An improved cytokinin bioassay using cultured soybean hypocotyl sections.
This paper describes a modified soybean (Glycine max) tissue culture bioassay for cytokinins. Soybean hypocotyls were grown under sterile conditions and sliced into 1-mm sections. Sections were cultured for 5,9,13, or 22 days on a callus medium with zeatin or other cytokinins. The fresh weight of sections increased with the cytokinin concentration from 0.0005 to 1 mum zeatin; 2-fold concentration differences were readily distinguishable at 9 days. The assay should prove to have several advantages over the conventional soybean callus bioassay including convenience, lower variability between tissue samples, and improved resolution. Its specificity is comparable to that of the soybean callus bioassay.


Theoretical Exploring of a Molecular Mechanism for Melanin Inhibitory Activity of Calycosin in Zebrafish.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin can lead to a variety of skin disorders. Calycosin is an isoflavone from Astragali Radix, which is a traditional Chinese medicine that exhibits several pharmacological activities including skin whitening. In our study, the inhibitory effect of calycosin on melanin production is confirmed in a zebrafish in vivo model by comparing with hydroquinone, kojic acid, and arbutin, known as tyrosinase inhibitors. Moreover, the inhibitory kinetics of calycosin on tyrosinase and their binding mechanisms are determined using molecular docking techniques, molecular dynamic simulations, and free energy analysis. The results indicate that calycosin has an obvious inhibitory effect on zebrafish pigmentation at the concentration of 7.5 μM, 15 μM, and 30 μM. The IC50 of calycosin is 30.35 μM, which is lower than hydroquinone (37.35 μM), kojic acid (6.51 × 103 μM), and arbutin (3.67 × 104 μM). Furthermore, all the results of molecular docking, molecular dynamics simulations, and free energy analysis suggest that calycosin can directly bind to the active site of tyrosinase with very good binding affinity. The study indicates that the combination of computer molecular modeling and zebrafish in vivo assay would be feasible in confirming the result of the in vitro test and illustrating the target-binding information.


[Simultaneous determination of E-, EAC- und D-rosette-forming cells in peripheral blood of healthy individuals (author's transl)].
By the aid of four different indicator systems E-, EAC- and D-rosette-forming cells in human peripheral blood were investigated. It was demonstrated, that the indicator system consisting of sheep red blood cells and complement-conjugated zymosan particles is the most effectively. Approximately, 60% of lymphocytes form E- and approximately, 13-15% EAC-rosettes. Besides T- and B-lymphocytes in all donors of blood were detected so-called D-lymphocytes. The number of D-lymphocytes ranged from 0,5% to 7%. D-lymphocytes are heterogeneous, evaluated by the number of fixed T- and B-indicator cells on their surface.


A computer-simulated mechanism of familial Alzheimer's disease: Mutations enhance thermal dynamics and favor looser substrate-binding to γ-secretase.
The 4-subunit intramembrane protease complex γ-secretase cleaves many substrates including fragments of the β-amyloid precursor protein (APP), leading to formation of Aβ peptides, and Notch. Mutations in APP and the catalytic subunit of γ-secretase, presenilin, cause familial Alzheimer's disease (fAD). Mutations are assumed to change the substrate-binding and cleavage and thereby the Aβ formed. Whereas a wild-type structure of substrate-bound γ-secretase became recently available from cryogenic electron microscopy (6IYC), the structure and dynamics of mutant proteins remain obscure. Here, we studied five prominent mutants of substrate-bound γ-secretase by explicit all-atom molecular dynamics in a phospholipid membrane model at physiological temperature using the experimental structure as template: The presenilin 1 mutants E280A, G384A, A434C, and L435F and the V717I mutant of APP. Our structures and dynamics provide the first atomic detail into how fAD-causing mutations affect substrate binding to γ-secretase. The pathogenic mutations tend to increase the space and variability in the substrate binding site, as seen e.g. from the distance from catalytic aspartate to substrate cleavage sites. We suggest that we have identified the molecular cause of the "imprecise cleavage" that leads to two trimming pathways in γ-secretase, consistent with the FIST model, which may rationalize the experimental Aβ42/Aβ40 ratios as a molecular basis for fAD.


Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer.
We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR. Progression-free survival and overall survival with EGFR-TKIs treatment were evaluated using Kaplan-Meier methods and compared between different patients using log-rank tests. Twenty-one (6.6%) of 320 EGFR mutant samples with additional gene alterations were identified. The most common concurrent gene was PIK3CA mutation (n = 9), followed by EML4-ALK rearrangement (n = 6), HER2 mutation (n = 3), RET rearrangement (n = 1), ROS1 rearrangement (n = 1) and KRAS mutation (n = 1). Patients with single EGFR mutation had a significantly longer progression-free survival than those with concurrent genes (10.9 vs. 6.0 months, P = 0.002). Among the 21 cases, patients with PIK3CA mutation had the longest median progression-free survival (7.6 months), followed by ALK rearrangement (5.0 months) and other gene types (1.2 months). No overall survival difference was found between patients with single EGFR mutation and concurrent gene alterations (21.0 vs.17.6 months, P = 0.17). We demonstrated that concurrent gene alterations occurred in some patients with EGFR mutations. Concurrent gene alterations decreased the efficacy of EGFR-TKIs.


Complete dentures for the obturator patient.
Treatment of the edentulous obturator patient requires the same basic fundamentals as used in the treatment of the complete-denture patient. Problems and considerations unique to the development, delivery, and follow-up of the complete maxillary obturator prosthesis and mandibular denture in the patient with an acquired maxillary defect are discussed. Combining laboratory and clinical research in maxillofacial prosthodontics and plastic and reconstructive surgery continues to improve the rehabilitation of these patients.


Sustained released of bioactive mesenchymal stromal cell-derived extracellular vesicles from 3D-printed gelatin methacrylate hydrogels.
Extracellular vesicles (EVs) represent an emerging class of therapeutics with significant potential and broad applicability. However, a general limitation is their rapid clearance after administration. Thus, methods to enable sustained EV release are of great potential value. Here, we demonstrate that EVs from mesenchymal stem/stromal cells (MSCs) can be incorporated into 3D-printed gelatin methacrylate (GelMA) hydrogel bioink, and that the initial burst release of EVs can be reduced by increasing the concentration of crosslinker during gelation. Further, the data show that MSC EV bioactivity in an endothelial gap closure assay is retained after the 3D printing and photocrosslinking processes. Our group previously showed that MSC EV bioactivity in this assay correlates with pro-angiogenic bioactivity in vivo, thus these results indicate the therapeutic potential of MSC EV-laden GelMA bioinks.


Composition-Dependent Cytotoxic and Antibacterial Activity of Biopolymer-Capped Ag/Au Bimetallic Nanoparticles against Melanoma and Multidrug-Resistant Pathogens.
Nanostructured silver (Ag) and gold (Au) are widely known to be potent biocidal and cytotoxic agents as well as biocompatible nanomaterials. It has been recently reported that combining both metals in a specific chemical composition causes a significant enhancement in their antibacterial activity against antibiotic-resistant bacterial strains, as well as in their anticancer effects, while preserving cytocompatibility properties. In this work, Ag/Au bimetallic nanoparticles over a complete atomic chemical composition range were prepared at 10 at% through a green, highly reproducible, and simple approach using starch as a unique reducing and capping agent. The noble metal nanosystems were thoroughly characterized by different analytical techniques, including UV-visible and FT-IR spectroscopies, XRD, TEM/EDS, XPS and ICP-MS. Moreover, absorption spectra simulations for representative colloidal Ag/Au-NP samples were conducted using FDTD modelling. The antibacterial properties of the bimetallic nanoparticles were determined against multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, showing a clear dose-dependent inhibition even at the lowest concentration tested (5 µg/mL). Cytocompatibility assays showed a medium range of toxicity at low and intermediate concentrations (5 and 10 µg/mL), while triggering an anticancer behavior, even at the lowest concentration tested, in a process involving reactive oxygen species production per the nanoparticle Au:Ag ratio. In this manner, this study provides promising evidence that the presently fabricated Ag/Au-NPs should be further studied for a wide range of antibacterial and anticancer applications.


Prediction of hematopoietic stem cell yield after mobilization with granulocyte-colony-stimulating factor in healthy unrelated donors.
The collection of hematopoietic stem cells from the peripheral blood of healthy donors has been established as a highly efficient method. Nevertheless, some donors have a moderate or poor chance of harvest success with standard mobilization regimens. We retrospectively reviewed data from 7216 unrelated healthy donors, who underwent granulocyte-colony-stimulating factor mobilization and consecutive leukapheresis for allogeneic stem cell transplantation. We tested different donor variables of potential influence and established a statistical model for prediction of upfront mobilization capacity and harvest success. In addition, we calculated the likelihood of a successful harvest dependent on predicted preapheresis CD34+ count and recipient weight. Female sex, older age, smoking, elevated lactate dehydrogenase, higher relative lymphocyte count, and higher large unstained cell count at baseline were negatively correlated with the CD34+ cell count on Day +5 (p < 0.0001). In contrast, higher platelet count, higher body mass index, higher absolute lymphocyte count, and higher relative monocyte count at baseline showed a positive correlation with the CD34+ count on Day +5 (p < 0.0001). Using a model built on these factors, we could significantly improve the prediction of harvest success compared to a basic model. The model allows the identification of female donors who eventually have a significant risk of harvest failure if requested to donate for recipients with a high body weight.


Intrathecal Morphine Is Associated with Less Delirium Following Hip Fracture Surgery: A Register Study.
Delirium is a common complication after proximal femoral fracture surgery, with pain and opioid consumption as the contributing factors. The administration of intrathecal morphine may decrease these factors postoperatively and potentially reduce delirium. This research aimed to study the association between the use of intrathecal morphine and the occurrence of delirium. A retrospective analysis of a prospective register kept in a non-academic hospital in the Netherlands was performed. The register contained data of all patients with proximal femur fractures that were surgically treated with osteosynthesis or prosthesis. Patients receiving spinal anesthesia (SA group) were compared with patients receiving spinal anesthesia with the addition of intrathecal morphine (SIM group). The administration of either SA or SIM was based on the preference of the anesthesiologist. The primary outcome was the incidence of delirium, as defined by the DSM-V classification. The follow-up lasted until hospital discharge. Both univariate and multivariate analyses were performed. The SA group consisted of 451 patients, and the SIM group included 34 patients. Delirium occurred in 19.7% in the SA group versus 5.9% in the SIM group (P = 0.046). This association remained significant after correction in multivariate analysis (OR of delirium in the SA group, 95% CI: 1.062 - 21.006, P = 0.041). Additionally, multivariate analysis revealed that age, gender, preoperative cognitive impairment, and fracture treatment (osteosynthesis or prosthesis) were independently associated with delirium. This retrospective study found an independent association between the use of intrathecal morphine and a lower incidence of delirium. This clinically relevant decrease in delirium should be studied in a prospective randomized study.


