Primary Fallopian Tube Carcinoma: A Case Report and Literature Review.
Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis.


Taenia saginata: an unusual cause of post-appendectomy faecal fistula.
Post-appendectomy faecal fistula is a rare surgical complication, associated with significant morbidity. Taenia saginata infestation is one of the most common cestode infestation in the gastrointestinal tract. It makes many complications as obstruction, perforation, anastomotic leakage or appendicular stump dehiscence. The objective of our study is to report a very rare case of post appendectomy faecal fistula caused by taenia saginata infestation and was successfully treated conservatively.


Functional characterization of SDF-1 proximal promoter.
Stromal-cell derived factor 1 (SDF1) is a CXC chemokine that binds and signals through the CXCR4 receptor, playing an essential role in embryonic B lymphopoiesis, myelopoiesis and organogenesis. The CXCR4/SDF1 pathway is associated with several pathologies. CXCR4 serves as a fusion cofactor for lymphotropic strains of human immunodeficiency virus type 1 and SDF1 inhibits viral entry. Moreover, recent works suggest an important role for SDF1 in metastasis progression and autoimmune diseases such as rheumatoid arthritis. To understand the molecular mechanisms that regulate SDF1 expression, we have cloned and functionally analysed its 5' flanking regulatory region. An SDF1-promoter luciferase construct showed high levels of reporter gene activity in transient transfection experiments. DNase I footprinting analysis revealed that the proximal promoter was occupied by six putative Sp1-binding motifs. Binding of Sp1 to the promoter was confirmed by electrophoretic mobility shift assay, and its importance in SDF1 gene expression verified by in vitro mutagenesis. Particularly, mutation of an Sp1 motif located between -57 and -39 upstream of the main transcription start-site resulted in a marked reduction in promoter activity. It has been shown that the SDF1 expression could be induced by mitogenic stimuli, X-ray radiation or treatment with IL1beta, depending on cell environment. We have analysed the effect of these stimuli on SDF1 promoter transactivation in three different cell lines. Phorbol myristated acetate plus ionomycin increased promoter activity in U373 and LC5 but repressed it in MS5 cells. On the contrary, gamma irradiation promoted SDF1 transcription in MS5 cells but not in the other cell lines. Interferon-gamma acted as a transcriptional repressor in U373 and LC5 but not in MS5 cells. Finally, IL1beta functions as mild activator only in U373 cells. The present study demonstrates that these stimuli mediate SDF1 production through promoter activation in a cell-specific manner.


Are two interventions worse than none? Joint primary and secondary prevention of eating disorders in college females.
Prevention programs for eating disorders attempt to simultaneously prevent new cases from arising (primary prevention) and encourage students who already have symptoms to seek early treatment (secondary prevention), even though ideal strategies for these 2 types of prevention may be incompatible with each other. In the present study, an eating disorder prevention program was evaluated in a simple of female college freshmen. In the intervention, classmates who had recovered from eating disorders described their experiences and provided information about eating disorders. At follow-up, intervention participants had slightly more symptoms of eating disorders than did controls. The program may have been ineffective in preventing eating disorders because by reducing the stigma of these disorders (to encourage students with problems to seek help), the program may have inadvertently normalized them.


Structure-Based Lead Optimization of Enterovirus D68 2A Protease Inhibitors.
Enterovirus D68 (EV-D68) virus is a nonpolio enterovirus that typically causes respiratory illness and, in severe cases, can lead to paralysis and death in children. There is currently no vaccine or antiviral for EV-D68. We previously discovered the viral 2A protease (2Apro) as a viable antiviral drug target and identified telaprevir as a 2Apro inhibitor. 2Apro is a viral cysteine protease that cleaves the viral VP1-2A polyprotein junction. In this study, we report the X-ray crystal structures of EV-D68 2Apro, wild-type, and the C107A mutant and the structure-based lead optimization of telaprevir. Guided by the X-ray crystal structure, we predicted the binding pose of telaprevir in 2Apro using molecular dynamics simulations. We then utilized this model to inform structure-based optimization of the telaprevir's reactive warhead and P1-P4 substitutions. These efforts led to the discovery of 2Apro inhibitors with improved antiviral activity than telaprevir. These compounds represent promising lead compounds for further development as EV-D68 antivirals.


Media and education of the consumer.
The landscape has changed in how consumers get their health information. A shift to the Internet and social media are now the way many consumers obtain their health and medical information. In addition, the highly complex information in medicine and science separates health journalism from other forms of journalism. In this article, the question of the role of media in educating consumers is examined. It is clear that knowledge translation is complex and begs the cooperation of scientists and journalists alike.


RSC Advances Outstanding Student Paper Awards 2022.
We are delighted to announce the winners for the RSC Advances Outstanding Student Paper Awards 2022. These awards recognise outstanding work published in the journal, for which a substantial component of the research was conducted by a student.


Coffin-Siris syndrome with the rarest constellation of congenital cardiac defects: A case report with review of literature.
We report a case of type-A Coffin-Siris syndrome (CSS) with a unique constellation of congenital heart defects. A 17-year-old Indian boy was referred to our hospital for central cyanosis with features of right heart failure. The cardiac abnormalities included biventricular outflow tract obstruction, small atrial septal defect (ASD), subaortic ventricular septal defect, drainage of left superior venacava to left atrial appendage, and aortic arch anomaly. Patient underwent successful right ventricular infundibular resection, subaortic membrane resection, closure of atrial and ventricular septal defect, rerouting left superior vena cava to left pulmonary artery and aortic valve replacement.


Angular-resolved photoelectron spectroscopy of superatom orbitals of fullerenes.
Photoelectron angular distributions from both C(60) and C(70) were recorded for low laser intensity femtosecond and picosecond pulses. Rich structure is seen for electron kinetic energies that lie below the photon energy. Strong, broad peaks are observed for photoelectron energies corresponding to single-photon ionization of so-called superatom molecular orbitals (SAMOs). The very simple angular distributions measured for these peaks, the close similarity of the spectra observed from C(60) and C(70), and the comparison with time-dependent density functional theory provide strong support for the SAMO hypothesis.


Metformin use and cervical cancer risk in female patients with type 2 diabetes.
This study evaluated whether metformin may affect the risk of cervical cancer. The reimbursement databases of the Taiwan's National Health Insurance were used. Female patients with type 2 diabetes at an onset age of 25-74 years during 1999-2005 and newly treated with metformin (n=132971, "ever users of metformin") or other antidiabetic drugs (n=6940, "never users of metformin") were followed for at least 6 months until December 31, 2011. The treatment effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Analyses were also conducted in a 1:1 matched pair cohort based on 8 digits of propensity score. Results showed that the respective numbers of incident cervical cancer in ever users and never users were 438 (0.33%) and 38 (0.55%), with respective incidences of 68.29 and 121.38 per 100,000 person-years. The overall hazard ratio suggested a significantly lower risk in metformin users (0.558, 95% confidence intervals: 0.401-0.778). In tertile analyses, the hazard ratios (95% confidence intervals) for the first (<23.0 months), second (23.0-47.9 months) and third (>47.9 months) tertile of cumulative duration were 1.272 (0.904-1.790), 0.523 (0.366-0.747) and 0.109 (0.070-0.172), respectively. Findings were supported by the analyses in the matched cohort. In conclusion, metformin may significantly reduce the risk of cervical cancer, especially when the cumulative duration is more than 2 years.


Scalable procedure for the fragmentation of hydroperoxides mediated by copper and iron tetrafluoroborate salts.
An improved protocol for the formal elimination of propene from organic substrates is reported. This process entails the ozonolytic conversion of an alkene to a methoxy hydroperoxide which undergoes fragmentation mediated by copper and iron. The use of soluble Cu(BF4)2 and Fe(BF4)2 results in reproducible results up to a 100 gram scale.


Pharmacodynamics of a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) on glucose and insulin levels in healthy males.
Recombinant human insulin-like growth factor-I (rhIGF-I) was evaluated in 7 healthy males to determine the pharmacodynamics on glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/h over 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (p > 0.05) from their pre-dose levels. Compared to the saline (control) infusion, glucose levels were statistically lower (p < 0.05) 2 hours into the rhIGF-I infusion, and were suppressed until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. Therefore, suppression of insulin levels may be due to hypoglycemia rather than a direct action of rhIGF-I. This trial demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic or insulin resistant states.


Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.
Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.


Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies.
Two monoclonal antibodies against the p53 protein, PAb 122 and 200-47, were microinjected into mammalian cells as a probe to determine the role of the p53 protein in cell proliferation. PAb 122 recognizes the p53 proteins of mouse and human cells but not of hamster cells, whereas 200-47 recognizes the p53 proteins of mouse and hamster cells but not of human cells. The ability of these antibodies to inhibit serum-stimulated DNA synthesis of cells in culture correlates with their ability to recognize the species-specific antigenic determinants. More important, however, is the observation that microinjected PAb 122 inhibits the transition of Swiss 3T3 cells from G0 to S phase, but has no effect on the progression of these cells from mitosis to the S phase.


From Experimental Technique to Clinical Practice: Which Pathway in Transplant Surgery?
The question of whether a medical procedure is to be considered experimental or routine practice has enormous practical implications. In transplant surgery, as compared with pharmacologic clinical trials, the transition from experimental procedure to normal care is far from clear cut. Clinical trials comprise 4 well-established phases of evaluation going from phase I, aimed at assessing safety and identifying side effects in a few healthy volunteers, to phase IV, which involves entire populations and is aimed at long-term postmarketing surveillance. In transplant surgery, technical progress and experimentation follow more atypical and individual routes. As compared with pharmacologic research, the decision about "routine practice readiness" of a surgical procedure does not rely on a standardized formal act but rather on experts' capacity to find a consensus based on best practices and on ad-hoc criteria as well. Independent assessment by a panel of experts and oversight by an institutional review board are key to facilitating meaningful protection of transplant recipients and allowing the research to go forward. The framework of the human subjects protection regulations should also consider the transplant of organs that have previously been part of a research project.


