000 and September 2019 and from reliable online news. The search terms 'odour', 'scent', 'bacteria', 'diagnostics', 'tuberculosis', 'malaria' and 'volatile compounds' were used. Four major areas of using sniffing animals are summarized. Dogs have been used to reliably detect stool associated with toxigenic Clostridioides difficile and for surveillance. Dogs showed high sensitivity and moderate specificity for detecting urinary tract infections in comparison to culture, especially for Escherichia coli. African giant pouched rats showed superiority for diagnosing tuberculosis over microscopy, but inferiority to culture/molecular methods. Several approaches for detecting malaria by analysing host skin odour or exhaled breath have been explored successfully. Some microbial infections produce specific volatile organic compounds (VOCs), which can be analysed by spectrometry, metabolomics or other analytical approaches to replace animal sniffing. The results of sniffing animal studies are fascinating, and animal sniffing can provide intermediate diagnostic solutions for some infectious diseases. Lack of reproducibility, and cost of animal training and housing are major drawbacks for wider implementation of sniffing animals. The ultimate goal is to understand the biological background of this animal ability and to characterize the specific VOCs that animals are recognizing. VOC identification, improvement of odour sampling methods and development of point-of-care instruments could allow implementation of scent-based tests for major human pathogens.


Neurologic Diseases in Special Care Patients.
Neurologic diseases can have a major impact on functional capacity. Patients with neurologic disease require individualized management considerations depending on the extent of impairment and impact on functional capacity. This article reviews 4 of the more common and significant neurologic diseases (Alzheimer disease, cerebrovascular accident/stroke, multiple sclerosis, and Parkinson disease) that are likely to present to a dental office and provides suggestions on the dental management of patients with these conditions.


Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons.
Topiramate is a widely used antiepileptic agent whose mechanism of action is poorly understood. The drug has been reported to interact with various ion channel types, including AMPA/kainate receptors. In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, topiramate at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the GluR5 subunit. Topiramate also partially depressed predominantly AMPA-receptor-mediated EPSCs, but with lower efficacy. Topiramate did not alter the degree of facilitation in paired-pulse experiments, and it reduced the amplitude of miniature EPSCs without affecting their frequency, demonstrating that the block of synaptic responses occurs postsynaptically. Inhibition of GluR5 kainate receptors could represent a key mechanism underlying the anticonvulsant activity of topiramate. Moreover, these results support the concept that GluR5 kainate receptors represent a novel target for antiepileptic drug development.


High-throughput and high-accuracy single-cell RNA isoform analysis using PacBio circular consensus sequencing.
Although long-read single-cell RNA isoform sequencing (scISO-Seq) can reveal alternative RNA splicing in individual cells, it suffers from a low read throughput. Here, we introduce HIT-scISOseq, a method that removes most artifact cDNAs and concatenates multiple cDNAs for PacBio circular consensus sequencing (CCS) to achieve high-throughput and high-accuracy single-cell RNA isoform sequencing. HIT-scISOseq can yield >10 million high-accuracy long-reads in a single PacBio Sequel II SMRT Cell 8M. We also report the development of scISA-Tools that demultiplex HIT-scISOseq concatenated reads into single-cell cDNA reads with >99.99% accuracy and specificity. We apply HIT-scISOseq to characterize the transcriptomes of 3375 corneal limbus cells and reveal cell-type-specific isoform expression in them. HIT-scISOseq is a high-throughput, high-accuracy, technically accessible method and it can accelerate the burgeoning field of long-read single-cell transcriptomics.


Adherent cells as targets in mitogenic T-lymphocyte stimulation: replacement of lymphocyte-bound mitogens by nonmitogenic substances.
The sequence of events in mitogenic T-lymphocyte activation was investigated by employing purified mouse peritoneal adherent cells and T-lymphocyte populations. After treatment of adherent cells with the oxidizing agents sodium periodate or neuroaminidase plus galactose oxidase and removal of the mitogens, the cells acquired the ability to stimulate purified T-lymphocytes added subsequently. For this process of T-lymphocyte activation, the additional presence of the membrane interacting substances polyethylene glycol, dextran, nonmitogenic Helix pomatia agglutinin, or inactivated sendai virus was required. Lysates of mitogen-treated peritoneal adherent cells were able to replace the adherent cells in the cultures.