Surgical complications and outcome of pediatric liver transplantation in Hong Kong.
The aim of this study was to analyze the early and late results of pediatric liver transplantation, with particular reference to complications that required surgical or radiologic intervention. The records and code sheets of children who underwent liver transplantation in the authors' institution between September 1993 and December 2001 were reviewed. Twenty-nine children (16 boys and 13 girls) underwent 31 liver transplantations (23 living donor, 8 cadaveric donor) during the study period. The ages of the children ranged from 4 months to 132 months (median, 16 months). Eighteen children had complications that required surgical or radiologic interventional procedures. Complications included, among others, hepatic vein thrombosis (n = 1, 3%), hepatic vein stenosis (n = 2, 7%), portal vein thrombosis (n = 2, 7%), biliary stricture (n = 3, 10%), bile leakage (n = 2, 7%), hepatic artery pseudoaneurysm (n = 1, 3%), jejuno-jejunostomy leakage (n = 1, 3%), graft hepatitis (n = 1, 3%), and posttransplant lymphoproliferative disorder (n = 2, 7%). In addition, 6 children (21%) suffered from intraabdominal bleeding from a variety of causes. After appropriate interventions, at a median follow-up of 38 months (range, 1 to 96 months), patient and graft survival rates were 79% and 74%, respectively. The retransplantation rate was only 7%. There was no incidence of hepatic artery thrombosis. All living donors remain alive and well. Complications are inevitable in pediatric liver transplantation. However, with timely recognition and active intervention, a good outcome can be achieved.


The inflammatory response to miniaturised extracorporeal circulation: a review of the literature.
Conventional cardiopulmonary bypass can trigger a systemic inflammatory response syndrome similar to sepsis. Aetiological factors include surgical trauma, reperfusion injury, and, most importantly, contact of the blood with the synthetic surfaces of the heart-lung machine. Recently, a new cardiopulmonary bypass system, mini-extracorporeal circulation (MECC), has been developed and has shown promising early results in terms of reducing this inflammatory response. It has no venous reservoir, a reduced priming volume, and less blood-synthetic interface. This review focuses on the inflammatory and clinical outcomes of using MECC and compares these to conventional cardio-pulmonary bypass (CCPB). MECC has been shown to reduce postoperative cytokines levels and other markers of inflammation. In addition, MECC reduces organ damage, postoperative complications and the need for blood transfusion. MECC is a safe and viable perfusion option and in certain circumstances it is superior to CCPB.


Postprandial Blood Glucose Outweighs Fasting Blood Glucose and HbA1c in screening Coronary Heart Disease.
The objective of the present study is to assess the performance of fasting blood glucose (FBG), postprandial blood glucose (PBG), and glycated hemoglobin (HbA1c) as screening for coronary heart disease (CHD) in an inpatient population undergoing coronary angiography. 1852 consecutive patients scheduled for coronary angiography were classified into Normal Glucose Tolerance (NGT), Impaired Glucose Regulation (IGR), and diabetes, based on FBG, PBG, and HbA1c. Correlations of Gensini score with glucose metabolism and insulin resistance were analyzed. The associations between glycemic variables and Gensini score or the presence of CHD were analyzed by multiple linear regression and logistic regression, respectively. CHD was diagnosed in 488, 622, and 414 patients with NGT, IGR, and diabetes, respectively. Gensini score was positively correlated with FBG (r = 0.09, p < 0.01), PBG (r = 0.20, p < 0.01), and HbA1c (r = 0.19, p < 0.01). Gensini score was not correlated with fasting insulin (r = -0.081, p = 0.36), post-prandial insulin (r = -0.02, p = 0.61), or HOMAIR (r = -0.0059, p = 0.13). When FBG, PBG and HbA1c were pooled altogether, only PBG persisted in its association with Gensini score and the prevalence of CHD. The severity of CHD was associated with glucose rather than insulin resistance in this Chinese population. PBG was optimally correlated with the presence and severity of CHD.


Microtubules mediate germ-nuclear behavior after meiosis in conjugation of Paramecium caudatum.
Microtubule dynamics in Paramecium caudatum were investigated with an anti-alpha-tubulin antibody and a microinjection technique to determine the function of microtubules on micronuclear behavior during conjugation. After meiosis, all four haploid micronuclei were connected by microtubular filaments to the paroral region and moved close to this region. This nuclear movement was micronucleus-specific, because some small macronuclear fragments transplanted from exconjugants never moved to the region. Only one of the four germ nuclei moved into the paroral cone and was covered by microtubule assembly (the so-called first assembly of microtubules, AM-I). This nucleus survived there, while the other three not in this region degenerated. The movement of germ nucleus was inhibited by the injection of the anti-alpha-tubulin antibody. The surviving germ nucleus divided once and produced a migratory pronucleus and a stationary pronucleus. Prior to the reciprocal exchange of the migratory nuclei, microtubules assembled around the migratory pronuclei again (the so-called second assembly of microtubules, AM-II). Then, the migratory pronucleus moved into the partner cell and fused with the stationary pronucleus. Thus, microtubules appear to be indispensable for nuclear behavior: they enable migration of postmeiotic nuclei to the paroral region and they permit the survival of the nucleus at the paroral cone.


24-h Urine Collection: A Relevant Tool in CKD Nutrition Evaluation.
Dietary management is a cornerstone of Chronic Kidney Disease (CKD) monitoring, and dietary surveys often difficult to perform. We studied in a CKD patient cohort with two years follow-up, whether validated 24-h urine ionogram would be a relevant tool for diet evaluation and compliance. We included 404 non-dialysis CKD patients, with three evaluations, including repeated measurements of fractional renal creatinine clearance and 24-h urine collection. Completeness of the 24-h urine collection, assessed by daily urine creatinine excretion extrapolated from fractional creatinine clearance, was 64.6%, 75.5%, and 78.2% at the first, second, and third visits, respectively. One hundred sixty-eight patients (41.6%) had three complete collections, with a measured glomerular filtration of 42.3 mL/min/1.73 m2 at baseline and prevalence of anemia and secondary hyperparathyroidism of 13.9% and 26.2%, respectively, increasing during follow-up to 15% and 31.5% (p < 0.001 and p < 0.001). The urine analysis showed at baseline a urine volume of above 2 L/day, and estimated sodium and protein intake within targets in 51.6% and 40.3% of cases, which improved during follow-up only for protein (to 45.9%, p < 0.0001). Our data suggest that a 24-h urine ionogram is an interesting, reliable tool in CKD patients for dietary monitoring to achieve target recommendation noteworthy salt and protein intake.


Serum hepatocyte growth factor levels in patients with inflammatory lung diseases.
HGF is a pulmotrophic factor in the regeneration of an injured lung. However, the physiological role of HGF in vivo remains largely unknown. We studied HGF in patients with inflammatory lung diseases to investigate the clinical significance of HGF and compared with C-reactive protein (CRP) in inflammatory lung diseases. Forty-seven patients with inflammatory lung diseases (16 tuberculosis, 18 pneumonia, and 13 chronic obstructive pulmonary disease (COPD)) were studied. Fifty normal, healthy individuals were analyzed as normal control subjects. Serum HGF levels were measured by enzyme-linked immunosorbent assays (ELISA). Serum CRP levels were also performed. The mean +/- SE numbers of serum HGF levels in the patients with inflammatory lung diseases (4.33 +/- 0.41 ng/ml) were significantly elevated when compared with those in normal control subjects (0.36 +/- 0.02 ng/ml) (p < 0.0001). Serum HGF levels in patients with COPD was significantly lower than those were with tuberculosis or pneumonia (p < 0.05). There was a significant correlation between serum HGF levels and CRP in inflammatory pulmonary diseases (r = 0.48, p = 0.00087). The significantly decreased serum HGF levels in patients with improved inflammatory lung diseases were also observed subsequently. Our results suggest that secreted HGF may play an important role in bronchial epithelium reconstruction during respiratory inflammation.


[Effects on electro-scaip acupuncture on cerebral dopamine transporter in patients with Parkinson' s disease].
To investigate the effect of electro-scalp acupuncture (ESA) on dopamine transporter (DAT) in basal ganglia (BG) of patients with Parkinson's disease (PD) by single photon emission computed tomography (SPECT). Ten patients with primary PD were divided equally into two groups randomly. Patients in the treated group received ESA at points of MS6, MS4, MS8, MS9 and MS14, for patients with unilateral lesions, ESA was applied on contralateral points, while for those with bilateral lesions, points of both sides were stimulated, the depth of puncturing was made to arrive at the galea aponeurotica. Patients in the control group took medopa orally in the dosage of 125 mg, 3 times per day for mild, 250 mg, 3 times per day for moderate and 250 mg, 4 times per day for severe cases. All the patients were examined with 99mTc-TRODAT- 1 SPECT before and after 6 weeks' treatment to analyze the activity of DAT by ratio of basal ganglia/occipital (BG/OC) using regional of interesting (ROI) technique. The uptake of 99mTc-TRODAT-1 increased after treatment in both groups. In the treated group, the homolateral (of the affected limbs, the same below) BG/OC ratios before and after treatment were 1.1883 +/- 0.1471 and 1.2416 +/- 0.3146 respectively, and those in the control group 1.1597 +/- 0.0568, 1.2053 +/- 0.1153, showing no significant difference between them (P > 0.05); while the contralateral BG/OC ratios before and after treatment were 0.9019 +/- 0. 1210 and 0.9496 +/- 0.2522 respectively in the treated group, and 1.0436 +/- 0.1393 and 1.2972 +/- 0.2612 respectively in the control group. The difference value of contralateral BG/OC before and after treatment in the control groups was significantly different (P<0.05). But at other cerebral regions, 99mTc-TRODAT-1 SPECT showed no difference between the two groups in changes before and after treatment, therefore, showed no difference in effect of improving DAT between the two groups (P > 0.05). ESA could reduce the loss of DAT in basal ganglia and improve its activity in patients with PD to protect the dopamine neuron, so as to delay the progression of PD and alleviate clinical symptoms of patients.


