Low Ca2+ stripping of differentiating cell layers in human epidermal cultures: an in vitro model of epidermal regeneration.
An in vitro model of the epidermal regeneration process is described. Incubation of multilayered, keratinizing cultures of human epidermal cells in Ca2+-free medium for 72 h results in a complete stripping of all suprabasal layers. When the Ca2+ stripped cultures are refed normal Ca2+ medium a reproducible series of morphologic and cell kinetic changes takes place. It is suggested that these changes represent a general pattern of regeneration after epidermal wounding. After an initial lag phase the regenerative response is principally effected by a recruitment to the proliferating pool of cells with a high rate of DNA synthesis. The cells seem to be programmed to rapid differentiation. Studies with cholera toxin suggest that this adenylate cyclase-stimulating agent is able to induce significant changes in the regenerative process causing a prolonged, but less intense, proliferative response leading to lateral growth rather than to rapid differentiation.


Speckle Tracking of the Basal Lateral and Septal Wall Annular Plane Systolic Excursion of the Right and Left Ventricles of the Fetal Heart.
Annular plane systolic excursion (APSE) has been evaluated for the right (RV) and left (LV) ventricles using M-mode echocardiography. This study examined APSE using 2-dimensional speckle tracking (2DST) of the lateral and septal annuli of the RV and LV in normal fetuses. Two hundred normal fetuses were prospectively examined between 20 and 40 weeks' gestation, in which the end-diastolic and end-systolic lengths were measured from the apex to the insertion of the annuli into the lateral and septal walls of the RV and LV using 2DST. Subtracting the end-systolic from the end-diastolic length resulted in the APSE measurement. The APSE values from the ventricular and septal locations were regressed against biometric and gestational age independent variables, and the mean and standard deviation computed using fractional polynomial analysis. Within-subject repeated measures of variance were used to compare results within and between the right ventricular and left ventricular basal APSE values. When regressed against the independent variables the R2 for the APSE of the right ventricular lateral wall ranged from 0.39 to 0.40, the left ventricular lateral wall 0.29 to 0.31, the right ventricular septal wall 0.22 to 0.40, and the left ventricular septal wall 0.05 to 0.07. There was a significant difference (P < .001) for APSE between the right ventricular and left ventricular lateral wall and their respective septal annuli, the left ventricular and right ventricular lateral wall annuli, and the left ventricular and right ventricular septal annuli. The right ventricular and left ventricular lateral and septal wall APSE can be computed using 2DST and are associated with changing fetal biometric and age measurements.


Thermal emission spectra of the Earth and atmosphere from the Nimbus 4 Michelson interferometer experiment.
Profiles of atmospheric temperature, humidity and ozone can be recovered from the thermal emission spectra in the interval 400 to 1,500 cm(-1) obtained from the Nimbus 4 satellite. The spectra can also be used to study surface restrahlen effects and other geophysical and meteorological phenomena.


Reperfusion-induced arrhythmias are not prevented by ibuprofen in isolated rat heart.
Free radicals have been implicated in the genesis of reperfusion-induced arrhythmias and the cyclooxygenase pathway has been suggested as a potential source. We have therefore assessed whether a cyclooxygenase inhibitor, ibuprofen, is able to reduce reperfusion-induced injury in the isolated perfused rat heart. A duration of 10 min of regional ischemia, which resulted in a high (83%) incidence of ventricular fibrillation, was selected and hearts (n = 12/group) were perfused with ibuprofen (2, 20, or 30 mg/L) throughout the experiment. Ibuprofen did not affect heart rate, although it did produce a dose-dependent increase in coronary flow. However, at all doses studied, ibuprofen had no effect upon the time to onset, incidence, or duration of arrhythmias. In subsequent studies with 30 min of regional ischemia, ibuprofen (30 mg/L) again caused vasodilatation but without effect upon heart rate or severity of arrhythmias. In conclusion, we were unable to obtain evidence in support of the concept that cyclooxygenase activity or cyclooxygenase-derived free radicals are involved in the genesis of ischemia- and reperfusion-induced arrhythmias.


Association between prenatal exposure to ambient particulate matter and risk of hypospadias in offspring: A systematic review and meta-analysis.
Epidemiological studies on whether prenatal exposure to PM2.5, PM2.5-10, and PM10 increases the risk of hypospadias are limited and the results are inconsistent. We conducted this systematic review and meta-analysis to evaluate these associations. Relevant studies were identified by searching the PubMed and Embase databases up to the end of February 2020. Observational studies that investigated the relationships between prenatal exposure to PM10, PM2.5, and PM2.5-10 and the risk of hypospadias in offspring were eligible for the review. The risk of bias was evaluated using the Newcastle-Ottawa scale. Random-effects models were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the associations. Nine studies (two cohort and seven case-control studies) with a total of 2806 hypospadias cases were included. Eight studies were at low risk of bias and only one study was at high risk of bias. Five studies reported the association between per interquartile range increase in PM2.5 exposure within the first trimester and the risk of hypospadias. The pooled RR was 1.17 (95% CI: 1.00, 1.36). Two studies reported the per interquartile range increase in PM2.5 exposure during 1 month before pregnancy associated with the risk of hypospadias, with a pooled RR of 1.25 (95% CI: 1.03, 1.51). No association was observed between PM2.5-10 and PM10 exposure during pregnancy and the risk of hypospadias in offspring. This study suggested a modest association between prenatal PM2.5 exposure during 1 month before pregnancy or within the first trimester and the risk of hypospadias in offspring. Further large-scale cohort studies are required to verify this association.