Childhood trauma and substance use underlying psychosis: a systematic review.
Background: Schizophrenia spectrum disorders (SSD) are mental diseases caused by a combination of genetic susceptibility and a number of environmental factors. Among these factors, the role of traumatic events suffered in childhood, as well as that of substance use, have been of particular research interest. Objectives: To conduct a systematic review to clarify whether there is an interaction between childhood trauma and substance use related to the diagnosis or symptoms of SSD. It was also the objective of this review to collate the associations that may exist between the three variables of the study (trauma, substance use and psychosis). Methods: We conducted a systematic search resulting in 240 articles. We considered all of the original articles that explored childhood trauma and substance use in patients suffering from SSD. Results: Twenty-three articles were selected for this review. Several of the reviewed papers found associations between childhood trauma and substance use with SSD, as well as interactions between trauma and drug use on SSD. Conclusions: The results suggest that childhood trauma and substance use may be present at the basis of psychosis. This double hit on the pathogenesis could have clinical implications, since each of these impacts could be considered a window of opportunity for the primary prevention of SSD.


Needle core length in sextant biopsy influences prostate cancer detection rate.
Prostate cancer detection in biopsies increases with the number of sites and total tissue sampled. Its dependence on needle core fragment length is uncertain. We surveyed two consecutive series of sextant needle biopsies from two practices in 1998 to 2000: 251 patients from Pennsylvania (group P) and 1596 from Virginia (group V). We tabulated the gross needle core lengths per sextant site and classified the diagnoses as benign or into four nonbenign categories: high-grade prostatic intraepithelial neoplasia; atypical small acinar proliferation, suspicious; atypical small acinar proliferation, suspicious plus high-grade prostatic intraepithelial neoplasia; and cancer. Logistic regression analysis was used to correlate cancer or a nonbenign diagnosis with the total length (sum of six sites) and, after excluding the sites with more than one core, with the length per single core, and the anatomic site of origin (apex, mid-gland, base). The mean total tissue length sampled was 108 +/- 27 mm (range 30 to 275) in group P and 81 +/- 22 mm (range 30 to 228) in group V. Sextant sites with a single core contained a mean of 12.8 +/- 3.5 mm tissue, with a 3.6-fold variation among the middle 95%. Group V core lengths at the apex averaged 11.8 mm, shorter (P = 0.0001) than mid (13.3 mm) or base (12.7 mm). A predictive value of longer length for a nonbenign diagnosis was noted in four of six sextants (P <0.04), with trend strongest at the apex, for which detection was influenced by abnormal digital rectal examination (P = 0.02) or ultrasound (P = 0.04) findings. The length of single cores sampled by sextant biopsy can vary more than 3.6-fold and represents a quality assurance consideration. The effect of length on cancer or nonbenign detection was maximal at the prostatic apex where the cores were shortest.


Transfusion of endothelial cells with lentivirus-mediated expression of fas ligand prolonged survival of rat liver allograft.
Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect liver allograft from acute rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL. Based on the lenti-rFasl/puro expression system, constructs were designed that allowed endothelial cell-specific and continual expression of FasL. Endothelial cells with expression of FasL or viruses recombinant with FasL gene were transfused into portal vein of recipient rats during liver transplant surgery. Comparing groups of rats after liver transplant surgery using regular dose of FK506 and with no other treatment, we observed the aspartate aminotransferase and BIL value and survival of four groups of rat recipients. Values of AST and BIL in the cell and virus transfusion groups were between FK506 and contrast groups. The survival of cell and virus transfusion groups were longer than contrast group and shorter than FK506 group. This in vitro model shows that endothelial cells with expression of FasL or viruses recombinant with FasL gene transfusion can preserve liver function and prolong the survival time of liver allografts.


Social condition affects hormone secretion and exploratory behavior in rats.
Studies of behavior, endocrinology and physiology have described experiments in which animals housed in groups or in isolation were normally tested individually. The isolation of the animal from its group for testing is perhaps the most common situation used today in experimental procedures, i.e., there is no consideration of the acute stress which occurs when the animal is submitted to a situation different from that it is normally accustomed to, i.e., group living. In the present study, we used 90 male 120-day-old rats (Rattus norvegicus) divided into 5 groups of 18 animals, which were housed 3 per cage, in a total of 6 cages. The animals were tested individually or with their groups for exploratory behavior. Hormones were determined by radioimmunoassay using specific kits. The results showed statistically significant differences between testing conditions in terms of behavior and of adrenocorticotrophic hormone (ACTH: from 116.8 +/- 15.27 to 88.77 +/- 18.74 when in group and to 159.6 +/- 11.53 pg/ml when isolated), corticosterone (from 561.01 +/- 77.04 to 1036.47 +/- 79.81 when in group and to 784.71 +/- 55.88 ng/ml when isolated), luteinizing hormone (from 0.84 +/- 0.09 to 0.58 +/- 0.05 when in group and to 0.52 +/- 0.06 ng/ml when isolated) and prolactin (from 5.18 +/- 0.33 to 9.37 +/- 0.96 when in group and to 10.18 +/- 1.23 ng/ml when isolated) secretion, but not in terms of follicle-stimulating hormone or testosterone secretion. The most important feature observed was that in each cage there was one animal with higher ACTH levels than the other two; furthermore, the exploratory behavior of this animal was different, indicating the occurrence of almost constant higher vigilance in this animal (latency to leave the den in group: 99.17 +/- 34.95 and isolated: 675.3 +/- 145.3 s). The data indicate that in each group there is an animal in a peculiar situation and its behavior can be detected by ACTH determination in addition to behavioral performance.


Normal two-dimensional gel electrophoresis of alpha-2-macroglobulin in cystic fibrosis.
Some studies have suggested that a mutant form of alpha-2-macroglobulin (alpha-2-M) could be the primary defect in cystic fibrosis (CF). To test for the presence of charge change amino acid substitutions, alpha-2-M was examined by two-dimensional gel electrophoresis following complete denaturation of the proteins. The pattern of nine charge isomers observed was the same in homozygous, heterozygous, and normal individuals.


Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon.
Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease.


Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment.
In the normal microvasculature, caveolin-1, the structural protein of caveolae, modulates transcytosis and paracellular permeability. Here, we used caveolin-1-deficient mice (Cav(-/-)) to track the potential active roles of caveolin-1 down-modulation in the regulation of vascular permeability and morphogenesis in tumors. In B16 melanoma-bearing Cav(-/-) mice, we found that fibrinogen accumulated in early-stage tumors to a larger extent than in wild-type animals. These results were confirmed by the observations of a net elevation of the interstitial fluid pressure and a relative deficit in albumin extravasation in Cav(-/-) tumors (versus healthy tissues). Immunostaining analyses of Cav(-/-) tumor sections further revealed a higher density of CD31-positive vascular structures and a dramatic deficit in alpha-smooth muscle actin-stained mural cells. The increase in blood plasma volume in Cav(-/-) tumors was confirmed by dynamic contrast enhanced-magnetic resonance imaging and found to be associated with a more rapid tumor growth. Finally, an in vitro wound test and the aorta ring assay revealed that silencing caveolin expression could directly impair the migration and the outgrowth of smooth muscle cells/pericytes, particularly in response to platelet-derived growth factor. In conclusion, a decrease in caveolin abundance, by promoting angiogenesis and preventing its termination by mural cell recruitment, appears as an important control point for the formation of new tumor blood vessels. Caveolin-1 therefore has the potential to be a marker of tumor vasculature maturity that may help adjusting anticancer therapies.


Double contour of the lens capsule edges after continuous curvilinear capsulorhexis.
After curvilinear capsulorhexis in cataract surgery often a double-ring shape of the remaining capsular margins can be observed. In order to better understand this phenomenon we performed a histological study of excised capsules after continuous curvilinear capsulorhexis. Ten anterior capsular specimens from cases with double-ring structure of the capsular margins after continuous curvilinear capsulorhexis (D-group) were examined light microscopically and compared with 10 normal cases (N-group) and 10 cases with pseudoexfoliation (P-group). Three cases from each group were also examined electron microscopically. A characteristic step formation in the capsular edges and in addition horizontal capsular splits in the border zone between the zonular lamella of the anterior capsule and the capsule proper could be demonstrated histologically in the D-group. There seems to be a weak point of the capsular tissue in the border zone between zonular lamella of the lens and the capsule proper. The superficial splits that we found histologically in this region might be a precursor or forme fruste of true exfoliation. The outward-directed traction force exerted by the zonular fibers seems to lead to further disruption in this weakened layer of the lens capsule during capsulorhexis, producing a double-ring contour of the capsular margins.


Decreased Temperature Sensitivity of Vestigial Gene Expression in Temperate Populations of Drosophilamelanogaster.
Drosophila melanogaster recently spread from its tropical origin in Africa and became a cosmopolitan species that has adapted to a wide range of different thermal environments, including temperate climates. An important limiting factor of temperate climates has probably been their low and varying temperatures. The transcriptional output of genes can vary across temperatures, which might have been detrimental while settling in temperate environments. The reduction of temperature-sensitive expression of functionally important genes to ensure consistent levels of gene expression might have been relevant while adapting to such environments. In this study, we focus on the gene vestigial (vg) whose product is a key factor in wing development. We provide evidence that temperature-sensitivity of vg has been buffered in populations from temperate climates. We investigated temperature-sensitivity of vg gene expression in six natural populations, including four temperate populations (three from Europe and one from high-altitude Africa), and two tropical populations from the ancestral species range. All temperate populations exhibited a lower degree of temperature-induced expression plasticity than the tropical populations.