[Late results of the surgical treatment of calculus-free cholecystitis].
On the grounds of the experience with 72 cases of non-calculous cholecystitis the authors describe the characteristic features and sequelae of the disease. The authors recommend to use endoscopy methods widely with the goal to differentiate this pathology from any other biliary pancreato-duodenal pathology in order to elaborate adequate surgical indications for patients suffering from non-calculous cholecystitis.


Efficacy and safety of a single dose therapy of a 500 mg ciprofloxacin tablet in chancroid patients.
A single dose therapy of 500 mg ciprofloxacin was sufficient to cure 15 of 18 chancroid patients within six days and the remaining three within 7, 11 and 20 days respectively. The drug was well tolerated, and no serious side effects were observed. The MICs of ciprofloxacin for the isolated Haemophilus ducreyi strains ranged from 0.0015 to 0.02 mg/l (mean 0.01 mg/l). It may therefore be concluded from our study that the oral administration of ciprofloxacin to chancroid patients with or without buboes is highly effective and free from side effects.


Systematic review on the prevalence of perinatal depression in Malawi.
Perinatal depression causes significant burden to women and their families during the perinatal period. However, there is no reliable national prevalence data on perinatal depression in Malawi. This systematic review aimed at establishing the pooled prevalence of perinatal depression. The study setting is Malawi. Two reviewers conducted the search, selection, quality evaluation and data abstraction. Appropriate terms were used to search the CINAHL, PsychINFO, PubMed and ScienceDirect databases. The relevance and the quality of the studies were assessed. The prevalence of prenatal depression was pooled using a random-effects model, which was used to synthesise the data. The review included a total of eight articles of fair and good quality. This review found a pooled prevalence of antenatal depression of 17.1% (95.0% confidence interval [CI]: 12.5-22.2) and postnatal depression of 19.8% (95.0% CI: 4.6-42.1) with an overall pooled prevalence of perinatal depression of 18.9% (95.0% CI: 14.5-23.8). This systematic review provided a pooled prevalence of perinatal depression which may be used in the absence of national prevalence data on perinatal depression. This systematic review found a high a pooled prevalence of perinatal depression in Malawi suggesting that mental health should be a key component of maternal health programmes, policies and activities in the local setting.


Biological monitoring of workers exposed to N,N-dimethylformamide by determination of the urinary metabolites, N-methylformamide and N-acetyl-S-(N-methylcarbamoyl) cysteine.
Biological monitoring of workers exposed to N,N-dimethylformamide (DMF) was carried out by determination of the urinary metabolites, N-methylformamide (MF, mainly from N-hydroxymethylformamide) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), which were derived from two different routes of metabolism of the solvent. The urinary levels of MF increased rapidly at the start of the work shift, and decreased almost to zero within 24 h after the beginning of the last exposure. The highest level was found between the end of the afternoon shift and bedtime. AMCC levels remained constant over the consecutive work days and increased after the cessation of exposure, with the peak concentration being observed at 16-40 h after the cessation of exposure. AMCC levels at the beginning of the next morning shift were closely correlated with personal exposure levels of DMF in air, although the correlation of MF and DMF in air was highest in the urine at the end of the shift. Hence urinary AMCC represents an index of the average exposure during several preceding work days and may indicate the internal dose. By contrast, MF represents an index of daily exposure.