Unveiling the migration of Cr and Cd to biochar from pyrolysis of manure and sludge using machine learning.
Heavy metal (HM) in biochar derived from pyrolysis of sludge or manure is the main issue for its large-scale application in soils for carbon sequestration. However, there is a paucity of efficient approaches to predict and comprehend the HM migration during pyrolysis for preparing low HM-contained biochar. Herein, the data on the feedstock information (FI), additive, total concentration of feedstock (FTC) of HM (i.e., Cr and Cd), and pyrolysis condition, were extracted from the literature, to predict total concentration (TC) and retention rate (RR) of Cr and Cd in sludge/manure biochar using machine learning for mapping their migration during pyrolysis. Two datasets for Cr and Cd were compiled with 388 and 292 data points from 48 and 37 peer-review papers. The results indicated that the TC and RR of Cr and Cd could be predicted by the Random Forest model with test R2 of 0.74-0.98. Their TC and RR in biochar were dominated by the FTC and FI, respectively; while pyrolysis temperature was the most important to Cd RR. Moreover, potassium-based inorganic additives decreased the TC and RR of Cr while increased those of Cd. The predictive models and insights provided by this work could aid the understanding of HM migration during manure and sludge pyrolysis and guide the preparation of low HM-contained biochar.


Activity of Ceftolozane-Tazobactam Against Gram-Negative Isolates from Australia and New Zealand as part of the PACTS Surveillance 2016-2018.
Ceftolozane-tazobactam (C-T) is an anti-pseudomonal cephalosporin combined with a well-described β-lactamase inhibitor. Ceftolozane-tazobactam has enhanced activity against Pseudomonas aeruginosa, and activity against Enterobacterales isolates that produce extended-spectrum β-lactamases (ESBLs) or AmpC cephalosporinases. In this study, we analysed the susceptibility of Gram-negative isolates to C-T and comparators collected in Australia and New Zealand from 2016 to 2018 as part of the Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) surveillance. A total of 1693 nonduplicate Enterobacterales and 435 P. aeruginosa isolates were collected prospectively from hospitalized patients in six medical centres in Australia and two in New Zealand. Susceptibilities (S) to C-T and comparators were determined using broth microdilution. EUCAST breakpoints were used. Isolates with multi-drug resistant (MDR), extensively drug resistant (XDR), extended-spectrum β-lactamase non-carbapenem resistant (ESBL, non-CRE) phenotype, and CRE were analysed. For P. aeruginosa, 97.5% were S to C-T while 89.9% were S to meropenem. According to EUCAST criteria, 86.4% were susceptible-increased exposure to piperacillin-tazobactam. MDR and XDR P. aeruginosa isolates had 76.7% and 65.4% S to C-T, respectively; 34.9% and 19.2% S to meropenem, respectively; and 23.3% and 15.4% were susceptible-increased exposure to piperacillin-tazobactam, respectively. Meropenem (99.8% S), amikacin (99.1% S), and C-T (96.5% S) were the most active against Enterobacterales. Susceptibilities to C-T were 94.3% for ESBL, non-CRE phenotype, and 78.4% for MDR isolates. Only three CRE and five XDR isolates were identified. These in vitro data indicate that C-T is a potent antimicrobial with activity against MDR and XDR P. aeruginosa, as well as ESBL, non-CRE phenotype isolates and MDR Enterobacterales.


Tumor reversion and embryo morphogenetic factors.
Several studies have shown that cancer cells can be "phenotypically reversed", thus achieving a "tumor reversion", by losing malignant hallmarks as migrating and invasive capabilities. These findings suggest that genome activity can switch to assume a different functional configuration, i.e. a different Gene Regulatory Network pattern. Indeed, once "destabilized", cancer cells enter into a critical transition phase that can be adequately "oriented" by yet unidentified morphogenetic factors - acting on both cells and their microenvironment - that trigger an orchestrated array of structural and epigenetic changes. Such process can bypass genetic abnormalities, through rerouting cells toward a benign phenotype. Oocytes and embryonic tissues, obtained by animals and humans, display such "reprogramming" capability, as a number of yet scarcely identified embryo-derived factors can revert the malignant phenotype of several types of tumors. Mechanisms involved in the reversion process include the modification of cell-microenvironment cross talk (mostly through cytoskeleton reshaping), chromatin opening, demethylation, and epigenetic changes, modulation of biochemical pathways, comprising TCTP-p53, PI3K-AKT, FGF, Wnt, and TGF-β-dependent cascades. Results herein discussed promise to open new perspectives not only in the comprehension of cancer biology but also toward different therapeutic options, as suggested by a few preliminary clinical studies.