Stages of xylene transforming during carbon particle synthesis.
Xylene is one of the materials that could be used for synthesis of different carbon nanoparticles including perfect carbon spheres with diameters of 1 to 8 microm and ellipsoids. Its changes in the course of the pyrolytic process in a hermetically sealed stainless steal container have been examined by stopping the process at different stage of temperature treatment from 100 degrees C to 600 degrees C. The prepared material is in a liquid phase up to 400 degrees C and its relative weight and optical transmittance changes have been measured. The origins of these changes are traced to solid micro and nanoparticles and their morphology, which was studied by Scanning (SEM) and Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), Electron Probe X-ray Micro Analysis and Energy Dispersive X-ray Spectrometry (EDS), and Fourier Transform Infrared Spectroscopy (FTIR).


Takayasu's arteritis and its role in causing renal artery stenosis.
Takayasu's arteritis is a systemic vasculitis that involves medium- and large-sized arteries. Renal artery involvement is a potential manifestation of TA that occurs in 60% of the patients in India and the Far East. This manifestation can lead to renal failure and/or renovascular hypertension. Renovascular hypertension is generally resistant to medical therapy and often requires additional invasive management strategies, such as angioplasty or surgical bypass. In this review, we present the epidemiology, clinical manifestations, diagnosis and treatment of Takayasu's arteritis with particular emphasis on renal artery stenosis. The aim is to increase the awareness of this condition among clinicians because early diagnosis and the timely introduction of treatment can lead to improved outcomes in this poorly understood clinical enigma.


A novel method of assessing clinical reasoning in surgical residents.
At present, surgical educators can readily assess knowledge with multiple-choice examinations, and inanimate models can be used to assess technical skills. Clinical judgment and reasoning are indispensable skills used by expert surgeons to solve ill-defined problems encountered in the emergency department, clinic, and operating room. The Script Concordance Test, a new tool of clinical reasoning assessment, can test the elaborated networks of knowledge that experienced surgeons develop over the years. It allows for multiple different approaches to the same problem and could be developed as both a formative and summative assessment tool in general surgery residency programs. This article explores the theoretical and practical aspects of the Script Concordance Test.


Role and outcome of surgery for pulmonary tuberculosis.
The need and outcome of surgical intervention in patients with pulmonary tuberculosis were assessed retrospectively. Between 1993 and 2003, 72 major surgical procedures were performed in 57 patients with pulmonary tuberculosis. There were 44 males and 13 females with a mean age of 34 years. Indications for surgery were: trapped lung in 18 (31.6%), multidrug-resistant tuberculosis in 10 (17.5%), aspergilloma in 10 (17.5%), destroyed lung in 5 (8.8%), massive hemoptysis in 4 (7%), bronchopleural fistula in 3 (5.3%), persistent cavity in 2 (3.5%), and undiagnosed nodule in 5 (8.8%) patients. The most common procedure was lobectomy (31.9%). Other procedures included decortication, wedge resection, pneumonectomy, segmentectomy, and myoplasty. There were 28 complications in 18 patients, including prolonged air leak in 12 (21.1%), residual space in 7 (12.3%), empyema in 5 (8.8%), hematoma in 2 (3.5%), chylothorax and bronchopleural fistula in 1 (1.8%) each. There was no operative death, but one patient died from sepsis late in the follow-up period (mortality, 1.8%). As morbidity and mortality rates are acceptable, surgical intervention can be considered safe and effective in patients with pulmonary tuberculosis.


Curanderismo and Latino views of disease and curing.
Curanderismo is a diverse folk healing system of Latin America. Eight major philosophical premises underlie a coherent curing world view of Latino patients: disease or illness may follow (1) strong emotional states (such as rage, fear, envy or mourning of painful loss) or (2) being out of balance or harmony with one's environment; (3) a patient is often the innocent victim of malevolent forces; (4) the soul may become separated from the body (loss of soul); (5) cure requires the participation of the entire family; (6) the natural world is not always distinguishable from the supernatural; (7) sickness often serves the social function, through increased attention and rallying of the family around a patient, of reestablishing a sense of belonging (resocialization) and (8) Latinos respond better to an open interaction with their healer. These nuclear ideas or attitudes about health, illness and care are culturally patterned and are both conscious and unconscious (implicit). Moreover, expectations of the nature of the patient-healer relationship have implications for medical practice in general and psychotherapy in particular.


Safety evaluation of the food enzyme β-galactosidase from the non-genetically modified Aspergillus oryzae strain GL 470.
The food enzyme β-galactosidase (β-d-galactoside galactohydrolase; EC 22.214.171.124) is produced with the Aspergillus oryzae strain GL 470 by Shin Nihon Chemical Co., Ltd. The food enzyme is free from viable cells of the production organism. It is intended to be used in five food manufacturing processes; lactose hydrolysis in milk processing, production of fermented milk products, whey processing, manufacture of enzyme-modified dairy ingredients and in the manufacture of galacto-oligosaccharides. Dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be up to 1.388 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of repeated dose 90-day oral toxicity studies in rats. The Panel identified a no observed adverse effect level of 7,000 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, results in a margin of exposure of at least 5,043. A search for similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel concluded that, under the intended conditions of use, the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided and considering the most recent complete toxicological data set, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.


Corrigendum: Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Ralstonia solanacearum Phylotype I Mulberry Strains in China.
[This corrects the article on p. 76 in vol. 8, PMID: 28197157.].


T cell maturation: thymocyte and thymus migrant subpopulations defined with monoclonal antibodies to MHC region antigens.
The maturation sequences of thymocytes is known to some extent: A generative layer of subcapsular large lymphoblasts gives rise to a major population of small cortical thymocytes and a minor population of midsize medullary thymocytes. The relative contribution of these three populations to the peripheral T cell populations is not yet known. In this study, subcapsular lymphoblasts, cortical small cells, medullary cells, and thymic emigrant cells have all been analyzed by immunofluorescence for expression of the antigens H-2D, I-A, H-2K, and TL. H-2D is expressed brightly on all subcapsular large cells, dimly on cortical small cells, and brightly on all migrants, cortisone-resistant thymocytes (CRT), and peripheral T cells. I-A can be detected at low levels on 30 to 50% of cells in all the thymic subpopulations, and on 30 to 50% of migrants and peripheral T cells. Fifty to 80% of small cortical cells do not express detectable H-2K, but all the other subpopulations, both inside and outside the thymus, stain uniformly quite brightly. TL3 is expressed on 70 to 80% of subcapsular and cortical thymocytes, 30 to 40% of CRT, is undetectable on migrants but can be seen at low levels on 10 to 20% of spleen and lymph node T cells. The possibility that some or all of these antigens represent stable markers of separate lineages rather than unstable, stage-specific markers is discussed.


PCBs in school-persistent chemicals, persistent problems.
The issue of polychlorinated biphenyls (PCB) exposures resulting from occupancy of PCB-contaminated buildings is not new, but the contribution of building materials to that contamination is largely unrecognized. A rapidly emerging base of evidence shows that PCBs can be widely found in caulking and paint in masonry buildings constructed or renovated from about 1950 to the late 1970s. These materials can cause extensive PCB contamination of the building interiors and surrounding soil, and people who teach, live, or attend school in these buildings can have elevated serum PCB levels. The potential risk associated with this source of PCB exposure is not known; however, it is worth noting that the specific PCB congeners found at high levels in the building environments, and in biological samples from the occupants, include some that are suspected of being potent neurotoxins. The U. S. Environmental Protection Agency (EPA) is moving to address this issue in schools; however, the costs of remediating contaminated buildings will pose a formidable obstacle to most school districts.


EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer.
RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue. Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing. In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy. PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 °C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 °C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks. Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.


Serotonin and melatonin secretion and metabolism in patients with liver cirrhosis.
Hepatic encephalopathy is one of the symptoms of liver failure. The exact causes of encephalopathy are complex and still unclear. Apart from elevated blood ammonia levels, the role of numerous other factors is being considered. The aim of the study was to determine the serum level of serotonin and melatonin and the urinary excretion of their metabolites (5-hydroxyindoleacetic acid [5-HIAA] and 6-sulfatoxymelatonin [6-HMS]) in patients with various stages of liver cirrhosis. The study comprised 75 patients with alcohol-induced liver cirrhosis and 25 healthy subjects (control group). Based on the Child-Pugh classification, 3 groups of 25 patients each were distinguished - group A, B, and C with grade A, B, and C of liver failure, respectively. Blood samples were drawn at fasting at 9 a.m., and 24-hour urine collection was performed. Immunoenzymatic assays were used to determine serum melatonin and serotonin levels as well as urine 5-HIAA and 6-HMS concentrations. Serum serotonin levels were 159.8 ± 23.1 ng/ml in controls, 179.3 ± 21.1 ng/ml in group A (P >0.05), 143.2 ± 22.8 ng/ml in group B (P >0.05), and 114.5 ± 37.6 ng/ml in group C (P <0.01). Serum melatonin levels were 10.6 ± 1.7 in controls, 31.2 ± 9.8 pg/ml in group A (P <0.01), 49.8 ± 12.2 pg/ml in group B (P <0.001), and 94.8 ± 22.6 pg/ml in group C (P <0.001). Urinary 5-HIAA excretion was 5.9 ± 2.1 mg/24 h in controls, 5.9 ± 1.9 mg/24 h in group A (P >0.05), 4.8 ± 1.2 mg/24 h in group B (P >0.05), and 4.6 ± 1.4 mg/24 h in group C (P <0.05). Urinary 6-HMS excretion was 26.6 ± 15.1 μg/24 h in controls, 23.2 ± 7.9 μg/24 h in group A (P >0.05), 18.3 ± 10.6 μg/24 h in group B (P >0.05), and 6.5 ± 3.6 μg/24 h in group C (P <0.001). Disturbances in serotonin and melatonin homeostasis observed in patients with liver cirrhosis may be associated with advanced encopaholopathy.


