[Role of Ca-125 in the differential diagnosis of adnexal mass in breast cancer patients].
Serum CA-125 is of value in differential diagnosis of benign and malignant adnexal masses, especially in postmenopausal women. In ovarian cancer preoperative CA-125 levels are related to tumor stage, histologic grade, but are not an independent prognostic factor. The aim of our study was to determine CA-125 serum level in women with ovarian tumor treated previously because of breast cancer. Due to our research, we examined 51 women operated on for adnexal masses in the Department of Oncological Gynaecology in Bydgoszcz, 1996 - 2002. All those patients were treated because of breast cancer previously. In 19 women (37,3%) benign ovarian tumors were found, in 4 cases (7,8) - primary ovarian cancer whereas in 28 patients (54,9%) breast cancer metastases were detected. Based on CA-125 levels before surgery, correlation between CA-125 concentration and malignant histologic type was observed. 1. Higher CA-125 serum levels were found in a group of patients with metastatic adnexal masses compared to primary ovarian cancer. 2. In a group of women with breast cancer and ovarian tumor, metastatic adnexal masses were observed in more than 50% of cases.


Epithelioid sarcoma of penis.
A rare case of an epithelioid sarcoma of the penis arising as a superficial plaque in the glans and causing pain on erection is reported. This tumor is characterized by a slow growth and infiltrative pattern with a high propensity for local recurrence. Proper treatment is wide local excision.


Graphene oxide quantum dot-sensitized porous titanium dioxide microsphere: Visible-light-driven photocatalyst based on energy band engineering.
We report a novel graphene oxide quantum dot (GOQD)-sensitized porous TiO2 microsphere for efficient photoelectric conversion. Electro-chemical analysis along with the Mott-Schottky equation reveals conductivity type and energy band structure of the two semiconductors. Based on their energy band structures, visible light-induced electrons can transfer from the p-type GOQD to the n-type TiO2. Enhanced photocurrent and photocatalytic activity in visible light further confirm the enhanced separation of electrons and holes in the nanocomposite.


In vitro anticancer activity of a pentacyclic triterpenoid via the mitochondrial pathway in bone-invasive oral squamous cell carcinoma.
Oral cancer is the most dreadful cancer worldwide with a 5-year survival rate of approximately 50%. Anticancer therapies such as chemotherapy and radiotherapy result in severe side effects. We aimed to evaluate the in vitro anticancer activity of Asiatic acid (AA) on bone-invasive oral squamous cell carcinoma (BHY) cell line. This was an in vitro laboratory setting. BHY cell lines were used for the experiment. Confocal microscopy was used to observe cellular alterations. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the IC50 concentration of AA and flow cytometry to analyze the percentage of cells in each phase of the cell cycle post treatment. Immunoblot assays and semiquantitative reverse transcriptase-polymerase chain reaction (rt-PCR) were used to study the expression level of genes involved. Student's t-test and one-way analysis of variance were used for statistical analysis. IC50 concentration of AA was 15.6 μM. On flow cytometry analysis, treatment with 15.6 μM and 31.25 μM of AA for 24 h increased the percentage of cells in the G2/M phase to 45.63% and 53.12%, respectively, compared to 9.62% in control group. Immunoblot analysis and semiquantitative rt-PCR demonstrated an upregulation of p53, cyclin-dependent kinase inhibitors (p21 and p27), caspase-3, caspase-9, cytochrome c and Bax in a time-dependent manner and downregulation of cyclins and anti-apoptotic protein Bcl-2 (**P < 0.05, ***P < 0.001 versus control) post AA treatment. AA induces apoptosis via the mitochondrial-dependent pathway and causes cell cycle arrest at the G2/M phase in BHY cell line.


Relationship between natural variations in motoneuron number and body size in Xenopus laevis: a test for size matching.
During normal development, tadpoles of Xenopus laevis demonstrate large variations in body size that are carried through metamorphosis. This variation in size exists at the stages when lumbar lateral motor column (L-LMC) motoneurons are produced and when neuronal cell death in this neuron population occurs. Body size, hindlimb size, motoneuron number, and motoneuron size (i.e., neuron nuclear cross-sectional area) were measured in animals from three developmental stages: one prior to significant amounts of cell death, one at the peak rate of cell death, and one after cell death. The hypothesis that neuron population size is matched to peripheral size was tested by using the natural size variation found at each of these stages. The ranges of values for the measurements at the three stages were large. Significant correlations between body size and motoneuron number, as well as between motoneuron number and muscle fiber number, were present after cell death. Since these correlations emerged as cell death reduced neuron numbers, size matching may have occurred and cell death may have adjusted the L-LMC motoneuron population's size to variation in body size. In addition to the correlations between body size and motoneuron number at the end of cell death, neuron numbers before and after cell death were significantly correlated among groups of siblings. The possibility that the number of neurons after cell death was also influenced by differences in the number of L-LMC progenitors is discussed.


Time-dependent effects of reserpine on retention of passive avoidance.
Reserpine produced amnesia for a one-trial passive avoidance task when given 2, 3, 4, 5 hr before but not when given 1, 8, 12, 24 hr or 30 min before, immediately, 90 min or 2, 4, 5, 6, 8, 9, 12, 24 hr following training. The results were discussed in terms of the reserpine effect on biogenic amines and their possible role in memory formation.


Multimodal approach and long-term survival in a patient with recurrent metastatic acinar cell carcinoma of the pancreas: A case report.
Pancreatic acinar cell carcinoma is an uncommon neoplasm of the exocrine pancreas associated with a poor prognosis, especially when found to be metastatic. Since there are a lack of large studies and prospective, randomized data, no consensus treatment guidelines are available. Here, we report a case of a patient with recurrent metastatic acinar cell carcinoma involving the liver who had presented initially with pancreatic panniculitis. She received chemotherapy with capecitabine and oxaliplatin prior to resection of her primary tumor and liver metastases, after which she experienced a 30 months recurrence-free survival. Upon relapse, she was treated with a combination of capecitabine and oxaliplatin followed by maintenance capecitabine. Now, more than seven years after initial diagnosis, the patient remains stable without evidence of active disease. This case highlights the possibility of therapeutic success even for a patient initially deemed unresectable due to a poor performance status who responded to fluoropyrimidine-based therapy.


[Experimental acceleration of fracture repair by biochemical media (author's transl)].
The influence of calcitonine, amino acids, ribonucleid acids, kallikrein, growth hormone, and cyclic adenosine 3'5' monophosphate on fracture repair was tested in rabbits. To obtain an objective measurement of callus stability the bones were bent mechanically. The force applied and the degree of bending were recorded continuously. The slope of the curve was taken as a parameter of callus stability. In the series with calcitonine no influence on fracture healing was found. Injections of ribonucleic acids, amino acids, kallidrein, and growth hormone demonstrated a limited effect on bone repair. Callus formation was stimulated by adenosine 3'5' monophosphate. Optimal results were achieved by a combination of adenosine 3'5' monophosphate, amino acids, ribonucleic acids, and kallikrein.


Prediction of the prognosis of somatoform disorders using the Minnesota Multiphasic Personality Inventory.
Somatoform disorders are frequently resistant to treatment. This study aimed to determine the utility of the Minnesota Multifaceted Personality Inventory (MMPI) in predicting the prognosis of somatoform disorders. Overall, 125 patients diagnosed with somatoform disorders between January 1, 2013 and December 31, 2017 in the psychiatric department of Fukushima Medical University Hospital were included. Patients with positive outcomes were identified based on a subjective estimation regarding (1) pain and (2) social functions, including activities of daily living. They were divided into the improved group (IG) and the non-improved group (NIG). Each factor was then descriptively compared between the two groups, and the sensitivity and specificity were determined. The NIG had significantly higher scores but only on the Hy scale. Thus, the optimal Hy scale cutoff score was calculated. The cutoff point was 73.5, with a sensitivity of 55.7% and a specificity of 71.7%. An MMPI Hy scale score higher than a cutoff value of 73.5 predicts a poor response to conventional supportive psychotherapy or drug therapy in patients with somatoform disorders. This cutoff point may be used as an important index for selecting treatment for somatoform disorders.


Design of an artificial restriction enzyme having simultaneous DNA cleavage activity.
We designed dimeric distamycin linked hydroxamic acid (DDHA)-metal complexes and investigated double strand simultaneous cleavage. Compared as distamycin linked hydroxamic acid (DHA)-metal complex, DDHA-metal complex cleaved DNA at the same level of DHA-metal complex without double strand simultaneous cleavage.


An ex vivo multiparametric flow cytometry assay using human whole blood to simultaneously measure cytotoxicity and leishmanicidal activities.
Therapeutic options for the treatment of leishmaniasis are insufficient and need improvements owing to their low efficiency and high toxicity as well as the emergence of resistant strains. The limited number of new drugs for neglected diseases and lack of innovation in your development are still challenges. In this context, the process of discovery and development of biological assays play a pivotal role for the identification of bioactive compounds. The assays currently used for screening of drugs with cytotoxic activity against Leishmania parasites, include different processes that utilize intact parasite (free or intracellular) or specific enzymes of metabolism as a target cell. These assays allow the screening of large numbers of samples followed by more detailed secondary confirmatory assays to confirm the observed activity and assess their toxicity. In the present study, we described the development of a new functional and more complete assay that enables simultaneous assessment of potential anti-Leishmania compounds through evaluation of internalization of fluorescein-labeled L. braziliensis promastigotes by human peripheral blood monocytes and their cytotoxicity by flow cytometry. We standardized the conditions for parasite labeling to achieve better phagocytosis analysis by setting the ratio of number of parasites per cell as 1 to 2, at incubation time of 6h. The cytotoxicity assessment was performed by the quantification of cells undergoing early/late apoptosis and necrosis using a double labelling platform employing 7AAD for late apoptosis and necrosis analysis and Annexin-V for early apoptosis evaluation. Hemolysis analysis was an additional parameter to test cytotoxicity. Two drugs used on clinic (Amphotericin B and Glucantime®) were used to validate the proposed methodology, and the assay was able to detect their known leishmanicidal activity and immunotoxicity properties. This new predictive assay will contribute to the development of translational medicine strategies in drug discovery for neglected diseases such as leishmaniasis.