Bordetella pertussis tracheal cytotoxin.
The most consistent pathological feature of pertussis is the selective colonization and subsequent destruction of ciliated cells in the respiratory epithelium. Phase I B. pertussis can reproduce the human respiratory tract cytopathology during in vitro infection of hamster tracheal organ cultures. However, most isolated biologically active components produced by B. pertussis (lymphocytosis-promoting factor, adenylate cyclase, dermonecrotic toxin, etc.) have no apparent cytopathic effect on the respiratory epithelium. We have purified a glycopeptide from the culture supernatant of virulent B. pertussis that mimics completely the ciliated cell pathology characteristic of pertussis (5). Tracheal cytotoxin (TCT) is released during log phase broth culture and consists of 15 amino acid residues as well as two amino sugars. The selective biological activity of TCT has been studied in tracheal organ cultures by light and electron microscopy. A series of pathological changes precedes the eventual extrusion of ciliated cells, while all other epithelial cell types appear ultrastructurally normal. TCT also causes a dose-dependent inhibition of DNA synthesis in cultured hamster trachea epithelial cells, providing a quantitative bioassay to monitor TCT activity during purification steps. Previously, TCT could be completely purified from oxidized glutathione (a major contaminant from the culture medium) only by high-voltage paper electrophoresis, a procedure not well suited for large scale work. We have now substituted a final column chromatography step that separates TCT from oxidized glutathione and other contaminating peptides. This change and other preparative scale adaptations now allow us to purify 150-250 nmol of biologically active TCT from one liter of culture supernatant (3-4 X 10(13) bacteria), a ten-fold increase over our previous batch size with no increase in processing time.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in household composition as determinant of changes in functional ability among old men and women.
The aims of this article were 1) to describe changes in functional ability from ages 75 to 80 among men and women in three Nordic localities, and 2) to analyze whether these changes are determined by changes in household composition from ages 70 to 75. The present analyses include the persons who participated in the NORA follow-up study of 75-80 year-old men and women in Jyväskylä, Finland (N=243), Göteborg, Sweden (N=226), and Glostrup, Denmark (N=274). Functional ability was measured by tiredness and need for help in Physical and Instrumental Activities of Daily Living (PADL and IADL). Changes in functional ability are described as 1) sustained good, 2) decreased, 3) improved, and 4) sustained poor, and changes in household composition as 1) sustained living alone, 2) from living with others to living alone, and 3) sustained living with others. Number of chronic diseases and home help were included as covariates in the multivariate analyses. A large proportion of men and women had sustained good functional ability from age 75 to 80, but we observed both improvement and deterioration over time. For example, with regard to need for help in PADL: 64/59% of the mer/women had sustained good function, 19/21% deteriorated, 3/6% improved, and 14/14% had sustained poor function. Among the women in need of help at age 75, those who lived alone/became alone had a higher risk of sustained need for help from age 75 to 80 compared to women who lived with others [adjusted OR=4.0 (1.3-12.2/4.4 (0.7-26.9)]. This was not seen among the poor-functioning men. It is concluded that poor-functioning, single-living women are at higher risk of not regaining functional ability compared to cohabiting women.


Alcoholism and psychiatric disorder.
Over the past 50 years the relationship between alcoholism and psychiatric disorders, such as depression, anxiety and schizophrenia, has been the subject of a great deal of research. Psychiatric problems have been seen as both a cause and a result of alcoholism. Whatever the relation between alcoholism and psychiatric disorder is, it may have significance for the development of differentially effective treatment strategies. Several authors have argued that the presence and nature of psychiatric symptoms should form the basis of a classification system for alcoholics. Given the potential rewards of such a system for both understanding the aetiology of alcoholism and developing effective treatment strategies, it is important to have a clear picture of the nature and extent of this relationship. This paper reviews critically the published studies of the association between alcoholism and psychiatric disorder and outlines directions for future research.


[Serum antibodies to hepatitis C virus: analysis of risk factors of seropositivity in a population of blood donors in metropolitan France].
Risk factors were analyzed in a group of 117 blood donors seropositive for hepatitis C virus antibody. One risk factor, at least, was found in 63 (53.8%) subjects. Frequently encountered risk factors were 1) travels in developing countries (31/117); 2) blood transfusions (20/117); 3) health care works (10/117); 4) intravenous drug addiction (8/117); 5) homosexual or multiple heterosexual contacts (3/67). Our study emphasizes the high percutaneous transmission of hepatitis C in contrast with the low sexual transmission. No risk factor could be found in 54 (46.2%) of the 117 seropositive subjects: the route of transmission in these cases is an intriguing issue which certainly deserves further epidemiological investigations.


Nitrate and nitrite content of well water in Enugu, Southeast Nigeria.
Water samples from 20 artesian wells, chosen by the multistage sampling procedure from 5 zones in the city of Enugu, Southeast Nigeria, were analyzed by the disulfonic acid method in duplicate for the presence of nitrate (NO3) and nitrite (NO2). The zonal mean values for NO3 were 0.45 mmol/l, 0.46 mmol/l, 0.55 mmol/l, 0.59 mmol/l, and 0.65 mmol/l (mean = 0.54 mmol/l), and for NO2 the values were 0.34 mmol/l, 0.32 mmol/l, 0.21 mmol/l, 0.14 mmol/l, and 0.20 mmol/l (mean = 0.24 mmol/l), respectively. The mean values were reciprocally related (r = -.7356, p = 0.0002), indicating fecal contamination of well water. There were no significant differences between the mean values and the sum of the NO3 and NO2 values of the samples (p > 0.05), indicating uniform nitrogen content in the region. The mean value for NO3 (0.54 mmol/l) was below the guideline values set by the World Health Organization, but the mean NO2 concentration of 0.24 mmol/l was much higher (290%) than what is considered safe for humans.


Lower Serum Irisin Levels Are Associated with Increased Osteoporosis and Oxidative Stress in Postmenopausal.
Irisin as an exercise-induced myokine was proposed to improve bone health. This study investigated the role of serum irisin (s-irisin) in patients with osteoporosis (OP) through correlating to most biological bone markers and oxidative stress. A cross-sectional study recruited an eligible 175 postmenopausal women at Al-Hussien Teaching Hospital, Iraq. They were scanned by DEXA and stratified into two groups based on T-score; the first 95 patients as control group (GI) with -1 ≤ T-score and the second 80 patients as cases group (GII) with T-score ≤ -2.5. Demographic criteria were age, bone mineral density (BMD, g/cm2) and T-score. Serum irisin, total serum calcium (s-calcium), serum inorganic phosphate (s-phosphate), serum alkaline phosphatase (s-ALP), serum 25 [OH] vitamin D, the serum parathyroid hormone (s-PTH), serum Carboxy terminal collagen crosslinks (CTx), serum procollagen type I C-termidnal peptide (s-PICP), serum malondialdehyde (s-MDA) and serum superoxide dismutase (s-SOD) were collected from blood samples. Serum irisin were 31.84 ± 2.65 vs. 20.88 ± 2.71 ng/mL for control and trial groups, respectively. Lower levels of BMD, T-score, 25 [OH] vitamin D, and s-irisin along with a higher serum levels of PTH, CTx, PICP, MDA and SOD were observed in patients with osteoporosis. All parameters were statistically meaningful upon correlation (p< 0.0001), except age and s-calcium (p= 0.0088 and p= 0.187, respectively). The results showed that, a significantly lower serum irisin levels among osteoporosis women, was intimately correlated to most bone turnover markers and it can be considered as encouraging results for clinical application in prediction and treatment of osteoporosis.


Probing the Pre-diagnostic Phase of Parkinson's Disease in Population-Based Studies.
Parkinson's disease covers a wide spectrum of symptoms, ranging from early non-motor symptoms to the characteristic bradykinesia, tremor and rigidity. Although differences in the symptomatology of Parkinson's disease are increasingly recognized, there is still a lack of insight into the heterogeneity of the pre-diagnostic phase of Parkinson's disease. In this perspective, we highlight three aspects regarding the role of population-based studies in providing new insights into the heterogeneity of pre-diagnostic Parkinson's disease. First we describe several specific advantages of population-based cohort studies, including the design which overcomes some common biases, the broad data collection and the high external validity. Second, we draw a parallel with the field of Alzheimer's disease to provide future directions to uncover the heterogeneity of pre-diagnostic Parkinson's disease. Finally, we anticipate on the emergence of prevention and disease-modification trials and the potential role of population-based studies herein. In the coming years, bridging gaps between study designs will be essential to make vital advances in elucidating the heterogeneity of pre-diagnostic Parkinson's disease.


Puparia Cleaning Techniques for Forensic and Archaeo-Funerary Studies.
Diptera puparia may represent both in forensic and archaeo-funerary contexts the majority of the entomological evidence useful to reconstruct the peri and post-mortem events. Puparia identification is quite difficult due to the lack of identification keys and descriptions. In addition, external substances accumulated during the puparia permanence in the environment make the visualization of the few diagnostic characters difficult, resulting in a wrong identification. Six different techniques based on physical and chemical treatments have been tested for the removal of external substances from puparia to make identification at species level feasible. Furthermore, the effects of these methods on successful molecular analyses have also been tested as molecular identification is becoming an important tool to complement morphological identifications. The results of this study indicate that cleaning via warm water/soap, the sonication and treatment with a sodium hydroxide solution are the best methods to achieve a good quality of the samples.