[Gabapentin in children and adolescents with epilepsy].
We analyze the studies published on gabapentin (GBP) in children and adolescents with epilepsy, both clinical studies, in which it is used to treat patients with partial seizures refractory to treatment with other drugs, and in other studies of its use as monotherapy. We report the results of a multicentric observational study carried out in Spain using GBP as monotherapy for 52 adolescents with partial seizures with no previous treatment (32) or as a second alternative treatment (20). We showed evident clinical efficacy, with a reduction of >50% in the frequency of seizures in 79% of the cases and abolition of seizures in 60%, after six months of treatment with GBP. At the same time the drug is very well tolerated, with adverse effects in 7.7% of cases. The drug was only suspended on account of adverse effects in one patient (1.9%). Simultaneously all the basic items of the QOLIE 10 questionnaire were improved after six months of treatment. GBP is an effective drug which is well tolerated by children and adolescents with partial crises, when used in polytherapy or as monotherapy.


Bile acid activation of the gadd153 promoter and of p53-independent apoptosis: relevance to colon cancer.
Bile acids are strongly implicated in the etiology of colon cancer. Bile acids also induce apoptosis, and this action may be a key to understanding their role in colon cancer. However the mechanism of bile acid induction of apoptosis is not known. We present evidence of bile acid activation of the gadd153 promoter (a promoter activated by DNA damaging agents). We also show that bile acid induction of apoptosis is p53-independent. In addition, bile salts were found to induce blebbing preceding the actual morphological onset of apoptosis, which indicates early cytoskeletal alterations.


A case report: upgrade to cardiac resynchronization therapy with a blocked persistent left-sided superior vena cava.
Pacemaker-induced cardiomyopathy (PICM) can occur in up to 9% of patients having a pacemaker. Pacemaker-induced cardiomyopathy can be treated by upgrade to a biventricular pacemaker with a left ventricular (LV) lead implantation. The procedure can be technically challenging in patients with persistent left-sided superior vena cava (PLSVC). We report the case of a 72-year-old gentleman with a PLSVC, who had a dual-chamber pacemaker implanted 15 years ago for complete heart block. After 12 years of good health, the gentleman developed breathlessness due to PICM. At upgrade to biventricular pacemaker, his coronary sinus was found to be occluded and a collateral branch was used to successfully position an LV lead. Marked clinical improvement was seen before representation with syncope after 2 years due to simultaneous failure of both LV and right ventricular leads. Subsequently, a right-sided de novo biventricular pacemaker was implanted. In this instance, the PLSVC was beneficial because it isolated the existing leads from the new implant, thereby reducing the risk of SVC obstruction. Although implantation of pacemaker leads through a PLSVC constitutes a challenging procedure due to manoeuvring difficulties of the pacing leads into the cardiac chambers, in this particular case, the presence of PLSVC was beneficial because it meant that no leads were present in the true SVC, reducing the risk of occlusion and avoiding the need for lead extraction.


Persistent arthritis in Borrelia burgdorferi-infected HLA-DR4-positive CD28-negative mice post-antibiotic treatment.
The immunologic events that lead to persistent joint inflammation in certain patients with Lyme arthritis post-antibiotic treatment have been elusive so far. The prevalence of this condition is highest in individuals with rheumatoid arthritis-associated HLA-DR alleles. This study was undertaken to generate a murine model with persistent arthritis post-antibiotic treatment. We have previously shown that CD28(-/-) mice develop intermittent monarticular Lyme arthritis that is responsive to antibiotics. Since there seems to be a link in humans between persistent arthritic manifestations post-antibiotic treatment and the HLA-DR4 allele, we generated DR4+/+CD28(-/-)MHCII(-/-) mice, infected them with Borrelia burgdorferi, and subsequently treated them with antibiotics. Thirty-eight percent of the B burgdorferi-infected DR4+/+CD28(-/-)MHCII(-/-) mice, but none of the B burgdorferi-infected CD28(-/-)MHCII(-/-) mice, remained arthritic post-antibiotic treatment. A significant fraction (36%) of these mice, but none of the mice in which arthritis resolved, had serum antibodies to outer surface protein A of B burgdorferi. After abrogation of active B burgdorferi infection, the inflammatory reaction in mice with persistent joint inflammation was restricted to the joints, since their draining lymph nodes were no longer enlarged. Increased CD20 and interferon-gamma messenger RNA expression in the inflamed joints of these mice suggested a possible role of B cells and inflammatory cytokines in the pathogenesis of persistent arthritis post-antibiotic treatment. The establishment of this murine model allows, for the first time, the elucidation of the immunologic events that lead to persistent Lyme arthritis post-antibiotic therapy in genetically susceptible individuals.


Hepatitis A incidence and hepatitis a vaccination among American Indians and Alaska Natives, 1990-2001.
We assessed the effect on trends in hepatitis A incidence of the 1996 recommendation for routine hepatitis A vaccination of American Indian/Alaska Native (AIAN) children. We examined trends in hepatitis A incidence among AIAN peoples during 1990-2001 and vaccination coverage levels among children on the largest American Indian reservation. Hepatitis A rates among AIANs declined 20-fold during 1997-2001. Declines in hepatitis A incidence occurred among AIANs in reservation and metropolitan areas. Among 1956 children living on the Navajo Nation whose medical records were reviewed, 1508 (77.1%) had received at least one dose of hepatitis A vaccine, and 1020 (52.1%) had completed the vaccine series. Hepatitis A rates among AIAN peoples have declined dramatically coincident with implementation of routine hepatitis A vaccination of AIAN children.


Apical and basal neurones isolated from the mouse vomeronasal organ differ for voltage-dependent currents.
The mammalian vomeronasal organ (VNO) contains specialized neurones that transduce the chemical information related to pheromones into discharge of action potentials to the brain. Molecular and biochemical studies have shown that specific components of the pheromonal transduction systems are segregated into two distinct subsets of vomeronasal neurones: apical neurones and basal neurones. However, it is still unknown whether these neuronal subsets also differ in other functional characteristics, such as their membrane properties. We addressed this issue by studying the electrophysiological properties of vomeronasal neurones isolated from mouse VNO. We used the patch-clamp technique to examine both the passive membrane properties and the voltage-gated Na+, K+ and Ca2+ currents. Apical neurones were distinguished from basal ones by the length of their dendrites and by their distinct immunoreactivity for the putative pheromone receptor V2R2. The analysis of passive properties revealed that there were no significant differences between the two neuronal subsets. Also, apical neurones were similar to basal neurones in their biophysical and pharmacological properties of voltage-gated Na+ and K+ currents. However, we found that the density of Na+ currents was about 2-3 times greater in apical neurones than in basal neurones. Consistently, in situ hybridization analysis revealed a higher expression of the Na+ channel subtype III in apical neurones than in basal ones. In contrast, basal neurones were endowed with Ca2+ currents (T-type) of greater magnitude than apical neurones. Our findings indicate that apical and basal neurones in the VNO exhibit distinct electrical properties. This might have a profound effect on the sensory processes occurring in the VNO during pheromone detection.


Diminished hepatic expression of the HNF-6 transcription factor during bile duct obstruction.
Hepatocyte nuclear factor 6 (HNF-6) is a member of the one cut family of transcription factors and potentially regulates expression of numerous target genes important for hepatocyte function. In the liver, HNF-6 is expressed not only in hepatocytes, but also in biliary epithelial cells (BEC). To evaluate the in vivo function of HNF-6, we examined the hepatic expression pattern of HNF-6 messenger RNA (mRNA) and protein after bile duct ligation (BDL)-mediated liver injury. We found that HNF-6 protein levels in BEC and hepatocytes were diminished within 15 hours of BDL injury and remained suppressed through the fifth day of injury. The onset of BEC proliferation in response to bile duct obstruction was associated with diminished HNF-6 protein levels. To maintain hepatic HNF-6 protein levels during BDL liver injury, we used mouse tail vein injections with recombinant adenovirus expressing HNF-6 complementary DNA (cDNA) (AdH6). We found that maintaining hepatic HNF-6 levels with AdH6 infection resulted in significant decreases in BEC proliferation at 15 and 24 hours after biliary obstruction compared with adenovirus control. Our results showed that HNF-6 expression is diminished in BEC and hepatocytes and that maintaining hepatic HNF-6 expression hinders the normal biliary proliferative response to bile duct injury. This suggests that diminished hepatic HNF-6 levels are required for repair in response to biliary injury and that it regulates expression of genes that possess differentiation-specific function that are inhibitory to proliferation. In conclusion, we propose a biologic role for diminished HNF-6 protein levels in bile duct disease.