Facilitating the process of critical thinking for nursing.
An exploratory study was conducted during 1995 to examine the degree to which critical thinking was encouraged in nursing education throughout New South Wales (NSW), Australia. The study identified whether a sample of graduate nurses and nurse educators at 12 faculties of nursing in NSW shared similar ideas about what critical thinking entails, the best ways in which to develop critical thinking processes and whether critical thinking is a reasonable way for nurses to achieve skilled and effective nursing interventions. The findings indicate that both nursing students and nurse educators favour the facilitation of critical thinking for nursing for very practical reasons. These refer to improving professional standards of practice, stimulating inquiry and promoting sound reasoning in practice, as well as contributing to personal and professional development. Study participants were found to favour a variety of teaching and learning strategies for critical thinking, and this finding is the focus for this discussion paper. The majority of participants stated that nurses would perhaps be better able to abstract principles of thinking from the specific contexts in which they are practised. Strategies found effective for nursing practice included a variety of approaches: direct learning of skills that contribute to critical thinking, such as analysis; infusion, or integration of critical thinking in all areas of learning; and learning to think critically within distinct disciplines of thought. Analysis of the findings, therefore, suggests that critical thinking is thought to be an important component of nursing practice and that in nursing it is a complex activity, requiring a combination of dispositions, abilities and approaches that can be developed by drawing on a range of learning strategies.


[Lipoma of the stomach. Presentation of a case and a review of cases reported in Spain].
Gastric lipoma is an infrequent benign submucosal tumor that is usually asymptomatic. In view of the few reports of this pathology in the Spanish and international bibliography, a new case that debuted as massive upper gastrointestinal hemorrhage is communicated. We reviewed the cases published in Spain to date, emphasizing the methodology of preoperative diagnosis, with special attention to the endoscopic signs characterizing gastric lipoma and computerized axial tomography, which is now viewed as the technique of choice. Therapeutic options are discussed.


Knowledge, attitudes, and practices of university students regarding COVID-19: a cross-sectional study in Vietnam.
This cross-sectional study investigated the knowledge, attitudes, and practices (KAP) of Vietnamese university students regarding COVID-19. A validated questionnaire (Cronbach's alpha = 0.71) was used to survey 1,025 students. A convenience sampling method was used for recruiting students from April to May 2022. The Wilcoxon rank-sum test and the Kruskal-Wallis rank-sum test/Dunn test for multiple comparisons were employed to compare students' KAP scores between two groups and among three groups or more, respectively. Factors associated with students' COVID-19 KAP scores were determined via univariate and multivariate linear regression models. Variables in the multivariate linear regression models were chosen using the Bayesian Model Averaging method in R software version 4.2.0. A majority of students had good knowledge (75.61%), positive attitudes (98.24%), and good practices toward COVID-19 (94.93%). Regarding the COVID-19 knowledge, the proportions of students who knew that mosquito bites and exposure to/eating wild animals would not lead to COVID-19 infection were not high (47.22 and 34.34%, respectively). More importantly, 70.34% of students thought that vitamins and minerals could help prevent or cure COVID-19. Antibiotics were the first choice for COVID-19 treatment of 438 students (42.73%). Nearly half of students (48.0%) bought antibiotics to keep at home in case of COVID-19 infection. The average KAP scores of medical students (19.97 ± 3.99, 45.10 ± 3.94, 9.72 ± 1.78) and females (18.67 ± 4.44, 44.79 ± 3.79, 9.36 ± 1.84) were significantly higher than those of non-medical students (16.48 ± 4.37, 43.33 ± 4.03, 8.68 ± 1.87) and males (17.01 ± 4.55, 42.79 ± 4.39, 8.77 ± 1.97), respectively (p < 0.001). Older students were more likely to have good knowledge and practices than the younger ones (p < 0.001). In addition, students using websites of the World Health Organization/the Ministry of Health and scientific articles to seek COVID-19 information were significantly associated with higher KAP scores when compared with those not using these sources (p < 0.001, p < 0.001, and p = 0.00139, respectively). Students' KAP scores significantly varied by age, sex, major, and sources of COVID-19 information. Although many students had sufficient knowledge, positive attitudes, and good preventive practices toward COVID-19, additional education and training strategies are paramount, especially for non-medical students and males.


A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.
We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. Dendritic cells (DCs) play an activation role in acute rejection (AR). Thus, the present study was designed to investigate the effects of CHBP on DCs in a rat renal transplantation model. The left kidney was harvested from male Lewis rats and then transplanted into male Wistar rats with or without CHBP treatment. Five successive treatment doses of CHBP after transplantation significantly ameliorated AR with lower histological injury, apoptosis and CD4(+) and CD8(+) T-cell infiltration in renal allografts. CHBP reduced IFN-γ and IL-1β levels but increased IL-4 and IL-10 levels in the serum. The number of mature DCs was significantly decreased in renal allografts treated with CHBP. In addition, incubating DCs with CHBP in vitro led to reduction in TNF-α, IFN-γ, IL-1β and IL-12 levels and increase of IL-10 expression at the protein level in the supernatant. Mechanistically, CHBP inhibited TLR activation-induced DC maturation by increasing SOCS1 expression through Jak-2/STAT3 signaling. In conclusion, CHBP suppresses renal allograft AR by inhibiting the maturation of DCs via Jak-2/STAT3/SOCS1 signaling, suggesting that CHBP may be an potential therapeutic drug for treating renal AR.


Author Correction: Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations.
Change history In this Letter, there are several errors regarding the assignments of mtDNA haplotypes for a subset of egg donors from our study. These errors have not been corrected online.


Spectrophotometric determination of cyclotrimethylenetrinitramine (RDX) in explosive mixtures and residues with the Berthelot reaction.
On-site colorimetric methods are a valuable, cost-effective tool to assess the nature and extent of contamination in remediated sites and to enable on-site screening for police criminology laboratories. The existing colorimetric method for cyclotrimethylenetrinitramine (RDX) based on a Griess reaction suffers from the non-quantitative reduction to nitrite and from the unstable character of HNO2 in acidic medium. Thus we propose a novel spectrophotometric RDX assay in explosive mixtures and residues, based on (Zn+HCl) reduction of RDX in a microwave oven, followed by neutralization of the reduction products to ammonia and low molecular-weight amines, and Berthelot reaction of these amine-compounds with phenol and hypochlorite in alkaline medium to give an intensely blue indophenol dye absorbing at 631nm. The molar absorptivity and limit of detection (LOD) for RDX were (1.08+/-0.04)x10(4) L mol(-1) cm(-1) and 0.18 mg L(-1), respectively. Application of the method to synthetic mixture solutions of RDX and trinitrotoluene (TNT) at varying proportions showed that there was minimal interference from TNT (which could be compensated for by dicyclohexylamine colorimetry), since the Berthelot reaction was essentially non-responsive to m-substituted anilines derived from TNT upon (Zn+HCl) reduction. The proposed method was successfully applied to military-purpose explosive mixtures of (RDX+inert matter) such as Comp A5, Comp C4, and Hexal P30, and to (RDX+TNT) mixtures such as Comp B. The molar absorptivity of RDX was much higher than that of either ammonium or nitrate; RDX could be effectively separated from ammonium and nitrate in soil mixtures, based on solubility differences. The Berthelot method for RDX was statistically validated using Comp B mixtures against standard HPLC equipped with a Hypersil C-18 column with (40% MeOH-60% H2O) mobile phase, and against gas chromatography-thermal energy analysis (GC-TEA) system.


Nifedipine prevents iron accumulation and reverses iron-overload-induced dopamine neuron degeneration in the substantia nigra of rats.
The mechanisms of iron accumulation in substantia nigra (SN) of Parkinson's diseases remain unclear. The objective of this study was to investigate effects of nifedipine on iron-overload-induced iron accumulation and neurodegeneration in SN of rats. By high performance liquid chromatography-electrochemical detection, tyrosine hydroxylase (TH) immunohistochemistry, and iron content array, we first quantified iron content and the number of dopamine neurons in SN of experimental rats treated with iron dextran. We further assessed effects of treatment with nifedipine. Our results showed that nifedipine treatment prevents iron dextran-induced dopamine depletion in the striatum. Consistently, we found that nifedipine restores the number of TH-positive neurons reduced by iron dextran overload and prevents increase of iron content in the SN. These results suggested that nifedipine may suppress iron toxicity in dopamine neurons and prevent neurodegeneration.


Biofilm plasmids with a rhamnose operon are widely distributed determinants of the 'swim-or-stick' lifestyle in roseobacters.
Alphaproteobacteria of the metabolically versatile Roseobacter group (Rhodobacteraceae) are abundant in marine ecosystems and represent dominant primary colonizers of submerged surfaces. Motility and attachment are the prerequisite for the characteristic 'swim-or-stick' lifestyle of many representatives such as Phaeobacter inhibens DSM 17395. It has recently been shown that plasmid curing of its 65-kb RepA-I-type replicon with >20 genes for exopolysaccharide biosynthesis including a rhamnose operon results in nearly complete loss of motility and biofilm formation. The current study is based on the assumption that homologous biofilm plasmids are widely distributed. We analyzed 33 roseobacters that represent the phylogenetic diversity of this lineage and documented attachment as well as swimming motility for 60% of the strains. All strong biofilm formers were also motile, which is in agreement with the proposed mechanism of surface attachment. We established transposon mutants for the four genes of the rhamnose operon from P. inhibens and proved its crucial role in biofilm formation. In the Roseobacter group, two-thirds of the predicted biofilm plasmids represent the RepA-I type and their physiological role was experimentally validated via plasmid curing for four additional strains. Horizontal transfer of these replicons was documented by a comparison of the RepA-I phylogeny with the species tree. A gene content analysis of 35 RepA-I plasmids revealed a core set of genes, including the rhamnose operon and a specific ABC transporter for polysaccharide export. Taken together, our data show that RepA-I-type biofilm plasmids are essential for the sessile mode of life in the majority of cultivated roseobacters.