Fatigue-resistance of the internal rotator muscles in the tennis player's shoulder: isokinetic and electromyographic analysis.
The main objective is to determine whether there are differences in the relative isokinetic and electromyographic responses between the internal rotator (IR) muscles on the dominant and non-dominant sides of tennis players during performance of an isokinetic fatigue protocol. Ten male tennis players were recruited for this isokinetic and electromyographic study. Participants performed 35 concentric maximal voluntary actions, carrying out internal rotations of both shoulders at an angular velocity of 120° s(-1). Maximal torque (T((45°))Max), torque decrease (T((45°))), Root Mean Square normalised (RMSnorm) and Neuromuscular Efficiency (NME) parameters were analysed. Although an increased T((45°))Max was observed on the dominant side compared to the non-dominant side, the progression of torque differences did not indicate differences in fatigue-resistance between the two sides. RMSnorm was also higher on the dominant side compared to the non-dominant side, without showing a fatigue effect. NME values decreased during performance of the fatigue protocol without any side effect. Practicing tennis induces an increased T((45°))Max on the dominant side compared to the non-dominant side, but does not appear to provoke differences in the fatigue-resistance of IR muscles. EMG analysis showed that the fatigue induced was mainly peripheral (from metabolic and ionic changes).


Association between health insurance membership and anaemia among children under-five years. Evidence from Ghana.
Anaemia is prevalent among children in developing countries. The main objective of this study was to assess the association between health insurance membership and anaemia among Ghanaian children under-five years. We obtained Ghana's Multiple Indicators Cluster Survey, 2011 dataset from the United Nations International Children's Emergency Fund. Data were analyzed with the aid of Stata/IC, version 15. The prevalence of anaemia among Ghanaian children under-five years was estimated to be 57%. Majority (73%) of the children were not insured. Health insurance membership was found to be a significant predictor of anaemia among children under-five years. Health insurance membership is a protective factor against anaemia among children under-five years. In the quest to eradicate anaemia among children, stakeholders would have to review the benefit package of the National Health Insurance Scheme coupled with prioritizing anaemia prevention interventions among more vulnerable children.


Development of infrared optical sensor for selective detection of tyrosine in biological fluids.
In this paper, a new and simple evanescent wave type of infrared biosensor is described for the selective detection of tyrosine in biological fluids. This sensor is based on the formation of copper complexes between the sensing phase and tyrosine. To demonstrate that this principle was applicable to the selective detection of tyrosine, a proline-modified sensing phase was synthesized on the surface of the internal reflection elements. This sensing phase was saturated with copper ions to allow it to interact with tyrosine units in aqueous solution through the formation of stable proline-Cu2+-tyrosine complexes. Tyrosine exhibits a unique spectral feature in its absorption band at 1515 cm-1. This band significantly differs from those of other amino acids and provides a further method for the discrimination of tyrosine. By investigating the signals from 12 amino acids, only three amino acids, each containing a phenyl group, could be sensed selectively by this sensing phase. Based on the unique absorption of tyrosine located at 1515 cm-1, tyrosine can be selectively detected. To perform quantitative analyses of tyrosine using this sensing phase, a theoretical working equation was developed and correlated with the experimental data. The analytical results indicated that the developed equations do explain and predict the detection behaviors of the proposed sensing scheme. Using the optimal conditions, the regression coefficients for standard curves of tyrosine recorded in the region of concentrations below 600 microM were higher than 0.996 under either equilibrium or non-equilibrium conditions. Detection limit of tyrosine when using this method was ca. 3 microM.