A Novel Caenorhabditis Elegans Proteinopathy Model Shows Changes in mRNA Translational Frameshifting During Aging.
Regulation of mRNA translation is central to protein homeostasis and is optimized for speed and accuracy. Spontaneous recoding events occur virtually at any codon but at very low frequency and are commonly assumed to increase as the cell ages. Here, we leveraged the polyglutamine(polyQ)-frameshifting model of huntingtin exon 1 with CAG repeat length in the pathological range (Htt51Q), which undergoes enhanced non-programmed translational -1 frameshifting. In body muscle cells of Caenorhabditis elegans, -1 frameshifting occured at the onset of expression of the zero-frame product, correlated with mRNA level of the non-frameshifted expression and formed aggregates correlated with reduced motility in C. elegans. Spontaneous frameshifting was modulated by IFG-1, the homologue of the nutrient-responsive eukaryotic initiation factor 4G (eIF4G), under normal growth conditions and NSUN-5, a conserved ribosomal RNA methyltransferase, under osmotic stress. Our results suggest that frameshifting and aggregation occur at even early stages of development and, because of their intrinsic stability, may persist and accelerate the onset of age-related proteinopathies.


Modulation of antitumor immune responses.
Based on experimentation in animal model systems it is reasonable to expect immunomodulation by anticancer drugs and biological response modifiers to be instrumental in at least some of the antitumor effects of such agents. Even in the defined animal models, however, the immunomodulating effects of any given agent are in most cases correlated only with the therapeutic response to that agent, whereas causal relationships still evade unequivocal demonstration. The difficulties in this respect are magnified in humans, in whom the very nature and regulation of antitumor immunity, taken in a broad sense, are not yet well defined; thus at this time the basis on which to interpret the therapeutic or toxicological causative relevance of an immunomodulating effect is insufficient. Despite these limitations and uncertainties, or perhaps responding to the challenge they provide, experimentation evaluating the potential of immunomodulation is being carried out in a number of diversified areas. Salient findings from selected investigations of the actions of 1) drugs, 2) cytokines, and 3) combinations of agents or effectors are discussed as examples of the realization of the potential of this overall approach as well as to outline the requirements for future development of biological response modifiers.


Global image dissimilarity in macaque inferotemporal cortex predicts human visual search efficiency.
Finding a target in a visual scene can be easy or difficult depending on the nature of the distractors. Research in humans has suggested that search is more difficult the more similar the target and distractors are to each other. However, it has not yielded an objective definition of similarity. We hypothesized that visual search performance depends on similarity as determined by the degree to which two images elicit overlapping patterns of neuronal activity in visual cortex. To test this idea, we recorded from neurons in monkey inferotemporal cortex (IT) and assessed visual search performance in humans using pairs of images formed from the same local features in different global arrangements. The ability of IT neurons to discriminate between two images was strongly predictive of the ability of humans to discriminate between them during visual search, accounting overall for 90% of the variance in human performance. A simple physical measure of global similarity--the degree of overlap between the coarse footprints of a pair of images--largely explains both the neuronal and the behavioral results. To explain the relation between population activity and search behavior, we propose a model in which the efficiency of global oddball search depends on contrast-enhancing lateral interactions in high-order visual cortex.


Complete mitochondrial genome of the serotine bat (Eptesicus serotinus) in Korea.
Serotine bats of Eptesicus serotinus are uncommon species in South Korea due to habit loss and destruction. We describe the characteristics of complete mitochondrial genome and gene organization of E. serotinus in this article. The complete mitogenome of E. serotinus is 16,665 bp long with a total base composition of 32.8% A, 29.8% T, 23.5% C and 13.8% G. The mitogenome consists of 13 protein-coding genes (11,410 bp), 2 rRNA (12S and 16S RNA) genes (2524 bp), 22 tRNA genes (1504 bp) and 1 control region (1225 bp). The results will contribute to understand the genetic structure of Korean E. serotinus.


Missouri's Fentanyl Problem: The China Connection.
Recently, Missouri has followed an overall upward trend in opioid overdose deaths. In 2018, Missouri was the state with the largest absolute and percentage increase in opioid-related overdose fatality rates per capita over the previous year (18.3% and 3.1/100,000). This increase occurred despite an overall decrease in U.S. opioid-related death rates in the same period. This report identifies illicitly manufactured fentanyl (IMF) (and analogues) as the drug most responsible for this rise in opioid deaths in Missouri, with stimulant overdoses (primarily from methamphetamine) in second place. Within Missouri, we find the areas where opioid deaths are highest: St. Louis and the city's fringe areas, following the national trend for high rates in fringe areas. Based on reports from CDC Wonder data, county medical examiners, law enforcement agencies, and drug addiction prevention agencies, we conclude that IMF and related synthetic opioids arriving from China are primarily responsible for fatal narcotic overdoses in Missouri. Despite the COVID-19 disruption of fentanyl manufacturing and distribution centers in and around Wuhan, China early in the pandemic, preliminary 2020 data from medical examiners' offices show an upswing in opioid deaths, an indicator that Chinese fentanyl producers have restored the supply chain.


EWS is a substrate of type I protein arginine methyltransferase, PRMT8.
EWS, a pro-oncoprotein which is encoded by the Ewing sarcoma (EWS) gene, contains arginine-glycine-glycine repeats (RGG box) in its COOH-terminus. We previously found that the RGG box of EWS is a target for dimethylation catalyzed by protein arginine methyltransferases (PRMTs). Although it has been observed that arginine residues in EWS are dimethylated in vivo, the endogenous enzyme(s) responsible for this reaction have not been identified to date. In the present study, we determined that EWS was physically associated with PRMT8, the novel eighth member of the PRMT family, through the COOH-terminal region of EWS including RGG3 with the NH2-terminal region of PRMT8 encompassing the S-adenosyl-L-methionine binding domain, and that arginine residues in EWS were asymmetrically dimethylated by PRMT8 using amino acid analysis with thin-layer chromatography. These results suggested that EWS is a substrate for PRMT8, as efficient as for PRMT1.


Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients.
Fludarabine (FLUDA) based chemotherapy has shown promise in both initial and salvage treatment of low-grade non Hodgkin's lymphomas (LG-NHL). Recently, more aggressive therapies followed by autologous hemopoietic progenitor cell rescue, have also been successfully employed in these patients. However, this procedure, due to several factors including previous therapeutic regimens, is often limited by an inadequate collection of peripheral blood stem cell (PBSC). At present, very little data is available on the effect of FLUDA containing regimens in PBSC collection. We report our preliminary experience showing a possible correlation between FLUDA based chemotherapy regimens employed before mobilization and inability to collect an adequate number of blood derived hematopoietic progenitors for autologous PBSC transplantation in LG-NHL patients.


Use of Nitrogen-15-Enriched Escherichia coli as a Bacterial Tracer in Karst Aquifers.
Karst aquifers are susceptible to contamination by microorganisms, but relatively few studies have used bacteria as tracers. We demonstrate the utility of Escherichia coli enriched in the stable isotope nitrogen-15 (15 N) as a novel bacterial tracer. Nonpathogenic E. coli from two springs in central Kentucky were grown on 15 N-enriched media. Survival of E. coli and persistence of the isotopic signal were assessed in two sets of laboratory experiments conducted with sterilized spring water in dark microcosms at 14 °C. First, isotopically labeled bacteria survived for 130 d at concentrations within one log unit of the average initial value, and there was no significant difference in δ15 N values from Day 1 to Day 130. Second, water samples with E. coli were inoculated with either of two different species of protozoa (Tetrahymena pyriformis or Colpoda steinii). During 7 d, δ15 N values increased in T. pyriformis while bacterial populations decreased. In a field test, following a 2.1-cm rainfall, 15 N-labeled E. coli, solutes (rhodamine WT dye and bromide), and latex microspheres were injected into a sinkhole approximately 530 m upgradient of a spring. Breakthrough of all tracers coincided, but microspheres were remobilized by subsequent storms, unlike other tracers. Enriched E. coli exhibited more tailing than solute tracers during the initial storm-flow recession. These results indicate that 15 N-enriched E. coli is a viable tracer of bacterial transport in karst aquifers, although predation may attenuate the isotopic signal in systems that are not rapidly flushed.


Detection and Distribution of V1016Ikdr Mutation in the Voltage-Gated Sodium Channel Gene in Aedes aegypti (Diptera: Culicidae) Populations From Sergipe State, Northeast Brazil.
Aedes aegypti (L.) resistance to pyrethroids was recorded in Brazil few years after its introduction as the adulticide in the National Dengue Control Program campaigns. Altered susceptibility to pyrethroids had been reported in the state of Sergipe, northeast Brazil, through biological assays, even before its use against Ae. aegypti in the state. Metabolic and target-site resistance mechanisms were also revealed in samples from Aracaju, the capital of Sergipe. Herein, we investigated the presence and distribution of the kdr mutation V1016Ikdr in Ae. aegypti populations from different municipalities of the state. Aedes aegypti eggs were collected from seven municipalities located in areas showing different climatic types and infestation levels. Approximately 20 Ae. aegypti females from each municipality (total of 135 subjects) were individually submitted to allele-specific polymerase chain reaction (AS-PCR) for the 1016 site of the voltage-gated sodium channel (NaV). The V1016Ikdr mutation was found in subjects from all the municipalities under study with a high frequency of heterozygotes in several locations. Homozygous recessive subjects (resistant kdr genotype) were found only in one municipality. The results suggest a wide distribution of the V1016Ikdr mutation in the northeast Brazil, which indicates urgent need for monitoring the effectiveness of the pyrethroids currently used for vector control.


The influence of primary caregivers on body size and self-body image of preschool children in Taiwan.
The purpose of this study was to investigate preschool children's body size and image, and analyze the impact of the primary caregiver on a child's body size and awareness in Taiwan. In a cross-sectional survey, 699 preschool children and their primary caregivers participated in this study. Our study used an anonymous self-administered questionnaire, which was divided into parts A and part B. Part A was a questionnaire for the primary caregivers, including their demographic and anthropometric information, and expectation for children's body size. Part B was a two part questionnaire for children, including the children's expectation on their own body size and their consciousness in terms of body size evaluation by parents and teachers. Data was analyzed by chi-square analysis. In our study, the majority of boys and girls have a normal body size (69.0% and 64.6%, respectively). There was a significant positive correlation (p<0.05) between children and primary caregivers' body size, and a negative correlation (p<0.05) between children body size and caregivers' education level. Furthermore, we found that caregiver's satisfaction and evaluation of the children's body size had significantly affected the children's satisfaction towards their body size. Influences by the primary caregiver is an important factor that affects a preschool child's body size and body image in Taiwan. Body size evaluation by caregivers will influence the child's satisfaction level.