Comparison and evaluation of analysis procedures for the quantification of (2-methoxyethoxy)acetic acid in urine.
Several extraction and derivatization procedures were evaluated for the quantification of (2-methoxyethoxy)acetic acid (MEAA) in urine. MEAA is a metabolite and a biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether with widespread use in various industrial applications and the specific use as an anti-icing additive in the military jet fuel formulation JP-8. Quantification of glycol ether biomarkers is an active area of analytical research. Various sample preparation procedures were evaluated: liquid-liquid extraction (LLE) using ethyl acetate yielded the highest recovery, and solid-phase extraction (SPE) gave low recovery of MEAA. Two derivatization procedures were thoroughly investigated and validated, namely, silylation of MEAA with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), and esterification of MEAA using ethanol. Quantification was performed by gas chromatography (GC) with a mass spectrometer as detector and using a polydimethylsiloxane (HP-1) capillary column. Deuterated 2-butoxyacetic acid (d-BAA) was used as an internal standard. Recovery studies of spiked human urine demonstrated the accuracy and precision of both procedures. The limit of detection (LOD) and other figures of merit for both derivatization procedures will be discussed in detail. Applications of these analysis procedures are also discussed.


Semantic facilitation and translation priming effects in Chinese-English bilinguals.
In two experiments, semantic facilitation and translation priming effects in Chinese-English bilingual speakers were demonstrated with a lexical decision task. A 300-msec stimulus-onset asynchrony (SOA) was used between display of the prime and the target item. Experiment 1 showed that subjects' lexical decision responses were facilitated to a greater extent when primed by a translation equivalent than a semantically related between-language word. In Experiment 2, we found that pictorial, between-language, and within-language primes produced comparable effects of semantic facilitation. These results are in line with the hypothesis that lexical items in different languages and pictures are processed by means of an amodal conceptual system.


Efficacy of caspofungin in invasive candidiasis and candidemia--de-escalation strategy.
Candida species constitute the majority of nosocomial fungal pathogens in non-neutropenic patients. Candida infections are still connected with substantial mortality. Recent epidemiological observations indicate a shift to non-albicans species, especially because of a rise of infections caused by C. glabrata, which frequently shows fluconazole-resistance. New therapeutic options like caspofungin, as the first licensed echinocandin, new broad-spectrum azoles, and lipid preparations of amphotericin B emerged in the last decade as efficient alternatives to fluconazole and amphotercin B deoxycholate. In invasive candidiasis, a delayed treatment initiation is associated with an increased mortality, thus risk stratification and empirical therapy strategies become vitally important. This review reflects the efficacy of caspofungin in the treatment of Candida infections, especially in the setting of empirical therapy in critically ill patients, and considers the option of de-escalation to fluconazole.


[Amoxicillin-clavulanic acid in late pregnancy].
In 2001, a clinical trial on prophylactic antibiotics in preterm prelabor rupture of membranes reported an increased risk of necrotizing enterocolitis in newborns whose mothers were given amoxicillin-clavulanic acid before delivery. This study generated concern and reluctance to use this antibiotic in late pregnancy, despite its methodological limitations and the lack of confirmation in 3 studies published between 2001 and 2008. Since then, there have been no original publications on the topic. Therefore, the results available to date do not support an increased risk of necrotizing enterocolitis with the use of amoxicillin-clavulanic acid in late pregnancy. In clinical situations where amoxicillin/clavulanic acid is required, it can be prescribed at any stage of pregnancy, including just before delivery.


Tumor necrosis factor beta gene polymorphisms associated with urinary tract infections after renal transplantation.
We investigated whether tumor necrosis factor (TNF) beta(low) or TNFbeta(high) alleles predicted susceptibility to infection or rejection after renal transplantation. TNFbeta alleles were determined in 137 (ESRD) patients and correlated with urinary tract infections and rejection within 60 days among 75 consecutive renal transplant recipients. TNFbeta low was more prevalent among African-Americans than caucasians (83 vs. 63%, P=0.02). After renal transplantation, patients with TNFbeta low experienced more urinary tract infections (50 vs. 10%, P=0.002). The incidence of TNFbeta low and urinary tract infections were equivalent in patients treated with mycophenolate mofetil/cyclosporine (CsAA) (n=37) versus mycophenolate mofetil/tacrolimus (n=38). TNFbeta low was not associated with the incidence of delayed graft function (5 vs. 2, P=NS), early rejection (21 vs. 18%, P=NS) or actuarial 1-year graft survival (96 vs. 90%, P=NS). TNFbeta low was associated with urinary tract infections and TNFbeta high was associated with freedom from urinary tract infections. Neither gene correlated with rejection or l-year graft survival.


Gene therapy for Wiskott-Aldrich Syndrome-Long-term reconstitution and clinical benefits, but increased risk for leukemogenesis.
Wiskott-Aldrich-Syndrome (WAS) is a rare X-linked recessive disease caused by mutations of the WAS gene. It is characterized by immunodeficiency, autoimmunity, low numbers of small platelets (microthrombocytopenia) and a high risk of cancer, especially B cell lymphoma and leukemia.


An evaluation of the NR-1000F Auto Refractometer in high refractive errors.
The manifest refractions of 37 high myopic and 16 high hypermetropic eyes in a total of 28 patients, aged 5 to 42 years, were determined on the Nikon NR-1000F Auto Refractometer. The data obtained were compared with the final clinical prescriptions for these eyes and analysed for degree of agreement for the spherical equivalents, sphere components, and cylinder powers and axes. The Auto Refractometer recordings for all the different refractive components were observed to skew towards more minus in the high myopic eyes but more plus in the high hypermetropes. The possible significance of these skewing patterns is discussed with reference to our earlier studies.


Botulinum Toxins and Zinc: From Theory to Practice-A Systematic Review.
The aims of this study were to determine whether zinc supplementation affects botulinum toxin's effect and longevity and to establish a transition from the molecular to the clinical aspect. We conducted a systematic review in which we included all published studies on PubMed and Embase using the combination of the following terms: "zinc" AND (botox OR botulinum OR onabotulinumtoxinA OR abobotulinumtoxinA OR incobotulinumtoxinA). From the 260 yielded articles, 3 randomized control trials and 1 case report were retained. Three of them found a significant improvement with zinc supplementation in the toxin's effect and longevity. This was observed in neurological conditions and cosmetic uses. Zinc supplementation could be an interesting asset in the potentialization of botulinum neurotoxin effect and longevity. Larger clinical trials and objective measurement tools should be used to further defining the role of zinc in maximizing botulinum neurotoxin effect.


Raman spectroscopic study of ancient South African domestic clay pottery.
The technique of Raman spectroscopy was used to examine the composition of ancient African domestic clay pottery of South African origin. One sample from each of four archaeological sites including Rooiwal, Lydenburg, Makahane and Graskop was studied. Normal dispersive Raman spectroscopy was found to be the most effective analytical technique in this study. XRF, XRD and FT-IR spectroscopy were used as complementary techniques. All representative samples contained common features, which were characterised by kaolin (Al2Si2O5(OH)5), illite (KAl4(Si7AlO20)(OH)4), feldspar (K- and NaAlSi3O8), quartz (alpha-SiO2), hematite (alpha-Fe2O3), montmorillonite (Mg3(Si,Al)4(OH)2 x 4.5 5H(2)O[Mg]0.35), and calcium silicate (CaSiO3). Gypsum (CaSO4 x 2H2O) and calcium carbonates (most likely calcite, CaCO3) were detected by Raman spectroscopy in Lydenburg, Makahane and Graskop shards. Amorphous carbon (with accompanying phosphates) was observed in the Raman spectra of Lydenburg, Rooiwal and Makahane shards, while rutile (TiO(2)) appeared only in Makahane shard. The Raman spectra of Lydenburg and Rooiwal shards further showed the presence of anhydrite (CaSO4). The results showed that South African potters used a mixture of clays as raw materials. The firing temperature for most samples did not exceed 800 degrees C, which suggests the use of open fire. The reddish brown and grayish black colours were likely due to hematite and amorphous carbon, respectively.


Chorea-like symptoms and high blood concentration of ceftriaxone in a patient undergoing hemodialysis: A case report.
Ceftriaxone (CTRX) is a third-generation cephalosporin commonly used to treat infections such as community-acquired pneumonia and urinary tract infections caused by mainly Gram-negative bacteria and some Gram-positive bacteria. Here, we report a case of a patient on hemodialysis who had chorea-like symptoms with high blood concentration of CTRX. A 74-year-old Japanese woman receiving hemodialysis was admitted with obstructive cholangitis and was started on CTRX therapy at a dose of 2 g every 24 hours. On the 6th day after starting administration of CTRX, chorea-like symptoms appeared. We suspected that her symptoms were caused by a high blood concentration of CTRX. We performed a series of blood sampling to determine the concentration of CTRX at different time points before and after discontinuing CTRX administration. CTRX concentrations were higher than those expected in healthy adults, and her chorea-like symptoms had disappeared from the second day of discontinuation of CTRX. The association between CTRX blood concentration and chorea-like symptoms is unclear. However, measuring a series of plasma or serum concentrations from symptom onset to disappearance suggested that chorea-like symptoms appeared when the concentration exceeded approximately 450 μg/mL. Care should be taken when administering CTRX to patients with cholestasis undergoing hemodialysis, as blood CTRX levels may rise unexpectedly and result in complications.


Does platform type matter? A semantic analysis of user attitude formation on online platforms.
An online platform is a setting where users may express their attitude in text or visual content. The doctrine thinking in consumer psychology is that greater perceived product value (e.g., more product features or lower price) gives more positive consumer attitude. Because of different types of platforms, however, online users might form their product/brand attitudes in different ways. We gathered 7,264 lines of online reviews about two famous brands on two types of social media platforms: online text-based forums and live-streaming platforms. The data were collected through a web crawler, and semantic analysis was employed to process the data before hypothesis testing. The findings of this study indicate that users' perception of product features, price levels and brand culture significantly influence user attitude. The more product characteristics communicated on online platforms, the more difficult to formulate a positive user attitude, and users tend to have more positive attitude with higher perceived price. Compared with traditional text-based platforms, contents in live-streaming platforms (e.g., Tik Tok) with less product features, wider culture distance and lower perceived price are favored among users.