The activation of natural killer cell effector functions by cetuximab-coated, epidermal growth factor receptor positive tumor cells is enhanced by cytokines.
Natural killer (NK) cells express an activating Fc receptor (FcgammaRIIIa) that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab is a therapeutic monoclonal antibody directed against the HER1 antigen. We hypothesized that the NK cell response to cetuximab-coated tumor cells could be enhanced by the administration of NK cell-stimulatory cytokines. Human NK cells stimulated with cetuximab-coated tumor cells and interleukin-2 (IL-2), IL-12, or IL-21 were assessed for ADCC and secretion of IFN-gamma and T cell-recruiting chemokines. IL-21 and cetuximab were given to nude mice bearing HER1-positive xenografts. Stimulation of human NK cells with cetuximab-coated tumor cells and IL-2, IL-12, or IL-21 resulted in 3-fold to 10-fold higher IFN-gamma production than was observed with either agent alone. NK cell-derived IFN-gamma significantly enhanced monocyte ADCC against cetuximab-coated tumor cells. Costimulated NK cells also secreted elevated levels of chemokines (IL-8, macrophage inflammatory protein-1alpha, and RANTES) that could direct the migration of naive and activated T cells. IL-2, IL-12, and IL-21 enhanced NK cell ADCC against tumor cells treated with cetuximab. The combination of cetuximab, trastuzumab (an anti-HER2 monoclonal antibody), and IL-21 mediated greater NK cell cytokine secretion and ADCC than any agent alone. Furthermore, administration of IL-21 enhanced the effects of cetuximab in a murine tumor model. These results show that cetuximab-mediated NK cell activity can be significantly enhanced in the presence of NK cell-stimulatory cytokines. These factors, therefore, may be effective adjuvants to administer, in combination with cetuximab, to patients with HER1-positive malignancies.


Maternal history of childhood maltreatment is associated with diurnal cortisol and DNA methylation of placental 11-beta-hydroxysteroid dehydrogenase type 2.
Accumulating evidence indicates that maternal hypothalamic-pituitary-adrenal (HPA) axis activity over pregnancy differs according to maternal history of childhood maltreatment. DNA methylation of the placental 11-beta-hydroxysteroid dehydrogenase (BHSD) type 2 enzyme regulates fetal exposure to maternal cortisol, yet the association between maternal history of childhood maltreatment and methylation of placental 11BHSD type 2 has not been previously studied. We examined if maternal cortisol production at 11 and 32 weeks' gestation (n = 89) and placental methylation of the 11BHSD type 2 gene (n = 19) differed among pregnant women with and without histories of childhood maltreatment. Twenty-nine percent of participants reported a history of childhood maltreatment (physical/sexual abuse). Women with histories of childhood maltreatment displayed lower cortisol in early gestation, hypo-methylation of placental 11BHSD type 2, and lower levels of cord blood cortisol. Preliminary results suggest alterations in cortisol regulation over pregnancy according to maternal history of childhood maltreatment.


Acute phorbol ester treatment inhibits thapsigargin-induced cell death in porcine aortic smooth muscle cells.
We have previously shown that, in porcine aortic smooth muscle cells, endoplasmic reticulum (ER) stressor thapsigargin simultaneously activate the mitochondrial caspase-dependent death cascade and an extracellular signal-regulated kinase (ERK)-dependent pathway, which inhibits the caspase-independent death pathway. Our aim in the present study was to examine the effect of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on these processes. We found that thapsigargin induced autophagy, which led to cell death. Treatment of cells with PMA for 5min, which activates protein kinase C (PKC), partially inhibited thapsigargin-induced cell death, whereas PMA treatment for 24h, which downregulates PKC, did not. This protection after short PMA treatment was not due to inhibition of the thapsigargin-induced cytosolic calcium concentration increase, mitochondrial permeability transition pore (PTP) opening, or caspase-3 activation, but coincided with increased ERK phosphorylation and decreased autophagosome formation and the decreased autophagosome formation was prevented by the ERK kinase inhibitor PD98059. Thus, under conditions of ER stress caused by thapsigargin-induced disturbance of calcium homeostasis, PKC activation induced ERK phosphorylation, which inhibited autophagic, but not apoptotic, cell death. After acute PMA treatment, protection against thapsigargin-induced cell death was enhanced by the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone or the PTP blocker cyclosporin A, but decreased by PD98059 or the PKC inhibitor Go6983. Taken together, these results suggest that PKC activation alleviates ER stress and that this is attributable to enhanced ERK phosphorylation, which inhibits autophagic, but not apoptotic, cell death.


Application of Choices criteria in Brazil: impact on nutrient intake and adequacy of food products in relation to compounds associated to the risk of non-transmissible chronic diseases.
One of the aims of this work was to evaluate the impact of introducing products that are in agreement with the Choices criteria in the usual diet of the Brazilian population. However, due to the insufficient information on key compounds related to non-transmissible chronic diseases (NTCD) in the national food composition database, the nutritional information of food labels was collected. A food composition database of industrialized products was created (1720 products) and their data were evaluated according to the Choices criteria. The replacement of typical products by products that are in accordance to the Choices criteria may cause a decrease in the intake of saturated (52%) and trans fatty acids (92%), energy (14%) and sodium (47%), as well as an increase in the intake of DF (87%); improving the diet nutritional profile. This procedure can be used as important part in a strategy for decreasing the risk for NTCD.