Catheter pinch-off syndrome: recognition and management.
Catheter pinch-off syndrome is an uncommon and often unrecognized complication of central venous catheters. The cause, clinical diagnosis, and management of this unique catheter occlusion are reviewed. Nurses can play a key role in the early detection of catheter pinch-off syndrome as well as the prevention of subsequent catheter fracture and embolization.


Cadmium induces changes in sucrose partitioning, invertase activities, and membrane functionality in roots of Rangpur lime (Citrus limonia L. Osbeck).
Cadmium (Cd) uptake effects on sucrose content, invertase activities, and plasma membrane functionality were investigated in Rangpur lime roots ( CITRUS LIMONIA L. Osbeck). Cadmium accumulation was significant in roots but not in shoots and leaves. Cadmium produced significant reduction in roots DW and increment in WC. Leaves and shoots did not show significant differences on both parameters. Sucrose content was higher in control roots than in Cd-exposed ones. Apoplastic sucrose content was much higher in Cd-exposed roots than in control ones. Cd-exposed roots showed a significant decrease in both cell wall-bound and cytoplasmic (neutral) invertase activities; while the vacuolar isoform did not show any change. Alterations in lipid composition and membrane fluidity of Cd-exposed roots were also observed. In Cd-exposed roots phospholipid and glycolipid contents decreased about 50 %, while sterols content was reduced about 22 %. Proton extrusion was inhibited by Cd. Lipid peroxidation and proton extrusion inhibition were also detected by histochemical analysis. This work's findings demonstrate that Cd affects sucrose partitioning and invertase activities in apoplastic and symplastic regions in Rangpur lime roots as well as the plasma membrane functionality and H (+)-ATPase activity.


Density of middle turbinate subepithelial mucous glands in patients with chronic rhinosinusitis.
Histologic changes have not been systematically assessed in chronic rhinosinusitis. Quantitative histochemical studies evaluated the extent of sinus disease and gland density in the middle turbinates. Sinus computed tomography scans of 34 patients with chronic rhinosinusitis were retrospectively graded 0 to IV according to the May classification. Middle turbinates from patients with chronic rhinosinusitis (n = 46) and normal patients (n = 7) were harvested during endoscopic sinus surgery. The areas of Alcian blue-stained glands were assessed in paraffin sections using a computer-assisted microscopy video system. Alcian blue-stained glands occupied 7.94% of normal mucosa. The staining in all grade III rhinosinusitis subjects was increased to 12.94% (P < 0.01). In contrast, grade IV pansinusitis was associated with nasal polyposis (6 of 6) with decreased gland area (3.04%, P < 0.01). When polyp patients were excluded from grade III rhinosinusitis, the Alcian blue-staining area was 17.68% (P < 0.01). Distinct polypoid and glandular histopathologic patterns are present in chronic rhinosinusitis.


[Advances in the research of treatment of angiogenesis inhibitor on pathological scars].
Angiogenesis inhibitors are a class of agents that prevent the angiogenesis by inhibiting the activation, migration, and proliferation of endothelial cells. In recent years, studies have found that there was a close relationship between the occurrence of pathological scars and angiogenesis. The vascular density in pathological scars is significantly higher than that in normal skin and scars. Neovascularization supports the fibroblasts growth and collagen production, which contribute to the development of pathological scars. Therefore, the angiogenesis inhibitor may become a possible agent for prevention and treatment of pathological scars. This review explores the relationship between pathological scars and angiogenesis inhibitor.


Superoxo, peroxo, and hydroperoxo complexes formed from reactions of rhodium porphyrins with dioxygen: thermodynamics and kinetics.
Rhodium(II) porphyrin complexes react with dioxygen to form terminal superoxo and bridged mu-peroxo complexes. Equilibrium constants for dioxygen complex formation with rhodium(II) tetramesitylporphyrin ((TMP)Rh*) and a m-xylyl-tethered dirhodium(II) diporphyrin complex (*Rh(m-xylyl)Rh*) are reported. (TMP)Rh-H reacts with oxygen to form a transient hydroperoxy complex ((TMP)Rh-OOH), which reacts on to form the rhodium(II) complex ((TMP)Rh*) and water. Kinetic studies for reactions of (TMP)Rh-H with O2 suggest a near concerted addition of dioxygen to the (TMP)Rh-H unit. Reactivity studies for mixtures of H2/O2 and CH4/O2 with the dirhodium(II) complex (*Rh(m-xylyl)Rh*) are reported.


Different susceptibility to polycyclic aromatic hydrocarbons (PAH)-induced DNA damage in lung tissue in male and female non-smokers.
The levels of benzo(a)pyrene diol-epoxide (BPDE)-DNA adducts and polycyclic aromatic hydrocarbons (PAH) were analysed in a limited number of samples of autoptic lung tissue obtained from non-professionally exposed male (n= 13) and female (n= 12) non-smokers in an attempt to evaluate the relationship between gender, lung PAH levels (n= 25) and susceptibility to BPDE-DNA adduct formation (n= 18). Lung concentrations of chrysene, benzo(g,h,i)perylene and benzo(a)pyrene were significantly higher in males than in females (P.


[Concurrent chemoradiotherapy with low-dose weekly docetaxel followed by consolidation chemotherapy with docetaxel and cisplatin in the treatment of stage III non-small cell lung cancer.].
Concurrent chemoradiotherapy is regarded as the standard care for locally advanced non-small cell lung cancer at present. This paper is designed to evaluate the efficacy and toxicity of low-dose weekly docetaxel (DTX) with concurrent chemoradiotherapy followed by consolidation chemotherapy with DTX and cisplatin for unresectable stage III non-small cell lung cancer(NSCLC). 44 previously untreated patients with stage III NSCLC were randomized into low-dose weekly DTX group and control group concomitant with radiotherapy. Both groups were treated by the standard fractionation schedule with three-dimensional conformal radiotherapy. An involved-field irradiation technique was performed. Gross tumor and metastatic lymph nodes were irradiated to a total dose of 66 Gy-70 Gy. Patients in the former group received chemotherapy with DTX 20 mg.m(-2).w(-1), and the other group patients received DTX 60 mg/m(2) on day 1 and DDP 30 mg/m(2) on day 1-3 every 21 days. All patients received consolidation chemotherapy with DP regime after chemoradiotherapy for no more than 4 cycles. The overall response rates of patients in the low-dose weekly DTX group and control group were 81.8% with 27.3% CR(complete response) and 86.4% with 27.3% CR respectively (Chi-Square=0.120, P=0.942). After a median follow-up of 20 months, the median survival time was 20 months and 17 months respectively. The 1-, 2- year survival rates of patients in low-dose weekly DTX group and control group were 69.8%, 48.1% versus 66.5%, 40.2% respectively;there was no difference between two groups. Grade 3 or 4 neutropenia and esophagitis occurred in 26.3%, 14.3% and 15.8%, 28.6% respectively (Chi-Square=0.765, P=0.382;Chi-Square=1.108, P=0.292).Grade 3 and 4 pulmonary toxicity was unusual. Concurrent chemoradiotherapy with low-dose weekly docetaxel followed by consolidation chemotherapy with docetaxel and cisplatin is highly active with manageable toxicity in patients with stage III NSCLC.


Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity.
The phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domain of the proto-oncoprotein p52SHC binds to an NPXpY consensus sequence found in several growth factor receptors (Kavanaugh, W. M., Turck, C. W., and Williams, L. T. (1994) Science 268, 1177-1179). The amino-terminal region of p52SHC, which includes the PTB/PI domain, has been previously shown to associate with protein-tyrosine phosphatase-PEST (PTP-PEST) in vivo (Habib, T. , Herrera, R., and Decker, S. J. (1994) J. Biol. Chem. 269, 25243-25246). We report here the detailed mapping of this interaction in a murine context using glutathione S-transferase fusion protein binding studies and peptide competition assays. We show that the interaction between murine SHC and murine PTP-PEST is mediated through the PTB/PI domain of murine SHC and an NPLH sequence found in the carboxyl terminus of murine PTP-PEST. Since this interaction is not dependent on the presence of a tyrosine-phosphorylated residue in the target sequence, this reveals that the PTB/PI domain of SHC can recognize both tyrosine-phosphorylated sequences and non-tyrosine-based recognition motifs.


Water diffusion in the rabbit lens in vivo.
To examine water diffusion in the crystalline lens and sugar cataracts in the rabbits in vivo. Water self-diffusion in the lens cortices of alloxan-diabetic and galactosemic rabbits was examined with magnetic resonance imaging (MRI). The animals were positioned in a 4.7-tesla animal system in conjunction with a 1-inch surface coil for the eye. Diffusion-weighted MRI was conducted using a pulsed-gradient spin-echo sequence with a gradient strength of 0-6 Gs/cm in the primary and secondary coordinates. Other MRI parameters included TR (repetition time)/TE (echo time) = 2,000/10 ms, a field of view of 4 cm, and a 256 x 128 matrix. There appeared an increase in water relaxation resulting in an increase of % (equatorial cortex depth)/(lens long axis) from 18 in the lenses of normal rabbits to 30.4 and 39.9 in the lenses of galactosemic and diabetic rabbits, respectively. In addition, water diffusion changed in the lens of the diabetic rabbit with an increasing intracellular fluidity along the long axis of the cortical fibers, for example, the diffusion coefficient changed from a normal of 0.48 to 0.96 x 10(-5) cm2 s-1 in the lens of the diabetic rabbit. These results showed altered water mobility due to subcellular disturbances occurring before any apparent lens opacities. Further, there also was an increase in the water diffusivity in the aqueous humor from a normal of 1.77 to 2.67 x 10(-5) cm2 s-1 in the galactosemic rabbit eye suggesting an increase in either free water proportion or thermal convection. Resistance to water self-diffusion appeared to relate to lens fiber orientation and intracellular protein order. Diffusion imaging therefore can be used to examine water self-diffusion to detect early osmotic alteration of lens fibers.