Identification of Mycobacterium species in FFPE granulomatous lymphadenitis tissue using REBA Myco-ID®.
Tuberculous lymphadenitis is the most common form of lymphadenopathy; its main histopathological finding is granulomatous inflammation. A reverse blot hybridisation assay, REBA Myco-ID®, was applied to formalin-fixed paraffin-embedded (FFPE) tissue showing granulomatous lymphadenitis to define the causative agents. A total of 119 granulomatous lymphadenitis cases observed between 2000 and 2010 were studied. All tissue samples were treated by haematoxylin and eosin and Ziehl-Neelsen stain. Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) were identified using the REBA Myco-ID assay, and resistance to rifampicin (RMP) and isoniazid (INH) was determined using REBA MTB-MDR®. Of the 119 cases, 113 (95%) were positive with the REBA Myco-ID assay, while 20 (16.8%) were positive on acid-fast bacilli smear. Of the 113 positive REBA Myco-ID cases, 110 (92.43%) were identified as M. tuberculosis, 2 (1.7%) as NTM, and 1 (0.8%) as co-infection with M. tuberculosis and M. chelonae. Only 1 (0.9%) of the 110 M. tuberculosis cases was identified as RMP-resistant. REBA Myco-ID is a highly sensitive and specific assay for detecting M. tuberculosis and NTM. M. tuberculosis is the main cause of granulomatous lymphadenitis.


The effects of land use change on mercury distribution in soils of Alta Floresta, Southern Amazon.
This study presents the spatial distribution, degree of contamination and storage capacity of Hg in surface forest and pasture soils from Alta Floresta, Southern Amazon, a significant gold mining site from 1980 to 1996. During that period, average annual gold production was about 6.5 tons, with an estimated Hg annual emission to the environment of about 8.8 tons, 60-80% of it being emitted to the atmosphere. Mercury sources to the region are mining sites and gold-dealer shops at the city of Alta Floresta, where gold is smelted and commercialized. Mercury concentrations in forest soils (15-248 ng g(-1), average=61.9 ng g(-1)) were 1.5-3.0 times higher than in pasture soils (10-74 ng g(-1), average=33.8 ng g(-1)), suggesting strong re-mobilization after deforestation. Highest Hg concentrations were found within a distance of 20-30 km from mining sites in both soil types. The influence of the refining operations within the city of Alta Floresta, however, was less clear. Somewhat higher concentrations were observed only within a 5 km radius from the city center where gold-dealer shops are located. Wind direction controls the spatial distribution of Hg. Background concentrations (15-50 ng g(-1)) were generally found at the outer perimeter of the sampling grid, about 40 km from sources. This suggests that Hg released from mining and refining activities undergoes rapid deposition. Estimated cumulative Hg burdens for the first 10 cm of soil averaged 8.3 mg m(-2) and 4.9 mg m(-2), for forest and pasture soils respectively and compare well with ultisols and hydromorphic oxisols, but were lower than those found in yellow-red and yellow latosols and podsols from other Amazonian areas. Our results show that changing land use in the Amazon is a strong re-mobilizing agent of Hg deposited on soils from the atmosphere.


Optimal repetition time for free breathing myocardial arterial spin labeling.
The aim of this study was to improve the scan efficiency of ASL in the myocardium. Free breathing FAIR-ASL scans with different TRs were compared, while keeping the acquisition time constant. Scans were named by the trigger pulse that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. TP2 offered the best alternative with a coefficient of variation of 17.15% intrasession and 36.85% intersession. Mean MBF increased by 0.22 ± 0.41 ml/g/min with mild stress.


Lipase nanogel catalyzed synthesis of vitamin E succinate in non-aqueous phase.
In order to improve the stability of vitamin E and broaden its scope of application, an effective solution is to convert vitamin E into its derivatives. This work developed a new Candida rugosa lipase (CRL) nanogel based on modification of ionic liquid with vinyl functional groups. This novel CRL nanogel was used in the preparation process of vitamin E succinate based on the principle of non-aqueous enzymology. At the same time, various factors including enzyme concentration, substrate molar ratio, reaction temperature and reaction time, that affect the yield of vitamin E succinate were optimized and analyzed. Different solvents with various hydrophobicity parameters (LogP values) from -1.3 to 3.5 were studied, it was found that dimethyl sulfoxide (DMSO) had the lowest LogP value among organic solvents but vitamin E succinate had the highest yield in DMSO. Furthermore, the effect of different operating conditions, such as molar ratios of substrate, enzyme concentration, reaction temperature and reaction time was studied. Under the optimal process conditions (enzyme concentration 6 mg mL-1 , substrate molar ratio 4:1, reaction temperature 55 °C and reaction time 15 h), the product yield was 62.58 ± 1.16%. CRL and CRL nanogel were characterized using Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). It was shown that CRL nanogel influenced the catalytic behavior of lipase significantly by changing the structure and surface properties of CRL. Novel lipase nanogel was an excellent biocatalyst for enzymatic synthesis of vitamin E succinate. © 2020 Society of Chemical Industry.


The intricate interplay between HIFs, ROS, and the ubiquitin system in the tumor hypoxic microenvironment.
Alterations in protein ubiquitination and hypoxia-inducible factor (HIF) signaling both contribute to tumorigenesis and tumor progression. Ubiquitination is a dynamic process that is coordinately regulated by E3 ligases and deubiquitinases (DUBs), which have emerged as attractive therapeutic targets. HIF expression and transcriptional activity are usually increased in tumors, leading to poor clinical outcomes. Reactive oxygen species (ROS) are upregulated in tumors and have multiple effects on HIF signaling and the ubiquitin system. A growing body of evidence has shown that multiple E3 ligases and UBDs function synergistically to control the expression and activity of HIF, thereby allowing cancer cells to cope with the hypoxic microenvironment. Conversely, several E3 ligases and DUBs are regulated by hypoxia and/or HIF signaling. Hypoxia also induces ROS production, which in turn modulates the stability or activity of HIF, E3 ligases, and DUBs. Understanding the complex networks between E3 ligase, DUBs, ROS, and HIF will provide insights into the fundamental mechanism of the cellular response to hypoxia and help identify novel molecular targets for cancer treatment. We review the current knowledge on the comprehensive relationship between E3 ligase, DUBs, ROS, and HIF signaling, with a particular focus on the use of E3 ligase or DUB inhibitors in cancer.


Relational technologies as instruments of care in the Family Health Strategy.
This article aims to identify the relational technologies used by Family Health Strategy nurses in their daily work when treating patients. Descriptive and cross-sectional study with qualitative approach; conducted between May and July 2015, in three Basic Health Units of the Southern Region of the Municipality of São Paulo, with 19 nurses of the Family Health Strategy. Data were collected through a semi-structured interview, and the speeches were fully transcribed and analyzed according to the technique of content analysis. From the speeches of the participants, three categories emerged, showing the unawareness of the concept, but the valorization of its use; which are the relational technologies used by the participating nurses (communication, listening, empathy and welcoming reception), as well as the report of barriers to the use of relational technologies. Although the nurses value the use of relational technologies, the participants denoted unawareness of the nomenclature and its associated concepts, suggesting superficiality in the understanding and use of these instruments in the context of care in the Family Health Strategy. Identificar as tecnologias relacionais utilizadas por enfermeiros de Estratégia Saúde da Família em seu cotidiano de trabalho no atendimento aos usuários. Estudo descritivo, transversal, com abordagem qualitativa; desenvolvido entre maio e julho de 2015, em três Unidades Básicas de Saúde da Região Sul do Município de São Paulo, com 19 enfermeiros da Estratégia Saúde da Família. Os dados foram coletados por meio de entrevista semiestruturada, e os discursos foram transcritos na íntegra, analisados segundo a técnica de análise de conteúdo. Das falas dos participantes, surgiram três categorias, que evidenciam o desconhecimento do conceito, mas valorização do uso; quais são as tecnologias relacionais utilizadas pelos enfermeiros participantes (comunicação, escuta, empatia e acolhimento), além do relato de barreiras para a utilização de tecnologias relacionais. Embora valorizem a utilização de tecnologias relacionais, os participantes denotaram desconhecer a nomenclatura e os conceitos associados, sugerindo superficialidade na compreensão e utilização dessas ferramentas no contexto de atendimento na Estratégia Saúde da Família.


Diversity oriented one-pot three-component sequential synthesis of annulated benzothiazoloquinazolines.
Annulated benzothiazoloquinazolines have been synthesized by a diversity oriented simple and convenient synthesis involving one-pot three-component reaction of substituted 2-aminobenzothiazoles with α-tetralone and aromatic/heteroaromatic aldehydes in ethanol in the presence of catalytic amount of triethylamine. The synthesized compounds have been characterized by their elemental analyses and spectral data.


Raver2, a new member of the hnRNP family.
Raver2 was identified as a novel member of the hnRNP family based on sequence homology within three RNA recognition motifs and its general domain organization reminiscent of the previously described raver1 protein. Like raver1, raver2 contains two putative nuclear localization signals and a potential nuclear export sequence, and also displays nucleo-cytoplasmic shuttling in a heterokaryon assay. In glia cells and neurons, raver2 localizes to the nucleus. Moreover, the protein interacts with polypyrimidine tract binding protein (PTB) suggesting that it may participate in PTB-mediated nuclear functions. In contrast to ubiquitously expressed raver1, raver2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is essentially restricted to brain, lung, and kidney in the adult mouse.


Hepatitis A and parvovirus B19 infections in an infant with fulminant hepatic failure.
Acute viral hepatitis with hepatitis A, B, C, D, and E viruses in the etiology of fulminant hepatic failure either single or in combinations has been described. Parvovirus B19 is also an etiologic agent of acute liver failure and hepatitis-associated aplastic anemia. We present a patient diagnosed with fulminant hepatitis A referred for liver transplantation. Parvovirus B19 superinfection was detected when the patient developed anemia during the course of the disease. We discuss possible roles of both viruses in fulminant hepatitis and pure red cell aplasia.