Characterization and distribution of GHRH, PACAP, TRH, SST and IGF1 mRNAs in the green iguana.
The somatotropic axis (SA) regulates numerous aspects of vertebrate physiology such as development, growth, and metabolism and has influence on several tissues including neural, immune, reproductive and gastric tract. Growth hormone (GH) is a key component of SA, it is synthesized and released mainly by pituitary somatotrophs, although now it is known that virtually all tissues can express GH, which, in addition to its well-described endocrine roles, also has autocrine/paracrine/intracrine actions. In the pituitary, GH expression is regulated by several hypothalamic neuropeptides including GHRH, PACAP, TRH and SST. GH, in turn, regulates IGF1 synthesis in several target tissues, adding complexity to the system since GH effects can be exerted either directly or mediated by IGF1. In reptiles, little is known about the SA components and their functional interactions. The aim of this work was to characterize the mRNAs of the principal SA components in the green iguana and to develop the tools that allow the study of the structural and functional evolution of this system in reptiles. By employing RT-PCR and RACE, the cDNAs encoding for GHRH, PACAP, TRH, SST and IGF1 were amplified and sequenced. Results showed that these cDNAs coded for the corresponding protein precursors of 154, 170, 243, 113, and 131 amino acids, respectively. Of these, GHRH, PACAP, SST and IGF1 precursors exhibited a high structural conservation with respect to its counterparts in other vertebrates. On the other hand, iguana's TRH precursor showed 7 functional copies of mature TRH (pyr-QHP-NH2), as compared to 4 and 6 copies of TRH in avian and mammalian proTRH sequences, respectively. It was found that in addition to its primary production site (brain for GHRH, PACAP, TRH and SST, and liver for IGF1), they were also expressed in other peripheral tissues, i.e. testes and ovaries expressed all the studied mRNAs, whereas TRH and IGF1 mRNAs were observed ubiquitously in all tissues considered. These results show that the main SA components in reptiles of the Squamata Order maintain a good structural conservation among vertebrate phylogeny, and suggest important physiological interactions (endocrine, autocrine and/or paracrine) between them due to their wide peripheral tissue expression.


Differential sensitivity to cocaine in spontaneously hypertensive and Wistar-Kyoto rats.
Physiological, pharmacological and toxicological responses to two regimens of cocaine administration were compared between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. An initial experiment examined renal excretory and hemodynamic function in response to an acute volume load in anesthetized SHR and WKY following subacute cocaine treatment (20 mg/kg, s.c., twice a day for 9 days). Anticipated renal responses to volume loading were obtained but the responses of cocaine-treated SHR and WKY did not differ from vehicle-treated rats. A second group of experiments compared responses to continuous i.v. infusions of cocaine (1.25 mg/kg.min). In freely moving animals, no differences were noted between SHR and WKY in the increases in mean blood pressure (MBP) and heart rate (HR) produced during cocaine infusion. The elapsed time-to-onset of convulsions (Tc) elicited by cocaine was similar in both strains. However, when rats were subjected to restraint during the infusion period, pressor and tachycardic responses were observed to be significantly less in WKY than in SHR or in freely moving rats of either strain. Restraint also differentially affected rectal temperature (RT) responses to cocaine. Hypothermic responses to cocaine were observed in all WKY. Both hypothermic and hyperthermic responses were observed in SHR. A significant correlation was demonstrated between the Tc and the maximal change in RT produced during cocaine infusion. Division of SHR into two arbitrary groups was made, based on the direction of cocaine-induced change in RT. A significant (p less than 0.01) shortening of the Tc was obvious in SHR (8 of 15) in whom cocaine produced a hyperthermia. These animals were designated SHRH. The mean value for Tc in those SHR which demonstrated a lowering in RT (SHRL; 7 of 15) in response to cocaine was similar to that for WKY. Moreover, the SHRH evidenced significantly greater increases in HR, but not MBP, to cocaine infusion than did SHRL. The results indicate that restraint stress causes expression of a significant heterogeneity in the RT response of SHR to cocaine. The magnitude and direction of the RT responses are negatively correlated with sensitivity to the convulsive effects of cocaine in SHR. Stress may modify toxic responses to cocaine by interactions with body temperature homeostasis.


Diagnosis for anterior cruciate ligament surgery.
We have reviewed the important aspects of the history, physical examination, and other diagnostic tools available to help diagnose ACL injuries. We feel that, in the hands of an experienced clinician, greater than 90% of ACL disruptions can be diagnosed at the time of injury. Appropriate evaluation will enable the clinician to advise the appropriate treatment, whether it be operative or nonoperative. We have also briefly outlined the variables that we consider to be the most important in the decision-making process of treatment options after ACL disruption.


Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma.
Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(-)-PD-L1(-) group. Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.


[Effect of thyroidectomy on bone mineral metabolism. Experimental study in rats].
The aim of the study was to ascertain the importance of calcitonin in the etiopathogenesis of osteoporosis in rats as an animal model. We used 20 female rats on which a thyroidectomy was performed, producing a calcitonin deficit. An autologous transplant of parathyroid gland and replacement therapy of thyroid hormone was carried out. The control group consisted of 20 rats. The levels of parathormone (PTH), calcitonin (CT), osteocalcin (GLA), seric calcium, and density, weight, quantity and mineral bone content of the head of the femur were measured. We found low levels of CT and normal amount of PTH, which contradicted the expected, there was an increment of the mineral bone content, without significant density, quantity and weight changes. We comment on these results.