Ruminiclostridium 5, Parabacteroides distasonis, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms.
Chronic disruption of rhythms (CDR) impacts sleep and can result in circadian misalignment of physiological systems which, in turn, is associated with increased disease risk. Exposure to repeated or severe stressors also disturbs sleep and diurnal rhythms. Prebiotic nutrients produce favorable changes in gut microbial ecology, the gut metabolome, and reduce several negative impacts of acute severe stressor exposure, including disturbed sleep, core body temperature rhythmicity, and gut microbial dysbiosis. In light of previous compelling evidence that prebiotic diet broadly reduces negative impacts of acute, severe stressors, we hypothesize that prebiotic diet will also effectively mitigate the negative impacts of chronic disruption of circadian rhythms on physiology and sleep/wake behavior. Male, Sprague Dawley rats were fed diets enriched in prebiotic substrates or calorically matched control chow. After 5 weeks on diet, rats were exposed to CDR (12 h light/dark reversal, weekly for 8 weeks) or remained on undisturbed normal light/dark cycles (NLD). Sleep EEG, core body temperature, and locomotor activity were recorded via biotelemetry in freely moving rats. Fecal samples were collected on experimental days -33, 0 (day of onset of CDR), and 42. Taxonomic identification and relative abundances of gut microbes were measured in fecal samples using 16S rRNA gene sequencing and shotgun metagenomics. Fecal primary, bacterially modified secondary, and conjugated bile acids were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Prebiotic diet produced rapid and stable increases in the relative abundances of Parabacteroides distasonis and Ruminiclostridium 5. Shotgun metagenomics analyses confirmed reliable increases in relative abundances of Parabacteroides distasonis and Clostridium leptum, a member of the Ruminiclostridium genus. Prebiotic diet also modified fecal bile acid profiles; and based on correlational and step-wise regression analyses, Parabacteroides distasonis and Ruminiclostridium 5 were positively associated with each other and negatively associated with secondary and conjugated bile acids. Prebiotic diet, but not CDR, impacted beta diversity. Measures of alpha diversity evenness were decreased by CDR and prebiotic diet prevented that effect. Rats exposed to CDR while eating prebiotic, compared to control diet, more quickly realigned NREM sleep and core body temperature (ClockLab) diurnal rhythms to the altered light/dark cycle. Finally, both cholic acid and Ruminiclostridium 5 prior to CDR were associated with time to realign CBT rhythms to the new light/dark cycle after CDR; whereas both Ruminiclostridium 5 and taurocholic acid prior to CDR were associated with NREM sleep recovery after CDR. These results support our hypothesis and suggest that ingestion of prebiotic substrates is an effective strategy to increase the relative abundance of health promoting microbes, alter the fecal bile acid profile, and facilitate the recovery and realignment of sleep and diurnal rhythms after circadian disruption.


[Recurrent digital fibromatosis in children].
We present two cases of recurrent digital fibromatosis, one of them presented lesions since birth, aun the other one since seven months of age. The first case was treated surgically, with relapses and marked deformities. The second one underwent only biopsy. Histopathologic examination showed active fibroblasts, in whorl disposition, and intracytoplasmic inclusions in both cases. By its natural evolution, we believe that recurrent infantile digital fibromatosis has an initial stage, a tumoral or hyperplastic stage, and finally spontaneous evolution, which explains the fact that it is not found in adults.


Mechanistic aspects of the de-novo synthesis of PCDD/PCDF on model mixtures and MSWI fly ashes using amorphous 12C- and 13C-labeled carbon.
The formation of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) from amorphous 12C- and 13C-labeled carbon was studied on model mixtures and real fly ashes. PCDD/F can either be formed directly (de-novo) from carbon already present in fly ash or step-by-step via condensation of two aromatic rings. Using model mixtures containing 12C- and 13C-labeled carbon in various ratios we observed the formation of the following compound classes: 12C6-PCPh, -PCBz, 13C6-PCPh, -PCBz, 12C12-PCDD/ F, 13C12-PCDD/F, and 12C6 13C6-PCDD/F. By examining the fraction of the mixed PCDD/F (one of the two aromatic ring is composed solely of 12C-atoms while the other contains only 13C-atoms) in the total concentration of PCDD/F, conclusions on the formation of these three ring structures are possible. From the experimental results, it can be concluded that both reaction mechanisms are operative in the formation of PCDD/F from carbon. On fly ashes approximately half of the total amount of PCDD is formed via condensation of de-novo created C6-precursors e.g. chlorophenols, while the remainder is directly released (de-novo) from the carbon i.e., formed from a related C12-structure. However, the condensation of intermediate aromatic C6-precursors is of minor importance in the formation of PCDF. With increasing temperature the relative amount of the 12C6 13C6-PCDD formed by condensation decreases due to the faster evaporation of chlorophenols. At a constant reaction temperature, the ratio of both reaction pathways is hardly influenced by reaction time. In experiments with fly ashes doped with 13C-labeled carbon, this carbon isotope shows a similar reactivity as the native carbon present on the fly ash. Thus, the used amorphous carbons are suitable models for this investigation.


Retropubic prostatectomy for giant benign prostatic hyperplasia.
Giant benign prostatic hyperplasia is a rare pathology of the prostate gland. Here we report the successful removal of the ninth largest prostate ever reported. This 65-year-old patient presented with acute urinary retention secondary to a bulky left prostatic mass identified on pelvic magnetic resonance imaging (MRI). His preoperative prostate-specific antigen (PSA) value was 44 ng/mL; preoperative biopsies were negative for malignancy. Open radical retropubic prostatectomy was performed and the resulting prostatic mass was measured at 13.5 cm x 11.5 cm x 5.2 cm, weighing 708 g including the prostate. The patient tolerated the procedure well. Surgical pathology showed no evidence of malignancy.


Radiation-induced meningiomas involving the orbit.
To review the clinical features and outcomes of patients with radiation-induced meningiomas involving the orbit. Retrospective case series. Eight patients with radiation-induced meningiomas affecting the orbit. Clinical and pathologic data of the patients were reviewed. Age at diagnosis, mean interval between radiation therapy and meningioma diagnosis, tumor recurrence, histologic atypia, and mean follow-up time after initial diagnosis. The mean age at diagnosis was 42 years (range, 21 years to 70 years). The mean interval between radiation therapy and meningioma diagnosis was 26 years (range, 3 years to 54 years). All patients underwent gross total resection or subtotal resection of the meningioma. Five tumors (62.5%) recurred, based on clinical findings and CT imaging. The mean interval between resection of the meningioma and recurrence was 3 years (range, 9 months to 9 years). Three patients (37.5%) had atypical meningiomas. One patient (12.5%) had multiple tumors. The mean follow-up interval was 7 years after initial diagnosis of the meningioma (range, 15 months to 19 years). This series of radiation-induced meningiomas, the first in the ophthalmic literature, illustrates the aggressive nature of this tumor.


Systemic Lupus Erythematosus-associated Acute Acalculous Cholecystitis Successfully Treated by a Corticosteroid Combined with Azathioprine.
A 69-year-old Japanese woman was transferred to our hospital due to pancytopenia with a fever. She had Murphy's sign, and computed tomography showed pleural effusion and a swollen gallbladder without gallstones. We diagnosed her with systemic lupus erythematosus (SLE)-associated acute acalculous cholecystitis (AAC). Partly because her clinical and laboratory findings were not serious enough to warrant immediate surgical intervention, and partly because her poor general condition made her ineligible for surgery, surgical therapy was not selected. Corticosteroid therapy was performed with azathioprine, and the swelling in her gallbladder improved. As a conservative therapy for SLE-associated AAC, corticosteroid therapy combined with azathioprine might be beneficial.


Minimally Invasive LVAD Deactivation in a 65-Year-Old Man with Recurrent Pump Thrombosis and Left Ventricular Recovery.
Pump thrombosis is a dire sequela after left ventricular assist device (LVAD) implantation. Treatment comprises antiplatelet agents, anticoagulants, thrombolytic agents, and pump exchange. Although pump exchange is the definitive therapy, it is also the most invasive, often exposing patients to the risks of repeat sternotomy and cardiopulmonary bypass. In some cases, patients experience left ventricular recovery after LVAD implantation. The optimal strategy surrounding the management of LVADs in patients who have experienced ventricular recovery is unknown; techniques range from total system explantation to partial pump resection. Here, we describe a novel means of LVAD deactivation in a 65-year-old man with recurrent pump thrombosis, via percutaneous outflow graft closure in the cardiac catheterization laboratory. We also review the existing literature on surgical and percutaneous LVAD deactivation techniques.


[Effect of mild hypobaric hypoxia in the preconditioning regime on expression of pCREB and NF-kappaB transcription factors in the rat hippocampus before and after severe hypoxia].
Preconditioning using threefold mild hypobaric hypoxia (HH) is known to increase the tolerance of vulnerable brain neurons to severe hypoxia and other damaging factors. In the present study, the changes of the expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB (cAMP response element binding protein) were studied in the hippocampus of rats preconditioned by mild hypoxia. Using immunocytochemical method, it was demonstrated that HH increased NF-kappaB and phosphorylated CREB (pCREB) immunoreactivity in CA1-CA4 fields of the hippocampus and gyrus dentatus. It also contributed to the up-regulation of the expression of these transcription factors in the hippocampus of preconditioned rats 3-24 h following severe HH. These findings suggest that NF-kappaB and CREB are involved in HH-activated mechanisms of brain tolerance development.


Early changes in myocardial antioxidant enzymes in rats treated with adriamycin.
Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.


Connective tissue reattachment as related to presence or absence of alveolar bone.
The present study was designed to examine if alveolar bone, located adjacent to a root surface deprived of its periodontal ligament and cementum layer, can stimulate the reformation of a connective tissue attachment. The maxillary and mandibular incisors in 3 monkeys were extracted. Immediately after tooth extraction, the buccal root surfaces of the incisors from the left side of the jaws were planed by means of curettes to a level corresponding to half the root length. All teeth were then reimplanted into their original sockets. However, before tooth reimplantation, the buccal alveolar bone plate was removed in 2 of the monkeys to a level corresponding to half the depth of the sockets. The animals were sacrificed 6 months after the reimplantation procedure. The jaws were removed and histological sections of the experimental teeth and adjacent periodontal tissues were produced. The sections were analyzed in the microscope and subjected to histometric measurements. The results demonstrated that, irrespective of the presence or absence of alveolar bone, a fibrous reattachment failed to form on that part of the reimplanted teeth which had been deprived of their periodontal ligament. This indicates that alveolar bone located adjacent to a root surface may have limited influence on the biological conditions which determine whether periodontal healing results in connective tissue reattachment or new attachment.