Blockage of HGF/c-Met system by gene therapy (adenovirus-mediated NK4 gene) suppresses hepatocellular carcinoma in mice.
Hepatocyte growth factor promotes cancer development through cell motility-promoting and angiogenic effects. NK4, a fragment of hepatocyte growth factor, acts as its receptor antagonist. We assessed effects of NK4 gene therapy against human hepatocellular carcinoma cells (HUH7) transplanted into mice. NK4 gene transduction was mediated by adenovirus (AdCMV.NK4). LacZ expression adenovirus (AdCMV.LacZ) was used as a control. NK4 effects on HUH7 cells first were studied in vitro. Subcutaneous HUH7 tumors established in athymic nude mice were injected with AdCMV.NK4 (n=6) or AdCMV.Lacz (n=6). Finally, after HUH7 cells were injected into the portal vein in mice with severe combined immunodeficiency to establish hepatic tumors, mice systemically were injected with AdCMV.NK4 (n=6) or AdCMV.LacZ (n=6). NK4 inhibited hepatocyte growth factor-induced phosphorylation of c-Met in HUH7 cells. Invasion and migration of HUH7 cells were inhibited by NK4 transfection, which also suppressed growth of transplanted subcutaneous and liver tumors (p<0.001, p<0.01 respectively), and improved mouse survival (p<0.05). Angiogenesis assessed by small vessel density was significantly decreased in the NK4-treated group. NK4 inhibited tumor cell motility and angiogenesis, greatly suppressing growth of HUH7 tumors transplanted into mouse liver. NK4 gene therapy thus showed apparent promise for treatment of hepatocellular carcinoma.


Development and evaluation of canine reference genes for accurate quantification of gene expression.
In determining relative gene expression by quantitative measurements of mRNA levels using real-time quantitative PCR, internal standards such as reference genes are essential. Large-scale studies evaluating (candidate) reference genes for veterinary research have not been conducted as thoroughly as for human research, although they are equally important. Our goal was to design and evaluate a genome-wide panel of reference genes from different functional classes. First, primers were optimized using mRNA from canine cell lines and from 30 tissues of one dog as template and SYBR green as fluorescent probe. Second, the expression variation and stability of a gene within one specific tissue were determined. Prostate, kidney, mammary gland, left ventricle, and liver tissues from five to nine dogs of different breeds, sexes, ages, body weights, and disease status were used. Averaging relative stabilities over these tissues revealed the usefulness of individual genes as reference genes. Furthermore, according to expression variation of a reference gene within a specific tissue, usually two to four reference genes are sufficient. Taken together, ribosomal protein S19 (RPS19), ribosomal protein S5 (RPS5), beta-2-microglobulin (B2M), and hypoxanthine phosphoribosyltransferase (HPRT) are advocated. However, the optimal set of reference genes depends on the tissue and should be selected and evaluated for each series of experiments.


Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC.
One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.


[Nicorandil-induced cutaneous ulceration on a pacemaker implantation wound].
Nicorandil is a potassium-channel activator used to prevent angina. While mucosal ulceration is a well-known adverse effect of this drug, skin ulcers have been described only rarely, and always in association with mucosal ulcers. An 86-year-old woman presented ulceration on a pacemaker implantation scar despite complete initial wound healing. Nicorandil had been initiated three months earlier. None of the usual causes of ulceration of a pacemaker scar were seen. Complete and permanent wound-healing was achieved 12 days after discontinuation of nicorandil. This is the first reported case of cutaneous ulceration on a vulnerable area of skin ascribable to high-dose nicorandil.


Rat pancreatic interlobular duct epithelium: isolation and culture in collagen gel.
Interlobular duct fragments from the pancreas of the rat were isolated by collagenase digestion and filtration, embedded in a matrix of rat-tail collagen, and cultured in a 1:1 mixture of Dulbecco's minimal essential and Ham's F12 media supplemented with cholera toxin (CT, 100 ng/ml) and epidermal growth factor (EGF, 10 ng/ml) in addition to supplements used previously, thereby improving the yield of ducts by a factor of two compared with previous results. The ducts were harvested by digestion of the collagen matrix with collagenase and were then dissociated by treatment with EDTA in divalent cation-free salt suspended in collagen and cultured as were the ducts. Numerous cysts appeared as a function of time and some of these enlarged dramatically. Some of the larger cysts exhibited secondary tubular processes extending into the surrounding collagen. The addition of bovine pituitary extract (BPE, 50 micrograms/ml) doubled the number of cysts, whereas omission of serum or CT + EGF reduced the number. BPE or forskolin could substitute effectively for CT. Agents that stimulate (secretin) or inhibit (e.g., ouabain or acetazolamide) fluid-electrolyte secretion in vivo had no effect on the number or average diameter of the cysts. The cysts were 83 to 88% epithelial with the balance of the cells being fibroblastic in appearance. Some cysts consisted only of epithelium. The proliferative capacity of the cystic epithelium was shown by the presence of mitotic figures and by an autoradiographic labeling index of 22 to 30% after a 24-h exposure to [3H]thymidine. The labeling index was reduced by the omission of CT + EGF. Transmission electron microscopy showed that the cysts exhibited morphologic features of duct epithelium in vivo, including apical microvilli, lateral interdigitations of the plasma membrane, and typical cytoplasmic organelles.


[Posthaemorrhagic hydrocephalus and periventricular cerebral atrophy in preterm infants with birth weights of 1,500 gm or less. Determination of incidence by brain ultrasound].
Real time ultrasound examinations were performed on 80 consecutive born and surviving infants whose birth weights were 1,500 gm or less. Prior to discharge from the hospital 8 children were shown to have morphologic abnormalities caused by cerebral ischaemia or intraventricular haemorrhage. 6 children (7.5%) had non-progressive enlargement of parts of the ventricular system. 2 children (2.5%) developed a post haemorrhagic hydrocephalus. In one case ventriculostomy was performed, the other had spontaneous arrest. Ultrasound examination of the infant's brain is an ideal screening method to identify children at risk for later development.


Genome-wide identification and comparative in-silico characterization of β-galactosidase (GH-35) in ascomycetes and its role in germ tube development of Aspergillus fumigatus via RNA-seq analysis.
β-galactosidase (Lactase), an enzyme belonging to the glycoside hydrolase family causing the hydrolysis and trans-glycosylation of β-D-galactosides, has a vital role in dairy industries. The current investigation emphasizes on in-silico identification and comparative analysis of different fungal lactases present in Aspergillus fumigatus, Aspergillus oryzae, Botrytis cinerea, and Fusarium fujikuroi. Prediction of motifs and domains, chromosomal positioning, gene structure, gene ontology, sub-cellular localization and protein modeling were performed using different bioinformatics tools to have an insight into the structural and functional characteristics of β-galactosidases. Evolutionary and homology relationships were established by phylogenetic and synteny analyses. A total of 14 β-gal genes (GH-35) were identified in these species. Identified lactases, having 5 domains, were predicted to be stable, acidic, non-polar and extracellularly localized with roles in polysaccharide catabolic process. Results showed variable exonic/intronic ratios of the gene structures which were randomly positioned on chromosomes. Moreover, synteny blocks and close evolutionary relationships were observed between Aspergillus fumigatus and Aspergillus oryzae. Structural insights allowed the prediction of best protein models based on the higher ERRAT and Q-MEAN values. And RNA-sequencing analysis, performed on A. fumigatus, elucidated the role of β-gal in germ tube development. This study would pave the way for efficient fungal lactase production as it identified β-gal genes and predicted their various features and also it would provide a road-way to further the understanding of A. fumigatus pathogenicity via the expression insights of β-gal in germ tube development.


Prevention of radiation-induced liver toxicity after interstitial HDR brachytherapy by pentoxifylline and ursodeoxycholic acid: patient compliance and outcome in a randomized trial.
To investigate the impact of pentoxifylline (PTX, 3 × 400 mg per day) and ursodeoxycholic acid (UDCA, 3 × 250 mg per day) administered for 12 weeks on radiation-induced liver toxicity. Inclusion criteria were liver metastases of extrahepatic malignancies undergoing HDR-BT. 36 patients were prospectively randomized to the medication (N = 18) or control arm (N = 18) and follow-up by hepatobiliary magnetic resonance imaging (MRI) was scheduled 6 and 12 weeks after local ablation by HDR-BT. We determined the threshold doses of fRILI by image fusion of MRI with the dosimetry data. 32 patients completed the study schedule. Per-protocol treatment was limited to 8 patients in the medication group and 16 patients in the control group. 22 adverse events of any grade likely or certainly related to PTX were recorded in 12 patients leading to the discontinuation of the study medication in 7 patients and to a dose reduction of PTX in 2 patients. In the per-protocol population, statistical analysis failed to prove a reduction of fRILI 6 and 12 weeks after HDR-BT. The incidence of adverse effects attributed to PTX (70.6%) was well above the data found in the literature for its approved indication. The study endpoint was not met mainly attributed to the low statistical power of the small per-protocol cohort. Independently, PTX cannot be recommended for the reduction of radiation-induced liver toxicity in oncologic patients undergoing HDR-BT of liver metastases. Further studies might focus on a combination of UDCA with other potential drugs to help establish a preventive and tolerable regimen.


A ligand-independent integrin β1 mechanosensory complex guides spindle orientation.
Control of spindle orientation is a fundamental process for embryonic development, morphogenesis and tissue homeostasis, while defects are associated with tumorigenesis and other diseases. Force sensing is one of the mechanisms through which division orientation is determined. Here we show that integrin β1 plays a critical role in this process, becoming activated at the lateral regions of the cell cortex in a ligand-independent manner. This activation is force dependent and polar, correlating with the spindle capture sites. Inhibition of integrin β1 activation on the cortex and disruption of its asymmetric distribution leads to spindle misorientation, even when cell adhesion is β1 independent. Examining downstream targets reveals that a cortical mechanosensory complex forms on active β1, and regulates spindle orientation irrespective of cell context. We propose that ligand-independent integrin β1 activation is a conserved mechanism that allows cell responses to external stimuli.