Prognosis Factors of Young Patients Undergoing Curative Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma: A Multicenter Study.
The prognosis of young and older patients with hepatocellular carcinoma (HCC) is controversial. We aim to compare the clinicopathological features and prognosis of young (age ≤40 years) versus older patients (aged >40 years) with hepatitis B virus (HBV)-related HCC after curative resection. A total of 4504 patients with HBV-related HCC who underwent curative resection were included in this study and divided into young group (n=699) and older group (n=3805). Subgroup analyses were conducted to compare. Independent risk factors were identified by Cox regression analysis. Young patients had better ALBI grade, lower rates of liver cirrhosis, higher rates of elevated serum AFP levels, larger tumor size, higher rates of microvascular invasion and macrovascular invasion, higher rates of Edmondson grade III-IV, lower rates of tumor capsular, more advanced AJCC TNM stages and more advanced BCLC stages than older patients (All p<0.05). Meanwhile, young patients had a worse overall survival (OS) rate (p=0.0091) and a worse recurrence-free survival (RFS) rate (p=0.045) than older patients. Multivariate analysis revealed that AFP, resection margin, tumor size, tumor capsular, and macrovascular invasion were associated with OS. The independent risk factors associated with RFS were ALB, tumor size, microvascular invasion, and macrovascular invasion. Young patients had better liver function, more aggressive tumor characteristics, and worse prognosis than older patients. A tumor size of ≥5 cm and macrovascular invasion were associated with poor OS and RFS in young patients. If tumors could be detected at the early stage by more frequent surveillance, long-term survival can be expected in the young patients.


[Background on recent trends in mortality in the Netherlands].
In the Netherlands, a considerable reduction in the annual number of deaths occurred in 2004. This reduction was largely caused by a decrease in the number of deaths from cardiovascular disease. - The risk of dying from cardiovascular disease has decreased in an almost linear manner during the past few decades. This reduction, which was well above average in the case of ischaemic heart disease, was registered for both sexes and across all age groups. The risk reduction in men aged 30-59 years was particularly large. - The contribution of neoplasms to total mortality continues to increase. However, the risk of dying from certain forms of cancer (lung for men, colon for women, stomach, gall-bladder, breast, prostate, uterus and ovaries) has been decreasing since the 1990s. - The risk of dying from breast cancer has decreased since the end of the 1990s. If present trends continue, Dutch women will be more likely to die from lung cancer than breast cancer from 2007 onwards. - The remarkably low mortality in 2004 may be attributed to the equable climatic conditions and the absence of an influenza epidemic. The drop in mortality was short-lived: in the first quarter of 2005, influenza caused a very strong increase in mortality among those aged over 80 years. - Even a further substantial reduction in mortality risks will not be able to prevent the predicted increase in the annual number of deaths in the Netherlands. This increase is estimated to end by the middle of this century.


Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination.
COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination. A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates. We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare. COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.


Spatial Patterns of Anthrax Outbreaks and Cases among Livestock in Lesotho, 2005-2016.
Although anthrax occurs globally, the burden of the disease remains particularly high in Africa. Furthermore, the disease anthrax has significant public health and economic implications. However, sufficient attention has not been given to the geographic distribution of anthrax outbreaks and cases in Lesotho. Therefore, this study investigates the spatial patterns of anthrax outbreaks and cases among livestock in Lesotho from 2005 to 2016. A cross-sectional study design was adopted to realise the objectives of this study using retrospective data of anthrax outbreaks and cases recorded by the Department of Livestock Services (DLS) between 2005 and 2016. Anthrax outbreaks were geo-coded at village level and aggregated at district level. Proportions and 95% CI of anthrax outbreaks and cases by village and district were calculated. Cartographic maps displaying the distribution of anthrax outbreaks and cases at village and district level were constructed. A total of 38 outbreaks were reported over the study period, and they were clustered in the Lowlands districts of Lesotho. Most outbreaks (52.6%, 20/38) in livestock were reported in the Maseru district. The Leribe district reported the lowest proportions of outbreaks (5.3%, 2/38) and cases (0.6%, 3/526). At the village level, 18% (7/38) of outbreaks were in Maseru Urban, followed by Ratau (16%, 6/38) and Mofoka (13%, 5/38). The Maseru district reported the highest (1.3%, 369/29,070) proportion of cases followed by Mafeteng (0.9%, 73/8530). The village with the most cases was Kolo (10.5%, 21/200), followed by Thaba-Chitja (7.7%, 33/430). Anthrax outbreaks and cases exclusively occur in the Lowlands districts of Lesotho, with villages such as Mahobong, Pitseng, Kolo, and Thaba-Chitja having a higher risk of anthrax disease. Findings of the present study have serious public health implications in light of the fact that between 2003 and 2008 Lesotho's main abattoir was closed; hence, most of the meat in Lesotho was imported and/or sourced from the informal slaughter facilities. Much larger studies are needed to further investigate factors contributing to spatial disparities in anthrax outbreaks and cases observed in this study. Findings of the present study can be used to guide the formulation of a policy on prevention and control of anthrax in Lesotho.


[Succesive metastasis in the right orbit with starting point a skin malignant melanoma located under the right clavicle].
It's presented a case of the successive metastases in the right orbit with starting point a malignant melanoma skin located under the right clavicle. It's discussed the raruty situation of the malignant melanomas skin metastases in the orbit.


[Insulin resistance and nitric oxide: molecular mechanisms and pathophysiological associations].
Subclinical inflammation that primarily arises in adipose tissue as a result of its excessive infiltration by immunocompetent cells represents one of the typical etiopathogenetic mechanisms underlying the development of insulin resistance and type 2 diabetes. Immunocompetent cells together with adipocytes are a major source of proinflammatory cytokines triggering proinflammatory cascades that in turn interfere with postreceptor insulin signalling cascade. Recent studies have suggested that inducible nitric oxide synthase plays a key role in this process. Obesity is associated with increased inducible nitric oxide synthase mRNA expression, with subsequent overproduction of nitric oxide and reactive nitrogen species leading to S-nitrosylation of proteins involved in insulin signalling cascade. These post-translational modifications decrease their activity and eventually lead to insulin resistance. Number of experimental studies demonstrated that inhibition of inducible nitric oxide synthase attenuates insulin resistance. The aim of this review is to summarize the current knowledge about the physiology and patophysiology of nitric oxide and inducible nitric oxide synthase with respect to its relationship to insulin resistance and to discuss the possibility of improvement of insulin resistance and type 2 diabetes mellitus by modulating inducible nitric oxide synthase activity.


Core concepts in pharmacoepidemiology: Validation of health outcomes of interest within real-world healthcare databases.
Real-world healthcare data, including administrative and electronic medical record databases, provide a rich source of data for the conduct of pharmacoepidemiologic studies but carry the potential for misclassification of health outcomes of interest (HOIs). Validation studies are important ways to quantify the degree of error associated with case-identifying algorithms for HOIs and are crucial for interpreting study findings within real-world data. This review provides a rationale, framework, and step-by-step approach to validating case-identifying algorithms for HOIs within healthcare databases. Key steps in validating a case-identifying algorithm within a healthcare database include: (1) selecting the appropriate health outcome; (2) determining the reference standard against which to validate the algorithm; (3) developing the algorithm using diagnosis codes, diagnostic tests or their results, procedures, drug therapies, patient-reported symptoms or diagnoses, or some combinations of these parameters; (4) selection of patients and sample sizes for validation; (5) collecting data to confirm the HOI; (6) confirming the HOI; and (7) assessing the algorithm's performance. Additional strategies for algorithm refinement and methods to correct for bias due to misclassification of outcomes are discussed. The review concludes by discussing factors affecting the transportability of case-identifying algorithms and the need for ongoing validation as data elements within healthcare databases, such as diagnosis codes, change over time or new variables, such as patient-generated health data, are included in these data sources.


Double-layer broadband antireflection coatings for grazing incidence angles.
This paper presents the methodology for the design of double-layer antireflection (AR) coatings forgrazing incidence angles for a given state of polarization. The designs are based on commonly used thin-film materials with the optical constants that can be realized by using standard evaporation techniques. The performance of some AR stacks has been computed, and the effect on spectral reflectance with variation in the thickness of the high-index layer, angle of incidence, and the refractive indices of the materials used for the inner and outer layers has been studied with a view to selecting a suitable design that gives the lowest reflectance over the widest wavelength range. The AR stacks show a reflectance of <0.5% over most parts of the visible and near-infrared regions of the spectrum.


Interactions between carboxylic acids and aldehydes: a rotational study of HCOOH-CH2O.
The rotational spectrum of the 1:1 complex between formic acid and formaldehyde shows that the two units are linked together through a "classical" (OH···O) and a weak (CH···O) hydrogen bond. The molecular system appears quite rigid, and no effects of the internal motions have been observed in the spectrum.


Some considerations of radiation-induced cell transformation in vitro.
Experimental data concerning the influence of the cell density on the induction rate of cell transformations in C3H mouse embryo cell lines (1OT1/2) after X-irradiation have been reanalysed. The mathematical analysis showed that the transformation frequency can be expressed as the product of two functions, one of which is dependent on radiation dose alone, and the other of which is dependent on the number of cell division cycles alone, in that the probability of the expression of malignant transformation is constant per cellular mitosis. Therefore the transformation frequency measured for different experimental conditions can be normalized and consequently compared; one example of data reduction after irradiation by alpha-particles is demonstrated.


Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain.
This study investigated whether metabotropic glutamate receptor (mGluR) 5 and 8 are involved in the effect of ultramicronizedpalmitoylethanolamide (um-PEA) on the cognitive behavior and long term potentiation (LTP) at entorhinal cortex (LEC)-dentate gyrus (DG) pathway in mice rendered neuropathic by the spare nerve injury (SNI). SNI reduced discriminative memory and LTP. Um-PEA treatment started after the development of neuropathic pain had no effects in sham mice, whereas it restored cognitive behavior and LTP in SNI mice. 2-Methyl-6-(phenylethynyl) pyridine (MPEP), a selective mGluR5 antagonist, improved cognition in SNI mice and produced a chemical long term depression of the field excitatory postsynaptic potentials (fEPSPs) in sham and SNI mice. After theta burst stimulation (TBS) MPEP restored LTP in SNI mice. In combination with PEA, MPEP antagonized the PEA effect on discriminative memory and decreased LTP in SNI mice. The (RS)-4-(1-amino-1-carboxyethyl)phthalic acid (MDCPG), a selective mGluR8 antagonist, did not affect discriminative memory, but it induced a chemical LTP and prevented the enhancement of fEPSPs after TBS in SNI mice which were treated or not treated with PEA. The effect of PEA on LTP and cognitive behavior was modulated by mGluR5 and mGluR8. In particular in the SNI conditions, the mGluR5 blockade facilitated memory and LTP, but prevented the beneficial effects of PEA on discriminative memory while the mGluR8 blockade, which was ineffective in itself, prevented the favorable action of the PEA on LTP. Thus, although their opposite roles (excitatory/inhibitory of the two receptor subtypes on the glutamatergic system), they appeared to be required for the neuroprotective effect of PEA in conditions of neuropathic pain.


Direct proline-catalyzed asymmetric alpha-aminoxylation of aldehydes and ketones.
The direct proline-catalyzed asymmetric alpha-aminoxylation of aldehydes and ketones has been developed using nitrosobenzene as an oxygen source, affording alpha-anilinoxy-aldehydes and -ketones with excellent enantioselectivity. Reaction conditions have been optimized, and low temperature (-20 degrees C) was found to be a key for the successful alpha-aminoxylation of aldehydes, while slow addition of nitrosobenzene is essential for that of ketones. The scope of the reaction is presented.


Evaluation of the productivity decrease risk due to a future increase in tropical cyclone intensity in Japan.
A number of scientists have recently conducted research that shows that tropical cyclone intensity is likely to increase in the future. This would result in an increase in the damage along with a decrease in economic productivity due to precautionary cessation of the economic activity of the affected areas during the passage of the cyclone. The economic effect of this stop in economic activity is a phenomenon that has not received much attention in the past, and the cumulative effect that it can have on the Japanese economy over the next 75 years has never been evaluated. The starting point for the evaluation of the economic risks is the change in the patterns of tropical cyclone intensity suggested by Knutson and Tuleya. The results obtained show how a significant decrease in the overall productivity of the country could be expected, which could lower GDP by between 6% and 13% by 2085.


Payments for ecosystem services as a framework for community-based conservation in northern Tanzania.
Payments for ecosystem services (PES) are an increasingly promoted approach to conservation. These approaches seek to develop financial mechanisms that create economic incentives for the maintenance of ecosystems and associated biodiversity by rewarding those who are responsible for provision of ecological services. There are, however, few cases in which such schemes have been used as a strategy for conserving wildlife in developing countries and very few operational examples of such schemes of any sort in sub-Saharan Africa. In savannah ecosystems, large mammal populations generally depend on seasonal use of extensive areas and are widely declining as a result of habitat loss, overexploitation, and policies that limit local benefits from wildlife. Community-based conservation strategies seek to create local incentives for conserving wildlife, but often have limited impact as a result of persistent institutional barriers that limit local rights and economic benefits. In northern Tanzania, a consortium of tourism operators is attempting to address these challenges through an agreement with a village that possesses part of a key wildlife dispersal area outside Tarangire National Park. The operators pay the community to enforce voluntary restrictions on agricultural cultivation and permanent settlement in a defined area of land. The initiative represents a potentially cost-effective framework for community-based conservation in an ecologically important area and is helping to reconcile historically conflicting local and national interests relative to land tenure, pastoralist livelihoods, and conservation. Wider adaptation of payments for ecosystem services approaches to settings where sustaining wildlife populations depends on local stewardship may help address current challenges facing conservation outside state-protected areas in savannah ecosystems in sub-Saharan Africa and other parts of the world.


Effect of calcium ion concentration on the permeability of the corneal endothelium.
The effect of free Ca2+ ion concentration on the integrity of the barrier function of the corneal endothelium was studied using the endothelial permeability to carboxyfluorescein (Pac) as a quantitative index according to the method of Araie. Paired rabbit corneas were isolated and mounted in a chamber. To serve as a control, one eye of each pair was perfused with a glucose-glutathione-bicarbonate solution at a Ca2+ concentration of 1.1 mEq, the other with a solution at various Ca2+ concentrations ranging from 0.23-1.1 mEq. The Pac ratio of a solution with a Ca2+ concentration of 0.38 mEq or higher to the control solution was close to unity, and the Pac ratio of a solution with a Ca2+ concentration of 0.33 mEq or lower to the control solution was significantly greater than unity. In a separate experiment, it was found that only slight swelling was seen when a solution with a Ca2+ concentration of 0.23 mEq or higher was used; significant swelling was seen with a solution of a Ca2+ concentration of 0.17 mEq or lower. The lowest free Ca2+ concentration needed for maintaining the barrier function of the corneal endothelium, 0.38 mEq, was found to be higher than that needed for maintaining the corneal thickness, 0.23 mEq.


31P magnetic resonance spectroscopy of animal uveal melanoma.
Scleral surface coils were used to obtain in vivo magnetic resonance spectra (MRS) of Greene melanoma implanted in the rabbit uvea. Well-localized tumor spectra (4.7 Tesla) with good signal-to-noise ratios (S/N) were obtained from the tumor with a "single-pulse" sequence in less than 1 hour. Tumor localization was confirmed with one-dimensional spectroscopic imaging studies. Serial 31P spectra were obtained during tumor growth and after both optimal and suboptimal hyperthermia. Early 31P MRS change is correlated with tumor treatment response and preceded histologic evidence of cell destruction. Twenty-four to 48 hours after successful treatment, the inorganic phosphate/nucleoside triphosphate (NTP), and phosphomonoester/NTP ratios were significantly increased from 1.2 +/- 0.1 to 1.7 +/- 0.1 and 1.3 +/- 0.1 to 1.8 +/- 0.2, respectively. In contrast, untreated or ineffectively treated tumors showed little change. Interpretation of 31P MRS data in this animal uveal melanoma model after the first week was complicated by decreased S/N, increased contamination from contiguous tissues, ingrowth of fibroblasts, macrophages, and intratumor hemorrhage.


Comparison of the cyclic fatigue resistance of VDW.ROTATE, TruNatomy, 2Shape, and HyFlex CM nickel-titanium rotary files at body temperature.
This study aims to compare the cyclic fatigue resistance of VDW.ROTATE, TruNatomy, 2Shape, and HyFlex CM nickel-titanium (NiTi) rotary files at body temperature. In total, 80 VDW.ROTATE (25/0.04), TruNatomy (26/0.04), 2Shape (25/0.04), and HyFlex CM (25/0.04) NiTi rotary files (n = 20 in each group) were subjected to static cyclic fatigue testing at body temperature (37°C) in stainless-steel artificial canals prepared according to the size and taper of the instruments until fracture occurred. The number of cycles to fracture (NCF) was calculated, and the lengths of the fractured fragments were measured. The data were statistically analyzed using a 1-way analysis of variance and post hoc Tamhane tests at the 5% significance level (p < 0.05). There were significant differences in the cyclic fatigue resistance among the groups (p < 0.05), with the highest to lowest NCF values of the files as follows: VDW.ROTATE, HyFlex CM, 2Shape, and TruNatomy. There was no significant difference in the lengths of the fractured fragments among the groups. The scanning electron microscope images of the files revealed typical characteristics of fracture due to cyclic fatigue. The VDW.ROTATE files had the highest cyclic fatigue resistance, and the TruNatomy and 2Shape files had the lowest cyclic fatigue resistance in artificial canals at body temperature.


Genetic Diversity within Snap Beans and Their Relation to Dry Beans.
Two hundred forty-six snap bean genotypes and 49 dry beans representing both centers of domestication and six bean races with materials from Europe, Asia, and the Americas were genotyped using a single nucleotide polymorphism (SNP) array. The data was analyzed for expected heterozygosity, K-means clustering, principal components, phylogenetic relationships, and population substructure. When all gene pools of snap bean were assembled, the expected heterozygosity was roughly equivalent to a carefully chosen panel of dry beans representing all bean races and centers of domestication demonstrating the genetic richness of snap materials in total. K-means clustering and K = 2 structure analysis showed significant mixing of gene pools in the European and American commercial snap materials and the dominance of the Andean center of domestication among commercial contemporary snap beans. Conversely, the same analysis showed that Chinese, Iberian, and heirloom materials were underrepresented in contemporary materials. Further, Structure analysis revealed eight distinct groups within snap beans. Two showed strong kinship to the Middle American center of domestication, three to the Andean center of domestication, and three showed admixture between the two centers. Snap beans may have been independently derived from dry beans more than once and from both centers. Overall, we identified eight potential germplasm pools for snap bean.


[A toddler with complicated otorrhea].
A 4-year-old boy was diagnosed with intracranial abscess following adequately treated otorrhea and mastoiditis. This is an uncommon finding. He underwent mastoidectomy with drainage of the abscess. In cases where patients clinically deteriorate during treatment for otorrhea and mastoiditis, further examination using CT-scan is recommended.


Nonsurgical Adjuncts Following Facelift to Achieve Optimal Aesthetic Outcomes: "Icing on the Cake".
This article discusses the various nonsurgical treatments that can be performed in combination with facelift surgery to provide patients with a more complete facial rejuvenation. Nonsurgical adjuncts focus on facial volume enhancement, skin resurfacing, intense pulsed light for pigmentary changes, neuromodulators, and skin care in addition to the surgical techniques used to combat facial aging. Several options exist for skin resurfacing, including dermabrasion, chemical peels, and lasers; the advantages and limitations of each are discussed. Photographs demonstrating the effectiveness of nonsurgical treatments to facelift patients are displayed as examples of their powerful adjunctive effect.