[Study on the expression of human acute myeloid leukemia retrovirus gene].
To explore the potentiality of retroviral etiology in human acute myeloid leukemia (AML). The expression of retrovirus clone 6 # 11 in leukemic cells from 19 AML patients and peripheral blood mononuclear cells (PBMNCs) from 20 controls was studied by Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR). Northern blot revealed the positive bands of 9.4 kb and 4.5 kb in 18 of 19 AML patients, and RT-PCR a 790 bp product in 11 of 14 AML patients. There was a specific expression of acute myeloid leukemia associated retrovirus in AML patients.


A reversible method for sound analysis adapted to bio-acoustical experiments.
The paper describes a method of sound analysis, 'modulation analysis', its implementation on a minicomputer PDP12 and some aspects of its application in bioacoustical experiments. Modulation analysis reversibly resolves a given sound signal into time-courses of amplitude and carrier frequency. Since time is preserved as the independent variable the method provides a suitable basis for the computer modification of sounds. Problems of practical performance are discussed with regard to sounds of birds and insects. Further, the use of sound modification in a neurophysiological study of the hearing system of birds is described.


Relationship between knee osteoarthritis and the locomotive syndrome risk tests: A cross-sectional study.
To determine the relationship between locomotive syndrome (LS) risk tests and knee osteoarthritis (KOA). Cross-sectional cohort study. In 2015, 225 people (male 84, females 141, mean age 67.9, range 30-90) were examined using LS risk tests, including the stand-up test, the two-step test, and the 25-question risk assessment, in Katashina Village in Gunma prefecture. The Japanese orthopaedic association defined LS risk test stage 1, difficulty with standing from a 40-cm-high seat using one-leg in the stand-up test, two-step test <1.3, the 25-question risk assessment ≧7, and defined stage 2, difficulty with standing from a 20-cm-high seat using both legs in the stand-up test, two-step test <1.1, the 25-question risk assessment ≧16. Persons with two or more of the following on the ultrasound (US) assessment were defined as having KOA: peripheral joint space (PJS) < 5 mm during weight-bearing; medial radial displacement (MRD) > 5 mm during weight-bearing; and osteophytes > 2 mm. If the residents had KOA in either knee, they were defined as having KOA. 45 residents had KOA in either knee. Logistic regression analysis adjusted for age, height, weight, gender, and knee pain was performed with stage 0 as reference. On the stand-up test, the odds ratio was 5.484 (95% confidence interval (CI) 1.966-15.297) for stage 1 and 2.067 (95% CI 0.426-10.017) for stage 2. On the two-step test, the odds ratio was 1.497 (95% CI 0.557-4.021) for stage 1 and 0.71 (95% CI 0.210-2.395) for stage 2. On the 25-question risk assessment, the odds ratio was 1.73 (95% CI 0.646-4.631) for stage 1 and 1.5 (95% CI 0.508-4.433) for stage 2. A stand-up test of stage 1 had a significant relationship with KOA. This might suggest that proper care of KOA is needed to prevent progressive disability.


Structure of apoproteins in insect lipophorin.
The two polypeptide chains of cockroach and locust lipophorins were separated and their amino acid compositions were determined. Circular dichroic spectra of the lipophorins and apolipophorin from 190 to 250 nm showed a single trough at 218 nm and a peak at 194 nm. Infrared spectra of the lipophorins in D2O showed a strong peak at 1625 cm-1 and a weak shoulder at 1693 cm-1 corresponding to v (pi, 0) and nu (0, pi) of antiparallel pleated sheet. The resonance frequency splitting delta nu = nu (0, pi) -nu (pi, 0) was 68 cm-1, which was larger than that of ordinary globular proteins containing antiparallel pleated sheet. From circular dichroic and infrared spectra it was concluded that lipophorins contained polypeptides rich in antiparallel pleated sheet with longer unbroken extensions than the case for ordinary globular proteins. Partial proteolytic digestion study of lipophorins with trypsin, chymotrypsin, and subtilisin showed that the larger apolipophorin (AL1) was exposed to the surface of the particle and the smaller apolipophorin (AL2) lay protected from the attack of the enzymes. Crosslinked products between AL1 and AL2 were readily obtained when dimethylsuberimidate or dimethyladipimidate was added to the lipophorin solution, without giving lipophorin dimers, suggesting that the two chains were located within 11 A from each other. Such structural features of insect lipoprotein were compared with other insect lipophorins and the human serum low-density lipoprotein (LDL). Similarities between lipophorins and LDL were found in the molecular weight, amino acid compositions, and the secondary structure of major apoproteins.


Complete restoration of auditory impairment in a pediatric case of Cogan's syndrome: report of a rare case with long-term follow-up and literature review.
Cogan's syndrome is characterized by interstitial keratitis, vestibular impairment and hearing loss, commonly bilateral. Many patients, especially children, experience a delay in proper diagnosis which may delay treatment and thus impact on prognosis of hearing restoration. Less than 10 pediatric cases of Cogan's syndrome have been reported in literature and only five of them were reported with long-term follow-up. We report an extremely rare pediatric case of Cogan's syndrome typical form with long-term follow-up and evaluation of hearing impairment. Cogan's syndrome must be familiar to otorhinolaryngologists, pediatricians and ophthalmologists because early diagnosis and rapid administration of the proper therapy increase the probability of recovering hearing loss.