Myeloproliferative disorders.
Myeloproliferative disorders result from monoclonal proliferation of the pluripotential hematic precursor cell, with preservation of its capacity to differentiate and mature into functional progeny. Phenotypic expression varies with the degree of involvement of each derivative cell type and the extent to which growth is hyperplastic, dysplastic, or malignant. Hyperplastic bone marrow with increased circulating erythrocytes and platelets, reactivation of hematopoiesis in long bones and extramedullary sites, and the development of secondary marrow fibrosis are responsible for complications of thrombosis, hemorrhage, splenic infarction, hypersplenism, and anemia. A predilection for the geriatric population, chronicity, and great variability in phenotypic expression present a challenge in diagnosis and management. Individualized treatment based on thorough understanding of the pathophysiology of myeloproliferative disease is required to maximize complication-free survival by avoiding both the risk of the disease and its therapy and utilizing all available supportive measures in the prevention and treatment of complications.


[Improvement of excretory urography with the routine use of tomography (author's transl)].
The additional use of routine tomography during excretory urography in our experience has led to a significant improvement in urographic diagnosis. Tomography has provided more diagnostic studies, it also has demonstrated tumors which would have remained undetected with the use of conventional urography alone. This applies particularly to small hypernephromas of stage A, which should be considered as curable.


Effect of basal luteinizing hormone (bLH) level on in vitro fertilization/intra-cytoplasmic injections (IVF/ICSI) outcomes in polycystic ovarian syndrome (PCOS) patients.
To evaluate the effect of basal luteinizing hormone (bLH) levels on In Vitro Fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) outcomes in polycystic ovary syndrome (PCOS). A total of 256 PCOS patients who underwent IVF/ICSI treatment in our center from January 2018 to January 2022 were analyzed retrospectively. The patients were based on the third quartile (12.455) of the basal LH value was taken as the cut-off value and was divided into high and low LH group: high LH group (LH ≥ 12.455 IU / L) and low LH group (LH < 12.455 IU / L) and the OC group was pretreated with oral contraceptives. The outcomes in ovulation induction and embryo transfer cycles of the three groups were then compared. In addition, factors influencing the number of good quality embryos and the early onset LH peak were analyzed. Ages, infertility duration, body mass index (BMI), and basal follicle-stimulating hormone (FSH), and progesterone (P), testosterone (T) levels were not significantly different among the three groups (p > 0.05). However,there were significant differences in basal LH and basal E2 between low LH group and high LH group, and there were significant differences in basal LH between high LH group and OC group (p < 0.05). LH on the antagonist day was significantly different between low LH group and high LH group and between high LH group and OC group (p < 0.05). LH on the hCG (human Chorionic Gonadotropin) day there were significant differences between low LH group and OC group, high LH group and OC group (p < 0.05). The Mode of triggering between the three groups had significant differences between the two groups (p < 0.05). In addition, the number of days from gonadotropin (Gn) initiation to antagonist addition were significantly different among the three groups (p < 0.05). In addition, total Gn doses,the number of oocytes retrieved, the number of Gn days, 2pronucleus (2PN) numbers, number of good quality embryos, and number of high risk OHSS (Ovarian Hyper-stimulation Syndrome), cases with OHSS occurrences were not significantly different among the three groups (p > 0.05). Moreover, the cycle and clinical pregnancy outcomes and the cumulative clinical pregnancy rate and the cumulative live birth rate were not significantly different among the three groups (p > 0.05). LH levels on the day of antagonist addition affected the number of good-quality embryos (B < 0, p < 0.05). However, LH levels on the day antagonist was added were not significantly correlated with basal LH levels (Pearson correlation coefficient = 0.259), the ROC curve was constructed for the logistic prediction model of the early onset LH peak, and the AUC value was 0.747, indicating that the logistic combined model we constructed had a good ability to predict the early onset LH peak. Basal LH levels do not affect the pregnancy outcomes in PCOS patients after antagonist protocols. Besides, LH levels on the day of antagonist addition affect the number of good quality embryos for PCOS patients undergoing IVF /ICSI.


Successive crystal structure snapshots suggest the basis for MHC class I peptide loading and editing by tapasin.
MHC-I epitope presentation to CD8+ T cells is directly dependent on peptide loading and selection during antigen processing. However, the exact molecular bases underlying peptide selection and binding by MHC-I remain largely unknown. Within the peptide-loading complex, the peptide editor tapasin is key to the selection of MHC-I-bound peptides. Here, we have determined an ensemble of crystal structures of MHC-I in complex with the peptide exchange-associated dipeptide GL, as well as the tapasin-associated scoop loop, alone or in combination with candidate epitopes. These results combined with mutation analyses allow us to propose a molecular model underlying MHC-I peptide selection by tapasin. The N termini of bound peptides most probably bind first in the N-terminal and middle region of the MHC-I peptide binding cleft, upon which the peptide C termini are tested for their capacity to dislodge the tapasin scoop loop from the F pocket of the MHC-I cleft. Our results also indicate important differences in peptide selection between different MHC-I alleles.


Advanced training in interventional psychiatry.
Interventional Psychiatry is an emerging subspecialty that treats patients with disorders resistant to routine measures by employing advanced treatment modalities and procedures that require expertise beyond the training provided in a general psychiatric residency. Interventional psychiatrists thus require advanced technical, psychiatric, and general medical training and expertise to be able to provide these treatments in a safe and effective manner. In this article, we will discuss our take on the definition of interventional psychiatry, review the modalities included in this field, and suggest training requirements for an interventional psychiatrist. We will also share our experience in providing advanced interventional psychiatry training as a chief residency or fellowship at the Yale New Haven Psychiatric Hospital.


Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids.
Agonists acting at subtypes of glutamate receptors, N-methyl-D-aspartate, kainate and quisqualate, induce convulsions in rodents. Clonic seizures induced in mice by intracerebral administration of N-methyl-D-aspartate, kainate or quisqualate were used to study the anti- and proconvulsant potential of antiepileptic drugs and beta-carbolines. Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate. In contrast, diazepam blocked convulsions induced by either excitatory amino acid, as did valproate. The benzodiazepine receptor agonist beta-carboline ZK 93423 blocked convulsions induced by kainate but had no effect on seizures induced by N-methyl-D-aspartate or quisqualate. The antagonist beta-carboline ZK 93426 did not affect convulsions induced by excitatory amino acids, while the inverse agonists FG 7142 and ethyl-beta-carboline-3-carboxylate increased the sensitivity of mice to kainate. Phenobarbital and 2-chloroadenosine protected mice against seizures induced by quisqualate and kainate, while baclofen was active against convulsions produced by kainate. MK-801 selectively blocked convulsions induced by N-methyl-D-aspartate, and enhanced the susceptibility of mice to seizures triggered by kainate and quisqualate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate and had little or no effect on other types of seizures. Diphenylhydantoin enhanced the convulsant potential of quisqualate. Trimethadione and carbamazepine did not affect convulsions induced by N-methyl-D-aspartate, kainate or quisqualate. Intracerebral administration of midazolam protected mice against seizures induced by kainate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate, while diphenylhydantoin to quisqualate convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)


[Fish by-products oil corrects dyslipidemia, improves reverse cholesterol transport and stimulates paraoxonase-1 activity in obese rat].
To valorize fish by-products oil by investigating its effects on dyslipidemia, hyperglycemia, reverse cholesterol transport and paraoxonase-1 activity in obese rat. Sixteen male Wistar rats were fed a high fat diet. At 400 ± 10 g, obese rats were randomly divided into two groups: the first received 20% of sardine by-products oil and the second 20% of the edible portion oil. At d28, glycemia and serum lipids concentrations were estimated. High density lipoproteins (HDL2 and HDL3) were separated and their contents and composition in lipids and apolipoproteins were analyzed. Lecithin: cholesterol acyltransferase and paraoxonase-1 activities were assessed. In group which consumed sardine by-products oil, serum cholesterol and triacylglycerols were reduced (-8% and -36%, respectively). However, glycemia was similar. HDL3-phospholipids, HDL3-unesterified cholesterol and HDL3-apolipoproteins were decreased by 56%, 10% and 12%, respectively. Lecithin: cholesterol acyltransferase activity was increased by 35% and the content of HDL2-cholesteryl esters was elevated by 12%. Serum paraoxonase-1 activity was increased by 25%. In obese rat, sardine by-products oil may have a protective effect against cardiovascular risk by improving the anti-atherogenic metabolic pathway of cholesterol and triacylglycerols. This anti-atherogenic action is particularly enhanced by the increase in paraoxonase-1 activity which protects lipoproteins from oxidation.


Stimulatory effect of a pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L., on G-CSF secretion from intestinal epithelial cells.
The inner surface of the intestinal tract possesses a large area of mucosal membranes, and the intestinal epithelial cells exist at the interface between an antigen-rich lumen and a lymphocyte-rich lamina propria. The crosstalk that occurs between these compartments serves to maintain intestinal homeostasis, and the cytokine network plays an important role in the crosstalk. In this study, the effect of a pectic polysaccharide, bupleuran 2IIc from Bupleurum falcatum L., on cytokine secretion of intestinal epithelial cells was investigated in vitro. When murine normal colonic epithelial cell line MCE301 cells were stimulated with bupleuran 2IIc, the contents of granulocyte colony-stimulating factor (G-CSF) in the conditioned medium were significantly increased in dose- and time-dependent manners. The enhanced G-CSF gene transcription in MCE301 cells by the stimulation of bupleuran 2IIc was observed by RT-PCR. The enhanced G-CSF secretion by bupleuran 2IIc was also observed in C3H/HeJ mice derived primary cultured colonic epithelial cells. Bupleuran 2IIc was digested with endo-(1-->4)-alpha-D-polygalacturonase, and the resulting bupleuran 2IIc/PG-1 ("ramified" region) showed potent G-CSF secretion enhancing activity. The activity of bupleuran 2IIc/PG-1 disappeared after the removal of arabinosyl residues from bupleuran 2IIc/PG-1 by endo-(1-->5)-alpha-L-arabinanase digestion. These results suggest that the "ramified" region (bupleuran 2IIc/PG-1) is the active site for the G-CSF secretion enhancing activity of bupleuran 2IIc, and the arabinan moiety of bupleuran 2IIc/PG-1 plays an important role in expression of the activity.


Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand.
No data currently exist about use of antibiotics to prevent surgical site infections (SSI) among patients undergoing appendectomy in Thailand. We therefore examined risk factors, use, and efficacy of prophylactic antibiotics for surgical site infection SSI among patients with uncomplicated open appendectomy. From July 1, 2003 to June 30, 2004 we conducted a prospective cohort study in eight hospitals in Thailand. We used the National Nosocomial Infection Surveillance (NNIS) system criteria to identify SSI associated with appendectomy. We used logistic regression analysis to obtain relative risk estimates for predictors of SSI. Among 2139 appendectomy patients, we identified 26 SSIs, yielding a SSI rate of 1.2 infections/100 operations. Ninety-two percent of all patients (95% CI, 91.0-93.3) received antibiotic prophylaxis. Metronidazole and gentamicin were the two most common antibiotic agents, with a combined single dose administered in 39% of cases. In 54% of cases, antibiotic prophylaxis was administered for one day. We found that a prolonged duration of operation was significantly associated with an increased SSI risk. Antibiotic prophylaxis was significantly associated with a decreased risk of SSI regardless of whether the antibiotic was administered preoperatively or intraoperatively. Compared with no antibiotic prophylaxis, SSI relative risks for combined single-dose of metronidazole and gentamicin, one-day prophylaxis, and multiple-day antibiotic prophylaxis were 0.28 (0.09-0.90), 0.30 (0.11-0.88) and 0.32 (0.10-0.98), respectively. Single-dose combination of metronidazole and gentamicin seems sufficient to reduce SSIs in uncomplicated appendicitis patients despite whether the antibiotic was administered preoperatively or intraoperatively.


Measurement of resiniferatoxin in serum samples by high-performance liquid chromatography.
A novel and simple method of extraction, separation, identification and quantification of resiniferatoxin (RTX) in serum samples is reported. Human serum and whole blood were treated with acetonitrile to denature proteins, such as orosomucoid, and the soluble fraction was passed through a reversed-phase C18 cartridge. RTX eluted from the cartridge was quantified by high-performance liquid chromatography (HPLC) using a reversed-phase C18 column. Reproducible recovery of RTX and tinyatoxin, an internal standard, from serum was achieved. Isocratic elution with 62% acetonitrile provided a suitable retention time without interfering peaks eluting near the analyte. Therefore, the procedure described provides a useful assay for determination of serum RTX pharmacokinetic parameters.


Effectiveness and Safety of Regorafenib vs. Trifluridine/Tipiracil in Unresectable Colorectal Cancer: A Retrospective Cohort Study.
Compared with the best supportive care, a survival benefit of using regorafenib and trifluridine/tipiracil (TFTD) in patients with colorectal cancer has been shown in previous randomized controlled trials (RCTs). However, there is no RCT or large-scale observational study directly comparing regorafenib and TFTD. We used a nationwide claims database in Japan and compared the effectiveness of regorafenib and TFTD for metastatic colorectal cancer during 2013 to 2018. The patients were divided into 4 groups (regorafenib monotherapy, regorafenib/TFTD: regorafenib followed by TFTD, TFTD monotherapy, and TFTD/regorafenib: TFTD followed by regorafenib). Overall survival (OS) and adverse events were compared between the groups. In a subgroup analysis, we also compared treatment effectiveness between the group in which regorafenib was administered first and the group in which TFTD was administered first. We identified 7279 patients (regorafenib: 1501, regorafenib/TFTD: 973, TFTD: 3777, and TFTD/regorafenib: 1028). The corresponding median OS was 6.4, 16.4, 10.2, and 16.9 months, respectively. A log-rank test showed significant intergroup differences (P < .001). In the subgroup analysis, the group in which TFTD was administered first showed significantly longer OS. The incidences of most adverse events were the lowest in the TFTD group. The TFTD group showed longer OS than the regorafenib group, and sequential drug use resulted in the most prolonged OS. Our findings indicate that it might be better to prescribe TFTD first. Furthermore, owing to the longer OS than monotherapy, sequential administration of regorafenib and TFTD ought to be considered.


Determination of organic acids in sugar cane process juice by high-performance liquid chromatography: improved resolution using dual Aminex HPX-87H cation-exchange columns equilibrated to different temperatures.
The application of high-performance liquid chromatography to the quantitative analysis of organic acids in sugar cane process juice is described. Separation of these acids is achieved on Aminex HPX-87H cation-exchange columns. Resolution is improved by connecting two columns in series and equilibrating them at different temperatures. The acids in the sample are first isolated on DEAE-Sephadex A-25 anion-exchange resin equilibrated with 0.5 M isobutyric acid. They are then eluted with 0.5 M sulphuric acid and injected directly onto the HPLC column after filtration through a 0.45-micron membrane. This method allows the simultaneous determination of oxalic, cis-aconitic, citric, phosphoric, malic, trans-aconitic, succinic, glycolic, lactic, formic and acetic acids. Isobutyric acid is also separated on this system and provides a useful guide to the loading capacity of the anion-exchange resin.


Green space exposure and colorectal cancer: A systematic review.
Green space has been linked to colorectal cancer, but the evidence is still limited and inconclusive. This review aimed to investigate the relationship between green space and CRC. The studies were searched using three primary journal databases: PubMed, Scopus, and Web of Science. The retrieved citations were screened, and data from articles about GS exposure and CRC were extracted. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was used to evaluate the studies' quality. Five of the 1792 articles identified were eligible for the final review, which included five cohort studies published between 2017 and 2022. Each one article from the United States, the United Kingdom, France, Belgium, and Germany and All studies are of high quality. Four studies reported CRC incidence and one study reported CRC mortality from GS exposure. There was no significant association between GS attributes (Normalized Difference Vegetation Index (NDVI), surrounding greenness, surrounding green area, proximity to GS (agricultural lands, urban GSs, and forests), and count of recreational facilities and parks) with CRC. Only one study discovered that a healthier ecosystem was linked to a lower CRC risk. Although the evidence is still limited, the findings may indicate the presence of other factors in the relationship between GS and CRC. Future research should continue to focus on the variation of GS and the factors that influence it. Specific attention to the development of GS has the potential to produce benefits while mitigating cancer risk.


Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of alpha6beta1 integrin.
Peritoneal dissemination of ovarian carcinoma is mediated by epithelial-mesenchymal interconversions leading to the disruption of cell-cell contact and modulation of cell-extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in alpha2, alpha6 and beta1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of alpha6 and beta1 integrin subunits. Neutralizing antibodies against alpha6 and beta1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of alpha6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of alpha6beta1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475-85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and alpha6beta1 integrin-mediated signalling in ovarian carcinomas.


Modulation of SERCA2 activity: regulated splicing and interaction with phospholamban.
Ca(2+)-uptake into intracellular stores is mediated by the sarco/endoplasmic reticulum Ca(2+)ATPases (SERCAs). This review deals first with the gene structural and the characterization of the tissue-specific SERCA2 transcript processing. Secondly, the two different protein isoforms and their regulation are described. Finally, this review ends with a discussion on the possible physiological role of the SERCA2 isoform diversity.


Combination of EGFR and COX-2 inhibitors in breast cancer patient.
Ther combination of EGFR and COX-2 inhibitors in breast cancer patient treatment is a topic of interest. In this work, the author discusses on the synergistic effect of concomitant usage of the two drugs and also further notes on the myth in using this combination.


Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?
To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum≤7 (n=134) or Gleason sum≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. The group with a Gleason sum≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum≥8 or the presence of extracapsular invasion.


Leishmaniasis recidiva cutis in American cutaneous leishmaniasis.
Leishmaniasis recidiva cutis (LRC) consists of active lesions around or inside the scar of classical cutaneous leishmaniasis (CL). In the literature it is considered as an hyperergic form of CL because the patients show a strong response to intradermal testing with leishmania antigen and, histologically, the parasites are scarce or absent; a well-organized granuloma is always observed. Three patients from Bahia (Brazil) with LRC were evaluated by clinical examination, biopsies, skin tests with leishmania antigen, serology, and culture. In addition, a specific lymphocyte blastogenesis test was done and the species of leishmania characterized. The disease was caused by both L. amazonensis and L. braziliensis and serological titers varied from 1/16 to 1/64. The patients presented histologic and immunologic aspects different from those referred to in the literature. From four biopsies obtained only two presented a granulomatous reaction and parasites varied from absent to a parasite index 3. In one patient an absence of T cell response to leishmania antigen was observed in the first evaluation with restoration of the response after cure. In the other two, the degree of the specific proliferative response was lower than that usually observed in patients with classical CL. These findings indicate that New World LRC can not be considered a hyperergic form of CL. With respect to its clinical aspects and response to treatment, LRC must be considered as an entity different from the classical CL.


Artificial Stone Silicosis: Rapid Progression Following Exposure Cessation.
Silicosis is rapidly emerging in high-income countries in relation to the replacement of natural stone with artificial stone, especially in the manufacturing and installation of kitchen and bathroom countertops. Progression of this form of silicosis following the cessation of exposure is unknown. The objective of this study was to determine the radiologic progression and lung function in individuals with artificial stone silicosis. Between 2009 and 2018, a total of 106 patients were diagnosed with artificial stone silicosis in the Bay of Cádiz area (southern Spain), 14.15% by using biopsy results and the remainder according to chest radiography and high-resolution CT imaging. Follow-up consisted of respiratory function tests and radiographic studies. All patients stopped working in the stone industry following diagnosis. All patients were men; their mean ± SD age at diagnosis was 36.2 ± 7.0 years, and the mean duration of exposure was 12.0 ± 4.3 years. At diagnosis, 99 patients were considered to have simple silicosis (93.4%) and seven to have progressive massive fibrosis (PMF) (6.6%). After a mean follow-up of 4.01 ± 2.1 years, disease in 56% of patients had progressed two or more International Labour Office subcategories, and the number of patients with PMF had increased to 40 (37.7%). Regarding lung function, there was a decrease in FVC and FEV1, with an average decrease of 86.8 and 83.4 mL per year, respectively; in 25% of patients, the annual decrease was > 157 mL in FVC and > 133 mL in FEV1. Multivariable analysis showed that lower FVC at diagnosis and longer duration of exposure to silica were associated with progression to PMF. Artificial stone silicosis rapidly progresses to PMF even following exposure cessation, and a significant percentage of patients experience a very rapid decrease in lung function.