Intragenomic heterogeneity of 16S rRNA genes causes overestimation of prokaryotic diversity.
Ever since Carl Woese introduced the use of 16S rRNA genes for determining the phylogenetic relationships of prokaryotes, this method has been regarded as the "gold standard" in both microbial phylogeny and ecology studies. However, intragenomic heterogeneity within 16S rRNA genes has been reported in many investigations and is believed to bias the estimation of prokaryotic diversity. In the current study, 2,013 completely sequenced genomes of bacteria and archaea were analyzed and intragenomic heterogeneity was found in 952 genomes (585 species), with 87.5% of the divergence detected being below the 1% level. In particular, some extremophiles (thermophiles and halophiles) were found to harbor highly divergent 16S rRNA genes. Overestimation caused by 16S rRNA gene intragenomic heterogeneity was evaluated at different levels using the full-length and partial 16S rRNA genes usually chosen as targets for pyrosequencing. The result indicates that, at the unique level, full-length 16S rRNA genes can produce an overestimation of as much as 123.7%, while at the 3% level, an overestimation of 12.9% for the V6 region may be introduced. Further analysis showed that intragenomic heterogeneity tends to concentrate in specific positions, with the V1 and V6 regions suffering the most intragenomic heterogeneity and the V4 and V5 regions suffering the least intragenomic heterogeneity in bacteria. This is the most up-to-date overview of the diversity of 16S rRNA genes within prokaryotic genomes. It not only provides general guidance on how much overestimation can be introduced when applying 16S rRNA gene-based methods, due to its intragenomic heterogeneity, but also recommends that, for bacteria, this overestimation be minimized using primers targeting the V4 and V5 regions.


Effect of flashing light from blue light emitting diodes on cell growth and astaxanthin production of Haematococcus pluvialis.
To conserve energy in the production of astaxanthin by the green alga Haematococcus pluvialis, we utilized intermittent flashing light from blue light emitting diodes (LEDs) and investigated the effects of the incident light intensity (2-12 micromol m(-2) s(-1)), duty cycle (17-67%) and frequency (25-200 Hz) of flashing on the cell growth and astaxanthin production. In the above ranges, the final astaxanthin concentration under illumination by flashing light was significantly higher than that obtained under illumination with continuous light at the same incident intensity. For example, flashing light at an incident intensity of 8 micromol m(-2) s(-1) gave the same final astaxanthin concentration that was obtained under continuous light illumination at 12 micromol m(-2) s(-1), thus reducing energy consumption by 1/3. We therefore conclude that flashing light from blue LEDs is a promising illumination method for indoor algal cultivation using photobioreactors.


[Obesity in children: Risk factors and strategies for its prevention in Peru].
The prevalence of overweight and obesity in children and adolescents represents an emerging public health problem in Peru, so it is necessary to be aware of the different risk factors in order to establish suitable and efficient prevention measures. These should contribute to health strategies such as promoting physical activity and a healthy diet to ensure that the infant population reaches adulthood without chronic diseases and with an adequate quality of life.


Recurring Local Tumor Progression After Cryoablation of Renal Cell Carcinoma.
We describe three cases of renal cell carcinoma (RCC) with recurring local tumor progression, i.e., local failure following repeat cryoablation for a locally progressed tumor. A second local progression developed in all cases after cryoablation for the first local progression, despite there being a sufficiently large ice-ball margin. In two cases, the second local progression was treated with microwave ablation and controlled in the follow-up. In one case, a third cryoablation was performed, but a third local progression developed after 12 months. These cases suggest that some RCCs may be refractory to cryoablation. In cases of recurring local progression, switching from cryoablation to another ablation modality may be an alternative.


Effects of deep brain stimulation frequency on bradykinesia of Parkinson's disease.
Deep brain stimulation (DBS) in Parkinson's disease (PD) is frequency-dependent. Past studies of the effect of DBS frequency, however, involved scrutiny of too few frequencies to eliminate risk of undersampling. Also, these studies presented averaged measures across subjects; high intersubject variability makes these measures problematic. In this study, 6 subjects with PD were tested in a drug-minimal state. Following 10 minutes of stimulation at the new frequency, all available frequencies were tested. Hand-opening and hand-closing amplitude and frequency were measured in 3 epochs of 15 seconds each. Multiple frequencies (low and high) resulted in peaks of increased movement amplitudes. Peaks were specific and varied among individuals. No clear relationship between stimulation frequency and movement frequency was discovered. In light of the findings, a wider range of stimulation frequencies should be examined, particularly lower frequencies. Most current theories of PD pathophysiology and DBS mechanisms of action fail to explain results of the kind demonstrated herein.


[Prevention of myoclonus after etomidate using a priming dose].
To investigate the influence of pretreatment with a low dose of etomidate (priming dose) on the incidence of etomidate-induced myoclonus. Prospective randomized double-blind study. Forty six patients ASA physical status I - II, scheduled for abdominal elective surgery, were allocated randomly to receive either pre-treatment 0.03 mg/kg of etomidate (priming group) or placebo (control group). Sixty-seconds after the pre-treatment was injected, anesthesia was induced with etomidate 0.3 mg/kg and 60 seconds later induction was completed with fentanyl (3 microg/kg) and vecuronium (0.1 mg/kg). The occurrence and intensity of myoclonus were graded clinically by a blinded observer as: 0=no myoclonus, 1=mild myoclonus, 2=moderate myoclonus and 3=severe myoclonus. Fisher test exact for qualitative variable and Student t-test for quantitative variables. Demographic data and the average dose of etomidate used during the induction were similar in the 2 groups (0.29+/-0.032 mg/kg in the priming group and 0.30+/-0.029 mg/kg in the control group). Twenty patients (87%) in the control group experienced myoclonic movements whereas only 6 patients (26%) in the control group had such movements (P<0,001). Pretreatment with etomidate (0.03 mg/kg), given 60 seconds before induction of anesthesia, is effective at reducing etomidate-induced myoclonus, without related side-effect.


The current reality of soft tissue sarcomas: advances, controversies, areas for improvement, and promising new treatments.
Introduction: Soft tissue sarcomas (STS) encompass a group of rare and heterogeneous cancers. Rapid evolution in the field justifies a focused critical review of the clinical literature.Areas covered: Important advances, and associated controversies, in managing patients with STS are reviewed by treatment setting, histopathological subtype, and general management considerations. Despite many advances, opportunities remain to improve care to benefit patients. Areas of sarcoma research showing early promise indicate that new treatment development requires a deeper understanding of the biological characteristics of unique histotypes, with a focus on targeting sarcoma-relevant oncogenic driver mechanisms.Expert opinion: Mandatory treatment of sarcoma patients in reference centers represents a simple and cost-effective means of improving survival as the knowledge generated through international collaboration can be implemented sooner to improve patient outcomes. Sarcoma complexity complicates clinical trial designs in both peri-operative and advanced treatment settings. Future trials in front-line therapy in advanced situations should enroll patients based on the goal of therapy - tumor shrinkage or palliation - using appropriate endpoints to evaluate benefit. Global collaboration remains key to identifying the most appropriate patients and concepts to test in well-designed and accessible clinical trials. The sarcoma community shares a common desire that standard treatments will be established based on molecular profiling within the next five to 10 years.


Hormetic Effects of Carbendazim on the Virulence of Botrytis cinerea.
The ascomycete plant-pathogenic fungus Botrytis cinerea infects more than 1,400 plant species worldwide. Stimulatory effects of sublethal doses of fungicides on plant pathogens are of close relevance to disease management. In the present study, stimulatory effects of carbendazim on the virulence of B. cinerea to cucumber plants were investigated. Spraying carbendazim on cucumber plants at 3 to 200 μg/ml had stimulatory effects on the virulence of carbendazim-resistant isolates of B. cinerea and the maximum percent stimulations were 16.7 and 13.5% for isolates HBtom451 and HBstr491, respectively. Preconditioned mycelia (i.e., mycelia grown on potato dextrose agar [PDA] amended with carbendazim at concentrations of 10, 50, or 200 μg/ml) also showed increased virulence, and the maximum percent stimulations for isolates HBtom451 and HBstr491 were 7.9 and 9.5%, respectively. Compared with mycelia grown on PDA without carbendazim, virulence stimulation magnitudes of spraying carbendazim on leaves increased moderately but the concentrations of carbendazim that elicited the maximum stimulation increased 20- and 8-fold for preconditioned isolates HBtom451 and HBstr491, respectively. The time course of infection indicated that virulence stimulation was mediated by a direct stimulation mechanism. Studies of the physiological mechanism for stimulation demonstrated that carbendazim had no significant effects on tolerance to hydrogen peroxide, or on oxalic acid production in B. cinerea. These studies will deepen our understanding of quantitative features of hormetic effects of sublethal doses of fungicides on plant pathogens.


Trends in embolectomy of the extremities: a population-based study.
There is anecdotal evidence that fewer brachial and femoral embolectomies are being carried out. This may be because of the greater use of anticoagulation in patients with atrial fibrillation. The aim of the present study was to assess community-wide temporal trends in embolectomy of the extremities and of warfarin usage. The Western Australian Linked Data System was used to identify cases of extremity embolectomy with a combination of diagnosis (upper or lower limb embolus) and procedure (embolectomy and revascularization) codes. Trends in age-specific and age-standardized rates were assessed over the period 1992-2003. Data regarding warfarin prescriptions were acquired from the Pharmaceutical Benefits Schedule database for the period 2000-2005. One thousand and five patients aged 30 years and more underwent an embolectomy of the extremity during the study period. The age-specific rate of embolectomy increased from 0.78 per 100,000 in the 30- to 49-year-old group to 46.1 per 100,000 for those aged 80 years and more. There was a significant downward trend between 1992 and 2003 (Cuzik's trend test P = 0.015). This pattern was seen for all age groups. Prescriptions for warfarin increased by 50.4% over the period 2000-2005. The rates of embolectomy of the extremity appear to be falling. Although the cause for this trend is not known, one possible explanation is increasing prescription of warfarin.