Germline predictors of androgen deprivation therapy response in advanced prostate cancer.
To evaluate whether germline variations in genes involved in sex steroid biosynthesis and metabolic pathways predict time to treatment failure for patients with advanced prostate cancer undergoing androgen deprivation therapy (ADT), because there are few known clinical predictors of response. In a cohort of 304 patients with advanced prostate cancer undergoing ADT, we genotyped 746 single-nucleotide polymorphisms (SNPs) from 72 genes from germline DNA (680 tagSNPs from 58 genes and 66 candidate SNPs from 20 genes [6 genes common in both]). Association with the primary end point of time to ADT failure was assessed using proportional hazards regression models at the gene level (for genes with tagging SNPs) and at the SNP level. False discovery rates (FDRs) of 0.10 or less were considered noteworthy to account for multiple testing. At the gene level, TRMT11 showed the strongest association with time to ADT failure (P<.001; FDR=0.008). Two of 4 TRMT11 tagSNPs were associated with time to ADT failure. Median time to ADT failure for rs1268121 (A>G) was 3.05 years for the AA, 4.27 years for the AG, and 6.22 years for the GG genotypes (P=.002), and for rs6900796 (G>A), it was 2.42 years for the GG, 3.52 years for the AG, and 4.18 years for the AA genotypes (P<.001). No other gene level or SNP level tests had an FDR of 0.10 or less. Genetic variation in TRMT11 was associated with time to ADT failure. Confirmation of these preliminary findings in an independent cohort is needed.


A trial of povidone-iodine ointment for the prevention of cannula thrombophlebitis.
The efficacy of povidone-iodine ointment in the prevention of cannula thrombophlebitis was assessed in a prospective controlled study of 100 consecutive patients. Thrombophlebitis was evaluated clinically, and in addition all cannulae were cultured, semi-quantitatively and by the conventional broth technique, to detect any bacterial colonization. The incidence of thrombophlebitis was slightly higher in the test than in the control group. It is concluded that the use of povidone-iodine ointment for prophylaxis does not reduce the incidence of cannula thrombophlebitis. There was no significant association between the incidence of thrombophlebitis and cannula colonization as measured by either the semi-quantitative technique or the conventional broth technique.


Thermal denaturation and fluorescence study of nucleosomes containing non-histone chromosomal protein HMG2.
Interaction of calf thymus non-histone chromosomal protein HMG2 with H1,H5-depleted nucleosomes from chicken erythrocytes was studied by means of thermal denaturation and an N-(3-pyrene)maleimide fluorescence probe. Under low ionic conditions (2 mM Tris buffer plus EDTA) addition of 1-2 molecules of HMG2 per nucleosome markedly stabilized the segment of the linker DNA against thermal denaturation. Under approximately physiological ionic conditions (0.1 M NaCl) addition of two HMG2 molecules per nucleosome, labeled by N-(3-pyrene)maleimide at the sulfhydryl groups of Cys-110 of histones H3, resulted in a decrease of the pyrene excimer fluorescence corresponding to the slight movement of the sulfhydryl groups of the two histone H3 molecules apart.


Temporal changes in the microbiome of stingless bee foragers following colony relocation.
Maintaining beneficial interactions with microbial symbionts is vital for animal health. Yet, for social insects, the stability of microbial associations within and between cohorts is largely unknown. We investigated temporal changes in the microbiomes of nine stingless bee (Tetragonula carbonaria) colonies at seven timepoints across a 10-month period when moved between two climatically and florally different sites. Bacterial 16S rRNA gene and fungal ITS amplicon sequencing confirmed that microbiomes varied considerably between colonies initially at site one. However, following relocation, considerable changes occurred in bacterial community composition within each colony, and the microbiome composition became more similar across colonies. Notably, Snodgrassella disappeared and Zymobacter appeared as relatively abundant taxa. Remarkably, bacterial communities within colonies continued to shift over time but remained similar across colonies, becoming dominated by Acinetobacter six months after returning to the original site. Our results indicate that the stingless bee microbiome can undergo major changes in response to the environment, and that these changes can be long-lasting. Such legacy effects have not been reported for corbiculate bees. Further understanding the microbial ecology of stingless bees will aid future management of colonies used in agricultural production.