[The influence of selected plants on the tobacco smoking-induced effects in the oral cavity--review].
Tobacco smoking is a culprit of many pathological lesions on the oral mucosa. In this literature review we focused on various therapeutic options for tobacco induced mucosal pathologies. Many active ingredients of Aloe vera, Chamomile, Curcuma longa and Calendula show potent anti-inflammatory and regenerative activity, making plant derived drugs a reasonable option for traditional pharmaceuticals.


Characteristics of the wideband absorbance of acoustic energy in children (3-7 years old) with otitis media with effusion.
This study aimed to investigate the characteristics of the wideband absorbance (WBA) of acoustic energy in children (3-7 years old) with otitis media with effusion (OME) under environmental ear-canal air pressure and tympanometric peak pressure and to determine the diagnostic value of the acoustic energy absorption rate (AR) in OME at different frequencies. A total of 178 children aged 3-7 years were enrolled in the study between April and October 2018. They were separated into two groups: those with middle ear effusion were placed in the OME group (n = 80; 136 ears), while those without OME (n = 98; 182 ears) were placed in the control group. A WBA test was performed on the children in both groups under environmental ear-canal pressure and tympanometric peak pressure to analyze the changing characteristics of the AR value within the 0.226-8 kHz range. Under ambient ear-canal air pressure, the AR of the OME group in each frequency band was significantly lower than that of the control group (P < 0.01). Under tympanometric peak pressure, the AR of the OME group in most frequencies was also significantly lower than those of the control group (P < 0.01) except in the 2-2.5 kHz range. The area under the receiver operating characteristic curve (AUROC) was highest at 0.47-1.03 kHz: 0.96 and 0.94 at ambient ear-canal pressure and tympanometric peak pressure, respectively. Of the single frequency points, those at 0.65, 0.67, 0.69, 0.71, and 0.73 kHz had a higher AUROC value (0.96-0.97) under both ambient ear-canal air pressure and tympanometric peak pressure. The difference in the AUROC values of the two pressure conditions was not statistically significant (P < 0.01). Overall, WBA is an effective method of diagnosing OME in children. The frequency band with the most predictive value of AR for OME is 0.47-1.03 kHz. Middle ear effusion can be quickly identified by observing AR values in this frequency range, which provides a diagnostic basis for OME.


Nutrient intake and body weight in a large HIV cohort that includes women and minorities.
Evaluate the baseline nutrient intake of an HIV positive population that includes significant representation from women and minorities, and determine the relationship between state of disease and nutritional intake. Baseline data from a prospective study (Nutrition for Healthy Living). Individuals with HIV in the Boston and Rhode Island area (n = 516); 25% were women and 30% were minorities. Nutrient intakes from 3-day food records, which included vitamin/mineral supplements, were estimated by gender and nonwhite vs white categories, after grouping by CD4 lymphocyte counts. Spearman correlation coefficients, Wilcoxon signed rank test, Wilcoxon rank sum test, chi2 test, and restricted cubic spline model were used for data analyses as indicated. Macronutrient but not micronutrient intake was statistically and inversely associated with decreasing CD4 cell counts. The median intake of micronutrients was higher in the study sample compared with the same age and gender group in NHANES III data; however, 25% to 35% of the women in our study sample had dietary intakes of less than 75% of the DRIs for vitamins A, C, E and B-6, and iron and zinc. White men had statistically higher values of all micronutrients compared with nonwhite men. Body mass index for men and women ranged from 23 to 25. Median values for micronutrient intake from food plus vitamin/mineral supplements were adequate in the overall population studied, but a large percent of women and minorities had inadequate nutrient intakes and would benefit from dietary assessment and counseling.


Upgrade of D+ software for hierarchical modeling of X-ray scattering data from complex structures in solution, fibers and single orientations.
This article presents an upgrade of the D+ software [Ginsburg et al. (2019 ▸). J. Appl. Cryst. 52, 219-242], expanding its hierarchical solution X-ray scattering modeling capabilities for fiber diffraction and single crystallographic orientations. This upgrade was carried out using the reciprocal grid algorithm [Ginsburg et al. (2016 ▸). J. Chem. Inf. Model. 56, 1518-1527], providing D+ its computational strength. Furthermore, the extensive modifications made to the Python API of D+ are described, broadening the X-ray analysis performed with D+ to account for the effects of the instrument-resolution function and polydispersity. In addition, structure-factor and radial-distribution-function modules were added, taking into account the effects of thermal fluctuations and intermolecular interactions. Finally, numerical examples demonstrate the usage and potential of the added features.


Muscular dystrophy: diagnosis and treatment.
The clinical signs and symptoms of the most common muscular dystrophies are presented. Plans for treatment and genetic counseling are outlined. A new operation for correction of scapular winging is described with illustrative cases.


Thai ethnomedicinal plants as resistant modifying agents for combating Acinetobacter baumannii infections.
Acinetobacter baumannii is well-recognized as an important nosocomial pathogen, however, due to their intrinsic resistance to several antibiotics, treatment options are limited. Synergistic effects between antibiotics and medicinal plants, particularly their active components, have intensively been studied as alternative approaches. Fifty-one ethanol extracts obtained from 44 different selected medicinal plant species were tested for resistance modifying agents (RMAs) of novobiocin against A. baumannii using growth inhibition assay. At 250 μg/ml, Holarrhena antidysenterica, Punica granatum, Quisqualis indica, Terminalia bellirica, Terminalia chebula, and Terminalia sp. that possessed low intrinsic antibacterial activity significantly enhanced the activity of novobiocin at 1 μg/ml (1/8xminimum inhibitory concentration) against this pathogen. Holarrhena antidysenterica at 7.8 μg/ml demonstrated remarkable resistant modifying ability against A. baumannii in combination with novobiocin. The phytochemical study revealed that constituents of this medicinal plant contain alkaloids, condensed tannins, and triterpenoids. The use of Holarrhena antidysenterica in combination with novobiocin provides an effective alternative treatment for multidrug resistant A. baumannii infections.


Activation of guanylate cyclase from rat liver and other tissues by sodium azide.
Sodium azide, hydroxylamine, and phenylhydrazine at concentrations of 1 mM increased the activity of soluble guanylate cyclase from rat liver 2- to 20-fold. The increased accumulation of guanosine 3':5'-monophosphate in reaction mixtures with sodium azide was not due to altered levels of substrate, GTP, or altered hydrolysis of guanosine 3':5'-monophosphate by cyclic nucleotide phosphodiesterase. The activation of guanylate cyclase was dependent upon NaN3 concentration and temperature; preincubation prevented the time lag of activation observed during incubation. The concentration of NaN3 that resulted in half-maximal activation was 0.04 mM. Sodium azide increased the apparent Km for GTP from 35 to 113 muM. With NaN3 activation the enzyme was less dependent upon the concentration of free Mn2+. Activation of enzyme by NaN3 was irreversible with dilution or dialysis of reaction mixtures. The slopes of Arrhenius plots were altered with sodium azide-activated enzyme, while gel filtration of the enzyme on Sepharose 4B was unaltered by NaN3 treatment. Triton X-100 increased the activity of the enzyme, and in the presence of Triton X-100 the activation by NaN3 was not observed. Trypsin treatment decreased both basal guanylate cyclase activity and the responsiveness to NaN3. Phospholipase A, phospholipase C, and neuraminidase increased basal activity but had little effect on the responsiveness to NaN3. Both soluble and particulate guanylate cyclase from liver and kidney were stimulated with NaN3. The particulate enzyme from cerebral cortex and cerebellum was also activated with NaN3, whereas the soluble enzyme from these tissues was not. Little or no effect of NaN3 was observed with preparations from lung, heart, and several other tissues. The lack of an effect with NaN3 on soluble GUANYLATE Cyclase from heart was probably due to the presence of an inhibitor of NaN3 activation in heart preparations. The effect of NaN3 was decreased or absent when soluble guanylate cyclase from liver was purified or stored at -20degrees. The activation of guanylate cyclase by NaN3 is complex and may be the result of the nucleophilic agent acting on the enzyme directly or what may be more likely on some other factor in liver preparations.


[Microscopical identification of Scolopa chinensis].
To study the microscopical features of Scolopa chinensis. By microscope, the tissue characteristics and the powder characteristics were studied. The results are accurate and practical. These Characteristics can provide evidences for the identifcation of Scolopa chinensis.


Visualization of rat brain receptors for the neuropeptide, substance P.
Biochemical analysis of the binding of [125I]Bolton-Hunter coupled substance P [( 125I]BH-SP) to slide-mounted sections of rat brain demonstrated that [125I]BH-SP labels a binding site with a structure-activity profile characteristic of a substance P receptor. Under optimized preincubation and incubation conditions, the locations of substance P (SP) receptors were visualized by film and emulsion autoradiography. Receptor densities were quantified by computer-assisted densitometry. SP receptors are widely but discretely distributed throughout sensory, limbic and cortical areas of rat brain, though several motor areas also possess SP receptors. No receptors were detected in the substantia nigra and interpeduncular nucleus, which are innervated by SPergic nerves; these regions of the brain may possess a low affinity SP receptor not detectable with this assay. Findings are discussed in the framework of an overall notion of the role of neuropeptides in the biochemistry of emotion.


Focal segmental membranoproliferative glomerulonephritis in children.
Eight patients with focal segmental membranoproliferative glomerulonephritis (FSMPGN) were followed for 5-16 years. Their urinary abnormalities were detected by school urinary screening in seven, and one patient presented with nephrotic syndrome. All but one patient were treated with alternate-day (ALD) prednisolone. With time, urinalysis became normal in six and two continued to have proteinuria with or without hematuria. Serum albumin, cholesterol, and creatinine levels were normal at the last follow-up. Serum C3 returned to normal levels in six, but remained persistently decreased in two. Mesangial proliferation and matrix changes in glomeruli without MPGN lesions were mild. Subendothelial and mesangial electron-dense deposits and deposits containing C3 along capillary walls and mesangium were observed. MPGN lesions and mesangial proliferation improved. No severe growth retardation was observed, but the duration and dosage of ALD prednisolone could be reduced further, since the patients with FSMPGN seemed to have an excellent prognosis.