[Late sequelae in a group of children and adolescents treated for cancer between 1981 and 1986 in Switzerland].
An ever-growing number of children with malignant diseases can today be cured and will have prolonged survival. Their quality of life, which can be altered by a substantial number of late effects of the disease or its treatment, is a prominent field of long-term assessment. In a cross-sectional study based on clinical and paraclinical parameters and covering 59 children and young adults treated between 1981 and 1986 for a childhood malignant disease, we investigated late effects in the long-term survivors. Late effects were found in 36 (61%) of these patients; their spectrum is wide, but most often affected are the CNS and the musculoskeletal system. Two thirds of the patients have mild or moderate and one third severe problems. The frequency of the late effects and the type of problem vary greatly according to the initial diagnosis; our results show a significant difference of severity according to the number of affected systems (p < 0.05). The results of our study match those of other similar reports and confirm the high frequency of late effects in survivors of pediatric cancer. A prospective study, assessing a large population of patients, is needed to determine the underlying causes and to develop primary and secondary prevention strategies.


Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy.
Hemorrhage related to cerebral amyloid angiopathy (CAA) appears to occur through a multistep pathway that includes deposition of beta-amyloid in cerebral vessels and specific vasculopathic changes in the amyloid-laden vessels, such as cracking of the vessel wall. Recent reports suggest a positive association between CAA-related hemorrhage and both the apolipoprotein E (APOE) epsilon4 allele and, unexpectedly, the APOE epsilon2 allele. Unlike APOE epsilon4, APOE epsilon2 does not appear to act through increased beta-amyloid deposition. We therefore sought to determine whether it might specifically accelerate the second step in this pathway, that is, development of the vasculopathic changes that lead to hemorrhage. To determine the role of APOE in development of vasculopathic changes, we compared APOE genotypes in two groups of postmortem brains: 52 brains with complete amyloid replacement of vessel walls but without vasculopathic changes, and 23 brains with complete amyloid replacement of vessels with the accompanying changes of cracking of the vessel wall and paravascular leaking of blood. Frequency of APOE epsilon2 was significantly greater in the group with vasculopathy (0.09) than the group without (0.01, p = 0.03). The groups did not differ in mean age or extent of neuritic plaques. Analysis of a clinical series of patients with CAA-related hemorrhage confirmed an overrepresentation of APOE epsilon2 as well as an association between this allele and earlier age of first hemorrhage. These data suggest that APOE epsilon2 and epsilon4 might promote CAA-related hemorrhage through separate mechanisms: epsilon4 by enhancing amyloid deposition and epsilon2 by causing amyloid-laden vessels to undergo the vasculopathic changes that lead to rupture.


Gallic Acid Potentiates the Antimicrobial Activity of Tulathromycin Against Two Key Bovine Respiratory Disease (BRD) Causing-Pathogens.
Bovine respiratory disease (BRD) is the most common infectious disease in dairy and beef cattle. It is associated with significant morbidity and mortality and causes a huge economic loss each year. In western Canada, a one-time injection of tulathromycin is commonly used as a metaphylactic procedure to reduce BRD incidence and eliminate potential BRD outbreak. With increased global concern on antimicrobial usage in dairy and beef products and bacterial resistance to antimicrobials, it is important to develop a novel strategy to eliminate the usage or decrease the dosage of antimicrobials. In this study, we showed that gallic acid was active against both Mannheimia haemolytica and Pasteurella multocida, two key BRD associated-pathogens, with the minimum inhibitory concentration (MIC) measured at 250 and 500 μg/mL, respectively. Co-administration of tulathromycin and gallic acid exhibited a strong additive or weak synergistic effect toward both M. haemolytic and P. multocida. Tulathromycin, gallic acid and their combination were also effective against the mixed culture of M. haemolytic and P. multocida. Furthermore, we showed that pre-exposure to tulathromycin generated bacterial resistance to the antimicrobial in M. haemolytica but not in P. multocida.


3D Auxetic Metamaterials with Elastically-Stable Continuous Phase Transition.
In solid state physics, phase transitions can influence material functionality and alter their properties. In mechanical metamaterials, structural-phase transitions can be achieved through instability or buckling of certain structural elements. However, these fast transitions in one mechanical parameter typically affect significantly the remaining parameters, hence, limiting their applications. Here, this limitation is addressed by designing a novel 3D mechanical metamaterial that is capable of undergoing a phase transition from positive to negative Poisson's ratio under compression, without significant degradation of Young's modulus (i.e. the phase transition is elastically-stable). The metamaterial is fabricated by two-photon lithography at the micro-scale and its mechanical behavior is assessed experimentally. For another choice of structural parameters, it is then shown that the auxetic behavior of the considered 3D metamaterial class can be maintained over a wide range of applied compressive strain.


Presenile dementia syndromes: an update on taxonomy and diagnosis.
The four major degenerative dementias that often begin in presenescence: are reviewed. These are Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and Creutzfeldt-Jakob disease. Their epidemiological, genetic, and clinical features are reviewed, and controversies in taxonomy arising from recent discoveries described. Particular attention is given to the pathological role of protein aggregation, which appears to be a factor in each disease.


Field survey of Glycyrrhiza plants in central Asia (2). Characterization of phenolics and their variation in the leaves of Glycyrrhiza plants collected in Kazakhstan.
A new prenylated flavanone, licoleafol, and a new prenylated dihydrostilbene, uralstilbene, together with four known compounds, 8-dimethylallyleriodictyol, sophoraflavanone B, gancaonin R, and 6-dimethylallyleriodictyol, were isolated from the leaves of Glycyrrhiza uralensis collected in Kazakhstan. HPLC analysis of the leaves of Glycyrrhiza plants collected in Kazakhstan showed that both G. uralensis-specific and Glycyrrhiza glabra-specific compounds were detected in the leaves of the morphologically intermediate-type plants, suggesting that the intermediate-type plant is a hybrid of G. glabra and G. uralensis. In addition, HPLC profiles of leaf extracts from offspring of intermediate-type plants were divided into the three types: the G. uralensis type, G. glabra type, and the intermediate type. From these results, it appears likely that the intermediate-type plant back-crosses with G. glabra and G. uralensis to generate a G. glabra-type plant and a G. uralensis-type plant, respectively.


A Switchable One-Compound Diode.
A diode requires the combination of p- and n-type semiconductors or at least the defined formation of such areas within a given compound. This is a prerequisite for any IT application, energy conversion technology, and electronic semiconductor devices. Since the discovery of the pnp-switchable compound Ag10 Te4 Br3 in 2009, it is in principle possible to fabricate a diode from a single material without adjusting the semiconduction type by a defined doping level. Often a structural phase transition accompanied by a dynamic change of charge carriers or a charge density wave within certain substructures are responsible for this effect. Unfortunately, the high pnp-switching temperature between 364 and 580 K hinders the application of this phenomenon in convenient devices. This effect is far removed from a suitable operation temperature at ambient conditions. Ag18 Cu3 Te11 Cl3 is a room temperature pnp-switching material and the first single-material position-independent diode. It shows the highest ever reported Seebeck coefficient drop that takes place within a few Kelvin. Combined with its low thermal conductivity, it offers great application potential within an accessible and applicable temperature window. Ag18 Cu3 Te11 Cl3 and pnp-switching materials have the potential for applications and processes where diodes, transistors, or any defined charge separation with junction formation are utilized.


Assessing the prevalence of hepatitis B virus infection among health care workers in a referral hospital in Kisantu, Congo DR: a pilot study.
We aimed to determine hepatitis B virus (HBV) prevalence and risk factors for health care workers (HCWs) to contract HBV infection in a referral hospital in the Democratic Republic of Congo. From October 2015 to August 2016, we recruited 97 HCWs (55 males and 42 females, aged 41.2 ± 10 yr) from Kisantu St. Luke's Hospital, a Congolese referral hospital located in the province of Kongo Central. Serum samples were assayed for HBV markers using ELISA. A questionnaire was used to record the HCWs' demographics, medical histories, and risk factors. The overall prevalence of exposure to HBV infection [HBsAg+, and/or hepatitis B core antibody (anti-HBc)+] was 56.7% (55/97). HBsAg positivity was found in 18.6% (18/97) of the HCWs whereas 29.9% (29/97) were anti-HBc positive. Approximately 8.2% (8/97) of the HCWs tested positive for both HBsAg and anti-HBc. Being a physician [odds ratio (OR)=2.8 (95% CI: 1.34-12.23)], a laboratory technician [OR=3.35 (95% CI: 1.35-5.21)], and having multiple sex partners [OR=3.05 (95% CI: 1.13-9.09)] were found to be factors associated with HBV infection. Exposure to HBV is common among HCWs at Kisantu St. Luke's Hospital. Isolated HBsAg was also prevalent among them. There is a high risk that HBV could be spread to others. Therefore, there is an urgent need for HBV screening, treatment, and vaccination policies.


Herpecaudin from Herpetospermum caudigerum, a Xanthine Oxidase Inhibitor with a Novel Isoprenoid Scaffold.
Herpecaudin (3), a xanthine oxidase inhibitor with an unprecedented scaffold, was discovered from Herpetospermum caudigerum seeds. The structure was determined by spectroscopic and X-ray single crystallographic methods. A possible biogenetic pathway leading to herpecaudin is proposed, starting from congeners 23,24-dihydrocucurbitacin E (1) and endecaphyllacin B (2), and involving retro-aldol cleavage as a key step. All three compounds proved to be active and represent new scaffolds of non-purine analogue xanthine oxidase inhibitors.