Cortico-cortical connections of the limbic cortex of the rat.
By means of the retrograde transport of fluorescent tracers (Fast Blue, True Blue, Fluorogold and Diamidino Yellow), the cortico-cortical connections of prelimbic, insular, anterior and posterior cingulate (retrosplenial) areas have been studied. Our results demonstrate that there are, in the cortex of the adult rat, a few cells which have branched axons with connections in the ipsilateral hemisphere (associational neurons) or in the contralateral hemisphere (callosal neurons). The callosal neurons could be separated into two categories: "double callosal" neurons which project both axon collaterals to two cortical areas of the contralateral hemisphere, and "associational-callosal" neurons which send axon collaterals to both hemispheres.


Total Marrow and Lymphoid Irradiation with Post-Transplantation Cyclophosphamide for Patients with AML in Remission.
Graft-versus-host disease (GVHD) has remained the main cause of post-transplantation mortality and morbidity after allogeneic hematopoietic cell transplantation (alloHCT), adding significant economic burden and affecting quality of life. It would be desirable to reduce the rate of GVHD among patients in complete remission (CR) without increasing the risk of relapse. In this study, we have tested a novel conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000 cGy, together with post-transplantation cyclophosphamide (PTCy) for patients with acute myeloid leukemia in first or second CR, to attenuate the risk of chronic GVHD by using PTCy, while using escalated targeted radiation conditioning before allografting to offset the possible increased risk of relapse. The primary objective was to evaluate the safety/feasibility of combining a TMLI transplantation conditioning regimen with a PTCy-based GVHD prophylaxis strategy, through the assessment of adverse events in terms of type, frequency, severity, attribution, time course, duration, and complications, including acute GVHD, infection, and delayed neutrophil/platelet engraftment. Secondary objectives included estimation of non-relapse mortality (NRM), overall survival (OS), relapse-free survival, acute and chronic GVHD, and GVHD-relapse-free survival (GRFS). A patient safety lead-in was first conducted to ensure there were no unexpected toxicities and was expanded on the basis of lack of dose-limiting toxicities. The patient safety lead-in segment followed 3 + 3 dose expansion/(de-)escalation rules based on observed toxicity through day 30; the starting dose of TMLI was 2000 cGy, and a de-escalation to 1800 cGy was considered. After the safety lead-in segment, an expansion cohort of up to 12 additional patients was to be studied. TMLI was administered on days -4 to 0, delivered in 200 cGy fractions twice daily. The radiation dose delivered to the liver and brain was kept at 1200 cGy. Cyclophosphamide was given on days 3 and 4 after alloHCT, 50 mg/kg each day for GVHD prevention; tacrolimus was given until day 90 and then tapered. Among 18 patients with a median age of 40 years (range 19-56), the highest grade toxicities were grade 2 Bearman bladder toxicity and stomatitis. No grade 3 or 4 Bearman toxicities or toxicity-related deaths were observed. The cumulative incidence of acute GVHD grade 2 to 4 and moderate-to-severe chronic GVHD were 11.1% and 11.9%, respectively. At a median follow up of 24.5 months, two-year estimates of OS and relapse-free survival were 86.7% and 83.3%, respectively. Disease relapse at 2 years was 16.7%. The estimates of NRM at 2 years was 0%. The GVHD/GRFS rate at 2 years was 59.3% (95% confidence interval, 28.8-80.3). This chemotherapy-free conditioning regimen, together with PTCy and tacrolimus, is safe, with no NRM. Preliminary results suggest an improved GRFS rate.


Same-Day Versus Next-Day Discharge Strategies for Left Atrial Ablation Procedures: A Parallel, Intra-Institutional Comparison of Safety and Feasibility.
Head-to-head comparative data for the postoperative care of patients undergoing left atrial ablation procedures are lacking. We sought to investigate complication and readmission rates between patients undergoing same-day (SD) or next-day (ND) discharges for ablative procedures in the left atrium, primarily atrial fibrillation (AF). Two electrophysiology centers simultaneously perform left atrial ablations with differing discharge strategies. We identified all patients who underwent left atrial ablation from August 2017 to August 2019 (n = 409) undergoing either SD (n = 210) or ND (n = 199) discharge protocols. We analyzed any clinical events that resulted in procedural abortion, extended hospitalization, or readmission within 72 hours. The primary endpoint of complication and readmission rate was similar between SD and ND discharge (14.3% vs 12.6%, p = 0.665). Rates of complications categorized as major (2.4% vs 3.0%, p = 0. 776) and minor (11.9% vs 9.5%, p = 0.524) were also similar.Multivariable regression modeling revealed no significant correlation between discharge strategy and complication/readmission occurrence (OR 1.565 [0.754 - 3.248], p = 0.23), but a positive association of hypertension and procedure duration (OR 3.428 [1.436 - 8.184], p = 0.006) and (OR 1.01 [1 - 1.019], p = 0.046) respectively. Left atrial ablation complication and readmission rates were similar between SD and ND discharge practices. Hypertension and procedural duration were associated with increased complication rates irrespective of discharge strategy. These data, which represent the first side-by-side comparison of discharge strategy, suggests same-day discharge is safe and feasible for left atrial ablation procedures.