A systematic comparison of key features of ischemic stroke prevention guidelines in low- and middle-income vs. high-income countries.
Implementation of contextually appropriate, evidence-based, expert-recommended stroke prevention guideline is particularly important in Low-Income Countries (LMICs), which bear disproportional larger burden of stroke while possessing fewer resources. However, key quality characteristics of guidelines issued in LMICs compared with those in High-Income Countries (HICs) have not been systematically studied. We aimed to compare important features of stroke prevention guidelines issued in these groups. We systematically searched PubMed, AJOL, SciELO, and LILACS databases for stroke prevention guidelines published between January 2005 and December 2015 by country. Primary search items included: "Stroke" and "Guidelines". We critically appraised the articles for evidence level, issuance frequency, translatability to clinical practice, and ethical considerations. We followed the PRISMA guidelines for the elaboration process. Among 36 stroke prevention guidelines published, 22 (61%) met eligibility criteria: 8 from LMICs (36%) and 14 from HICs (64%). LMIC-issued guidelines were less likely to have articulation of recommendations (62% vs. 100%, p=0.03), involve high quality systematic reviews (21% vs. 79%, p=0.006), have a good dissemination channels (12% vs 71%, p=0.02) and have an external reviewer (12% vs 57%, p=0.07). The patient views and preferences were the most significant stakeholder considerations in HIC (57%, p=0.01) compared with LMICs. The most frequent evidence grading system was American Heart Association (AHA) used in 22% of the guidelines. The Class I/III and Level (A) recommendations were homogenous among LMICs. The quality and quantity of stroke prevention guidelines in LMICs are less than those of HICs and need to be significantly improved upon.


Prevalence and distribution of unintended pregnancy: the Understanding Fertility Management in Australia National Survey.
Mistimed, unexpected or unwanted pregnancies occur in Australia, despite widespread contraception use. The objective was to estimate prevalence and ascertain modifiable social factors for prevention of unintended pregnancy. National population-based survey of women and men aged 18-51 years recruited from a random sample of electors on the Australian Electoral Roll in 2013. Data were weighted to reduce non-response bias. Factors associated with unintended pregnancy were identified in multivariable analyses. Data from 2,235 completed questionnaires were analysed (Women: 69%; Men: 31%). Of those ever pregnant or partner in pregnancy (59%), 40% had experienced an unintended pregnancy. Adjusting for other risks, ever having experienced sexual coercion (AOR, 95%CI=Women 1.948; 1.458-2.601; Men 1.657, 1.014-2.708); socioeconomic disadvantage (AOR, 95%CI=Women 1.808, 1.373, 2.381; Men 1.360, 1.004-1.841), living in a rural area (AOR, 95%CI=Women 1.403, 1.056-1.864; Men 1.583, 1.161-2.159), and for men being born overseas (AOR, 95%CI 1.989, 1.317-3.002) were significantly associated with unintended pregnancy. Experiences of sexual coercion, social disadvantage, rural residence and overseas birth are independently associated with unintended pregnancy in Australia. Public health policy and health service initiatives should prioritise prevention of sexual coercion, reduction of social inequality and reduction of geographic inequality for those in rural areas.


Cell regulations of the cerebrospinal fluid in diseases of the central nervous system.
After a survey of the composition and the possibilities of the differentiation of the liquor cytogram, the author reports upon the reaction types of the cerebrospinal fluid. Following the functional mechanisms of the cerebrospinal fluid cells (phagocytosis, digestion, thesaurismosis, formation of antibodies) are to be mentioned.


DNA microarrays for malaria.
DNA microarrays are a powerful tool for the analysis of RNA and DNA composition on a whole-genome scale. The first applications of this technology in parasitology are in place. This review examines the various approaches to Plasmodium transcript-profiling that are being adopted using DNA microarray analysis and discusses additional strategies for obtaining and collating information relevant to the search for drug and vaccine candidates in malaria.