Limited ability of DNA polymerase kappa to suppress benzo[a]pyrene-induced genotoxicity in vivo.
DNA polymerase kappa (Polk) is a specialized DNA polymerase involved in translesion DNA synthesis. To understand the protective roles against genotoxins in vivo, we established inactivated Polk knock-in gpt delta (inactivated Polk KI) mice that possessed reporter genes for mutations and expressed inactive Polk. In this study, we examined genotoxicity of benzo[a]pyrene (BP) to determine whether Polk actually suppressed BP-induced genotoxicity as predicted by biochemistry and in vitro cell culture studies. Seven-week-old inactivated Polk KI and wild-type (WT) mice were treated with BP at doses of 5, 15, or 50 mg/(kg·day) for three consecutive days by intragastric gavage, and mutations in the colon and micronucleus formation in the peripheral blood were examined. Surprisingly, no differences were observed in the frequencies of mutations and micronucleus formation at 5 or 50 mg/kg doses. Inactivated Polk KI mice exhibited approximately two times higher gpt mutant frequency than did WT mice only at the 15 mg/kg dose. The frequency of micronucleus formation was slightly higher in inactivated Polk KI than in WT mice at the same dose, but it was statistically insignificant. The results suggest that Polk has a limited ability to suppress BP-induced genotoxicity in the colon and bone marrow and also that the roles of specialized DNA polymerases in mutagenesis and carcinogenesis should be examined not only by in vitro assays but also by in vivo mouse studies. We also report the spontaneous mutagenesis in inactivated Polk KI mice at young and old ages. Environ. Mol. Mutagen. 58:644-653, 2017. © 2017 Wiley Periodicals, Inc.


Working with an Aboriginal community liaison worker.
FPA Health (Family Planning NSW) has conducted two integrated clinical and health promotion projects with Aboriginal communities in western NSW, Australia. The first was in Coonamble, a small rural community which had been selected as a pilot site for the Royal Australian College of General Practitioners Women's Aboriginal and Torres Strait Islander Project and was managed by FPA Health with support from the Dubbo/Plains Division of General Practice and Macquarie Area Health Service. The second was in Dubbo, a regional city where FPA Health had an existing centre and which had funding support from the Rio Tinto Aboriginal Foundation. The aim of this article was to share the learning and knowledge gained in managing these projects and to describe the experience of working with Aboriginal Community Liaison Workers who belong to and are supported by, the local Aboriginal community. The article aimed to illustrate the role and value of utilising these workers within a mainstream health service. The beneficial outcomes include improving service provision to Aboriginal women, adding to community knowledge about reproductive and sexual health issues and increasing the cultural knowledge and competency of a mainstream health service organisation.


Laboratory exploration of survival of probiotic cultures inside the human digestive tract using in vitro models.
Scientists often model complex biological phenomena in vitro, mimicking conditions found in living organisms. Understanding the power and limitations of biological models is an important topic in undergraduate science. In this activity, students develop their own in vitro model for testing the survival of bacteria from commercial probiotic supplements. Students work in groups to decide which factors are important for survival of bacteria in a chosen portion of the human digestive tract. Groups of students create their own in vitro models of organs such as stomach and/or intestines. Students expose a probiotic supplement to conditions mimicking the chosen portion of the human digestive tract, and measure the effect of those conditions on the survival of bacteria found in the supplement. Students choose to focus on conditions such as low pH found in stomach or pancreatic enzymes found in the upper intestine. Through this activity, students gain experience with serial dilutions and calculations of colony forming units (CFUs). This project also provides the students with the valuable experience of designing experiments in small groups. Students present their findings in a poster session, which provides a venue for discussing the validity and limitation of various models.


Lack of dichotomy between virus load of peripheral blood and lymph nodes during long-term simian immunodeficiency virus infection of African green monkeys.
During the asymptomatic phase of human immunodeficiency virus 1 (HIV-1) infection the lymphatic tissues seem to function as a major reservoir of HIV. We have examined the viral load in peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) of 12 naturally and 4 experimentally long-term simian Immunodeficiency virus (SIV)-infected African green monkeys (AGM) to help explain the apathogenicity of the AGM isolates of SIV (SIVagm) in their natural host. The mean number of SIVagm producing cells determined by limiting dilution assay was found to be 1.7 +/- 2.2 and 2.1 +/- 3.3 per 10(5) PBMC or LNMC, respectively. Similarly, polymerase chain reaction analysis of serially diluted cells showed the mean provirus carrying cell number to be 2.8 +/- 3.7 per 10(5) PBMC and 4.0 +/- 5.5 per 10(5) LNMC. When normalized for CD4+ cells the provirus and infectious virus loads in the LNMC and PBMC were also similar. No trapping of virus particles could be detected by in situ hybridization or immunohistochemistry. The data demonstrate that in contrast to HIV-1-infected humans, the viral burden in the lymph nodes of long-term SIV(agm)-infected AGMs is comparable to that in the PBMC.


Glucose variability and mood in adults with diabetes: A systematic review.
To systematically review the literature regarding the association between glucose variability (GV) and mood in adults with diabetes, appraise the used methods and make suggestions for future research. A systematic review of literature published up to May 2019 was performed. Abstracts and full texts were screened independently in duplicate. Experimental and observational studies reporting the association between GV and mood in adults with type 1 diabetes or type 2 diabetes were evaluated. A descriptive analysis of the extracted data was conducted, along with a quality assessment. Out of the 2.316 studies screened, eight studies met our criteria. Studies used a variety of measures and metrics to determine GV and mood. Four studies used continuous glucose monitoring (CGM). An association between GV and mood was found in four studies when correlating either postprandial glucose rate of increase with current mood or multiday GV with mood measured retrospectively. The other four studies did not find any association. There is no clear empirical support for a link between GV and mood in adults with type 1 and type 2 diabetes. More rigorous research is warranted using CGM and ecological momentary assessment of mood to assess if and under what conditions an association between GV and mood exists.


Band-like electron transport in organic transistors and implication of the molecular structure for performance optimization.
The Hall effect and an increase of field-effect mobility with decreasing temperature is observerd in n-channel single-crystal organic field-effect transistors (OFETs). A quantitative analysis of these findings, together with results on different p-channel transistors, indicate the importance of the semiconductor molecular polarizability and the structure of the charge transport layers in the crystal for the observation of band-like transport in OFETs.


Voltage clamp experiments in striated muscle fibres.
1. Membrane currents during step depolarizations were determined by a method in which three electrodes were inserted near the end of a fibre in the frog's sartorius muscle. The theoretical basis and limitations of the method are discussed.2. Measurements of the membrane capacity (C(M)) and resting resistance (R(M)) derived from the current during a step change in membrane potential are consistent with values found by other methods.3. In fibres made mechanically inactive with hypertonic solutions (Ringer solution plus 350 mM sucrose) step depolarizations produced ionic currents which resembled those of nerve in showing (a) an early transient inward current, abolished by tetrodotoxin, which reversed when the depolarization was carried beyond an internal potential of about +20 mV, (b) a delayed outward current, with a linear instantaneous current-voltage relation, and a mean equilibrium potential with a normal potassium concentration (2.5 mM) of -85 mV.4. The reversal potential for the early current appears to be consistent with the sodium equilibrium potential expected in hypertonic solutions.5. The variation of the equilibrium potential for the delayed current (V'(K)) with external potassium concentration suggests that the channel for delayed current has a ratio of potassium to sodium permeability of 30:1; this is less than the resting membrane where the ratio appears to be 100:1. V'(K) corresponds well with the membrane potential at the beginning of the negative after-potential observed under similar conditions.6. The variation of V'(K) with the amount of current which has passed through the delayed channel suggests that potassium ions accumulate in a space of between (1/3) and (1/6) of the fibre volume. If potassium accumulates in the transverse tubular system (T system) much greater variation in V'(K) would be expected.7. The delayed current is not maintained but is inactivated like the early current. The inactivation is approximately exponential with a time constant of 0.5 to 1 sec at 20 degrees C. The steady-state inactivation of the potassium current is similar to that for the sodium current, but its voltage dependence is less steep and the potential for half inactivation is 20 mV rate more positive.8. Reconstructions of ionic currents were made in terms of the parameters (m, n, h) of the Hodgkin-Huxley model for the squid axon, using constants which showed a similar dependence on voltage.9. Propagated action potentials and conduction velocities were computed for various conditions on the assumption that the T system behaves as if it were a series resistance and capacity in parallel with surface capacity and the channels for sodium, potassium and leak current. There was reasonable agreement with observed values, the main difference being that the calculated velocities and rates of rise were somewhat less than those observed experimentally.


Metachronous gastrointestinal stromal tumor and acute leukemia after liver transplantation for cholangiocellular carcinoma: is there a link?
The synchronous or metachronous coexistence of gastrointestinal stromal tumors (GISTs) with solid and hematologic neoplasms has been addressed in a non-transplant population. However, the association with primary hepatic neoplasms and leukemias is uncommon. Scarce data exist considering association of GISTs and other neoplasms in a transplant population where long-term immunosuppression carries the additional burden of de novo malignancy. We present a case of posttransplant metachronous GIST and acute biphenotypic leukemia in a patient transplanted for intrahepatic cholangiocellular carcinoma, emphasizing the possible link between mechanisms of carcinogenesis and influence of other factors upon their development.


Snoezelen: benefits for nursing older clients.
In this article, the authors examine the possible benefits of Snoezelen for older clients. The authors suggest that nurses can be instrumental in developing and creating innovative therapeutic environments for this vulnerable client group.


Immune-related pancreatitis associated with checkpoint blockade in melanoma.
Recognizing and treating rare checkpoint inhibitor related adverse events may be a clinical challenge in melanoma therapy. One of rather rare affected organs is the pancreas. Immune-related pancreatitis is difficult to recognize due to its variable clinical characteristics. Asymptomatic elevations of serum lipase and/or amylase during therapy with immune-checkpoint blockade impede the diagnostic process. We present a patient who developed an immune-related pancreatitis within the first 4 months of immunotherapy. Treatment with high dose systemic glucocorticosteroids with very slow tapering over a total period of 6.5 months was necessary to keep the patient symptom free as well as to maintain long-term normalization of serum lipase. Checkpoint blockade related pancreatitis may occur as acute or chronic disease and may lack any radiographic signs. As in our case, very slow tapering of initially high dose systemic glucocorticosteroids seems to be a crucial requirement for lasting recovery. Even after successful treatment, late-onset secondary pancreatic insufficiency may occur and patients have to be followed up at regular intervals. Restarting immunotherapy after resolution of immune-related pancreatitis is possible but needs careful risk-benefit consideration.