Bioinspired Platform Conjugated Active Drug Delivery.
The rapid emergence of nanotechnology and biotechnology has enabled revolutionary developments for drug delivery systems. Recently, drug delivery has attracted extensive research interest; applied to improve the functions of these carriers and their applications. Active drug delivery is currently approved as an ideal approach for targeted transport in a biological entity and can cooperate with therapeutic mediums in transporting cargoes. In this review, several active targeted cargomediated drug delivery patterns have been summarized, including molecular motors, bio-camouflaged particles, and self-propelled nanomotors. Subsequently, a series of active targeted carriers for drug delivery were introduced, and their ability for targeted binding was discussed. Furthermore, the mechanism of active targeted transport was exposited in detail, and some promising works are highlighted.


Do Restrictions on Antipsychotic Use Differ Between Medicare Part D Stand-Alone Versus Medicare Advantage Plans?
The objective of this study was to describe the type of restrictions and differences among antipsychotic users enrolled in Medicare Part D Stand-Alone (PDPs) and Advantage (MAPDs) prescription drug plans. This retrospective study used data from Chronic Condition Data Warehouse, comprising a random 5% sample of the Medicare population in 2008. This study used bivariate analyses and multivariate logistical regression models to study differences in formulary restrictions on antipsychotic use between PDP and MAPD enrollees, adjusting for enrollee characteristics. Dependent variables included type of restriction and antipsychotic therapeutic class. The study sample was restricted to continuous Part D enrollees (N = 1,346,978) stratified by plan type, MAPDs (N = 435,591), and PDPs (N = 911,387). According to the bivariate analysis, antipsychotic users enrolled in PDPs were more likely to encounter restrictions (39.8%), compared with those in MAPDs (30.3%). In the multivariate analyses, antipsychotic users in MAPDs were less likely to face any restriction (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.72-0.78). Furthermore, atypical antipsychotic users in MAPDs were less likely to face any restriction (OR = 0.76, 95% CI 0.73-0.79), while first-generation antipsychotic users in MAPDs were more likely to face any restriction (OR = 1.87, 95% CI 1.32-2.65). Low-income subsidy (LIS) beneficiaries using any antipsychotic were much more likely to face restrictions compared with non-LIS beneficiaries. PDP enrollees prescribed antipsychotics were more likely to face formulary restrictions, as opposed to those in MAPDs. LIS beneficiaries enrolled in PDPs faced much higher risk of restricted access to this "protected" drug class.


Original article Muscle extracellular matrix degradation and contractibility following tendon rupture and disuse.
Muscle extracellular matrix (ECM) plays an important role in maintaining muscular integrity and force transduction. However, the role of ECM in skeletal muscle atrophy remains unknown. In this study, we employed two clinically relevant mouse models of Achillotenotomy and hindlimb suspension to simulate Achilles tendon rupture and hindlimb disuse. The gastrocnemius was harvested following two weeks of treatment. We hypothesized that degradation of muscle ECM basement membrane lead to dysfunction of muscle contractility. Our results demonstrated a significant reduction of gastrocnemius single twitch force, isometric tetanic force, and contraction velocity following tendon rupture (p<0.001), but not disuse. Additionally, up-regulation of matrix metalloproteinase-2 (MMP-2) was observed only after tendon rupture (p=0.00234). These findings suggest that ECM remodeling and basement membrane degradation due to MMP-2 may be responsible for declined muscle contractibility. Inhibiting ECM degradation enzymes may be a potential treatment strategy for skeletal muscle atrophy after tendon rupture.


Endonucleolytic activities of nuclei from rat ascites hepatoma.
By autodigestion (endogenous endonucleolysis) of rat liver (RL) or rat-ascites hepatoma (AH) nuclei, the nucleosomes were released from the RL, but not from the AH, nuclei. In contrast, by micrococcal nuclease digestion (exogenous endonucleolysis), the nucleosomes were released more rapidly from the AH than from the RL nuclei. A 0.6 M NaCl extract of the RL or AH nuclei was filtered through a Sephadex G-100 column. The resulting topoisomerase fraction was subjected to DNA relaxation and catenation assays with pBR322 DNA as a substrate. Consequently, the relaxation activity was almost the same between the RL and AH fractions, whereas the catenation activity was much higher in the AH fraction.


Scientific evaluation of clinical interventions in resuscitation medicine.
The image of the physician as a therapist, as well as the general perception of the physician's role in society and in the life of patients and their families, has changed dramatically in past decades. In response, many conferences, editorials, and planning activities for medical and premedical curricula have been devoted to the subject of restoring the elements of compassion and personal involvement to the relationship between physician and patient. Nonetheless, the change in the doctor-patient relationship might merely reflect the growing indifference to people as individuals that seems to pervade our society in all service-related areas. Although the loss is particularly objectionable for the sick, some may claim it is compensated by scientifically superior care in present-day medical practice. This paper will reflect briefly on past and present views of medical care and its evaluation. It will conclude that a scientifically sound evaluation of treatment might also offer a solution for restoration of human elements in the delivery of medical care.


Reduction of plasma fibrinolytic activity following high-dose cyclophosphamide is neutralized in vivo by GM-CSF administration.
GM-CSF has broad clinical applicability as a potent myelopoietic stimulator. However, its function is not restricted to the myelopoietic system and several observations suggest that GM-CSF may interfere with the hemostatic balance. In order to assess whether GM-CSF has any influence on hemostasis, we evaluated some coagulative and fibrinolytic parameters in patients treated with GM-CSF following chemotherapy. Fibrinolytic activity (FA), fibrinogen and D-dimer were evaluated before and after high-dose cyclophosphamide in 6 patients additionally treated with GM-CSF and in 5 control patients; moreover, tissue plasminogen activator (tPA) was assayed in those treated with GM-CSF. Comparative in vitro analysis was performed on cultured endothelial cells before and after exposure to GM-CSF. Control patients showed a significant decrease in plasma FA after chemotherapy compared to basal values (FA/mm2: 15.6 +/- 2.1 at day + 2 and 20.8 +/- 19 at day + 4 vs. 103.8 +/- 64.2 at day 0; p < 0.005); conversely, no FA reduction was observed in GM-CSF-treated subjects. In this latter group a marked increase in tPA antigen was seen, consistent with enhanced FA. No significant changes in plasma D-dimer and fibrinogen values were detected in the two groups. tPA, urokinase-type plasminogen activator, PAI-1 and procoagulant activity were evaluated in vitro on cultured human endothelial cells and found to be unchanged following GM-CSF addition. The results demonstrate that high-dose chemotherapy may negatively influence plasma FA. This adverse side effect is neutralized by GM-CSF administration. The discrepancy found between in vitro and in vivo GM-CSF activity on hemostatic may be explained by in vivo GM-CSF stimulation of cell types other than endothelial cells.


Potential of Equisetum ramosissimum Desf. for remediation of antimony flotation tailings: a case study.
A flooding event caused collapsing of the Stolice flotation tailing dam and spilling of large volumes of sludge into environment. Urgent remediation measures have not been applied due to the lack of financial resources. Remediation values for Sb, Zn, and Pb in the flotation tailing samples were exceeded 20.5, 4.2, and 1.15 times, respectively, emphasizing the need for remediation. Plants growing on mine spoils represent useful tools for environmental monitoring and soil remediation. The appearance of Equisetum ramosissimum as a dominant colonizer on the flotation tailings indicates that biological reclamation of the site is possible. Equisetum ramosissimum shows the ability to phytostabilize and immobilize available fractions of Fe, Mn, Zn, Pb, and Sb. Transfer rate of metals from roots to shoots reveals exclusion of elements from the shoots, preventing their further spreading through the food chain. The results of this study show that E. ramosissimum can be an additional tool for environmental monitoring and remediation of flotation tailings after hazardous events.


Neonatal necrotizing enterocolitis associated with penicillin-resistant, toxigenic Clostridium butyricum.
The cause of neonatal necrotizing enterocolitis (NEC) is unknown. An association between NEC and clostridial infection has been reported from several centers, but the organisms have not been extensively characterized. Clostridium butyricum was isolated from the peritoneal fluid and cerebrospinal fluid of a neonate with NEC. The organism was resistant to the penicillins, but sensitive to vancomycin. Toxin production was demonstrated. Although the role of clostridial toxins in the pathogenesis of NEC is unknown, clostridial toxins are well established as the causes of two other intestinal diseases (antibiotic-associated pseudomembranous colitis and pig-bel). Further investigation of the role of clostridia in the pathogenesis of NEC and of the use of oral, nonabsorbable antibiotics in the treatment of NEC is needed.


Regional Anesthesia for Acute Pain Treatment in Pre-Hospital and In-Hospital Emergency Medicine: Pain of Musculoskeletal Origin.
More than half of all emergency department patients seek help for acute pain, which is usually of musculoskeletal origin. Acute pain is often inadequately treated even today, particularly in children and in older patients. In this study, we assess the potential role of regional anesthetic methods in improving the treatment of pain in the preclinical and clinical emergency setting. Pain-related reasons for admission were identified and quantified from emergency admission data. A structured literature search was carried out for clinical studies on the treatment of pain in the emergency setting, and a before-and-after comparison of the pain relief achieved with established vs. newer regional anesthetic methods was performed. 43% of emergency patients presented with acute musculoskeletal pain. The literature search yielded 3732 hits for screening; data on entity-specific pain therapy spectra were extracted from 153 studies and presented for the main pain regions. The degree of pain relief obtained through regional anesthetic procedures, on a nominal rating scale from 0 to 10, was 4 to 7 points for acute back and chest wall pain, >6 for shoulder pain, 5 to 7 for hand and forearm injuries, and >4 for hip fractures. These results were as good as, or better than, those obtained by analgesia/sedation with strong opioids. Modern regional anesthetic techniques can improve acute pain management in the emergency department and, to some extent, in the pre-hospital setting as well. Pain relief with these techniques is quantifiably better than with strong opioids in some clinical situations; moreover, there is evidence of further advantages including process optimization and fewer complications. Data for comparative study remain scarce because of a lack of standardization.