Malignant hyperthermia: routine monitoring and early detection.
A case of malignant hyperthermia during an emergency operation is described. The anesthetic management for the same patient undergoing a subsequent operation is also described. The importance of adequate monitoring during anesthesia is discussed.


Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer's disease and cancer.
Alzheimer's disease (AD) and cancer are common age-related diseases, and epidemiological evidence suggests an inverse relationship between them. However, investigating the potential mechanism underlying their relationship remains insufficient. Based on genome-wide association summary statistics for 42,034 AD patients and 609,951 cancer patients from the GWAS Catalog using the two-sample Mendelian randomization (MR) method. Moreover, we utilized two-step MR to identify metabolites mediating between AD and cancer. Furthermore, we employed colocalization analysis to identify genes whose upregulation is a risk factor for AD and demonstrated the genes' upregulation to be a favorable prognostic factor for cancer by analyzing transcriptomic data for 33 TCGA cancer types. Two-sample MR analysis revealed a significant causal influence for increased AD risk on reduced cancer risk. Two-step MR analysis identified very low-density lipoprotein (VLDL) as a key mediator of the negative cause-effect relationship between AD and cancer. Colocalization analysis uncovered PVRIG upregulation to be a risk factor for AD. Transcriptomic analysis showed that PVRIG expression had significant negative correlations with stemness scores, and positive correlations with antitumor immune responses and overall survival in pan-cancer and multiple cancer types. AD may result in lower cancer risk. VLDL is a significant intermediate variable linking AD with cancer. PVRIG abundance is a risk factor for AD but a protective factor for cancer. This study demonstrates a causal influence for AD on cancer and provides potential molecular connections between both diseases.


Differential effects of zinc on hyperpolarizing and depolarizing GABAA synaptic potentials in hippocampal slice cultures.
We have examined the changes in GABAA-mediated synaptic potentials recorded from CA3 pyramidal neurons in hippocampal slice cultures following application of zinc (Zn2+). Unlike 4-AP, Zn2+ did not enhance fast hyperpolarizing potentials but primarily enhanced depolarizing GABAA potentials. Zn2+ did not alter the postsynaptic response of pyramidal neurons to pressure applied GABA, consistent with previous reports that Zn2+ enhances the release of GABA from presynaptic terminals. To examine the role of local circuitry in the production of Zn2+ responses, we recorded from cultures maintained for 7-10 days following removal of the dentate and hilus to allow complete degeneration of the mossy fibers (DGX cultures). Zn2+ produced giant depolarizing potentials (GDPs) in DGX cultures that were identical to those in intact cultures. In contrast, the 4-AP response was dramatically altered in DGX cultures. In DGX cultures, Zn2+ co-applied with 4-AP appeared to inhibit the production of fast hyperpolarizing GABAA synaptic potentials produced by 4-AP alone. This inhibition of fast hyperpolarizing potentials suggests that Zn2+ may reduce the release of GABA onto pyramidal cell somata. These observations suggest that Zn2+ enhances GABA release from local circuit neurons that synapse onto pyramidal cell dendrites, and inhibits GABA release onto pyramidal cell somata.


Conformational change of DNA binding subunit of RNA polymerase II on binding to DNA.
The spatial arrangement of the subunits of RNA polymerase II from Ehrlich ascites tumor cells was investigated by measuring the sensitivity of each subunit in the native enzyme to various proteinases. The results showed that the largest two subunits (a and b) were sensitive to all the proteinases tested, whereas two smaller subunits (e and h) were resistant to these enzymes. These results suggest that in the native enzyme subunits e and h are located in the inside of RNA polymerase II, forming a core. It was also found that the conformation of the DNA binding subunit a changes when the enzyme binds to DNA, and it becomes much more susceptible to chymotryptic digestion.


Quantitative effect of H-2-linked gene(s) on antibody response to human gamma-globulin.
H-2-linked gene(s) have been found to play a role in the quantitative regulation of response to human gamma-globulin (HGG) in mice selected for high or low antibody responsiveness to sheep erythrocytes. Unexpectedly, in a random genetically heterogeneous population of F2 interline hybrids, the gene(s) linked to the H-2 phenotype of H mice has a "low" effect, and the gene(s) linked to the H-2 phenotype of L mice a "high" effect on the magnitude of antibody response to HGG. In H and L mice, the non-specific polygenic control of antibody responsiveness is able to compensate/counteract the inverse effect of HGG-specific H-2-linked gene(s) since the usual interline difference is observed.


A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma.
A phase II study testing the safety and efficacy of irinotecan (CPT-11). 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with advanced gastric adenocarcinomas. Patients with metastatic or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach were entered onto this study. Previous chemotherapy for metastatic disease was not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125 mg/m2 intravenously (i.v.) followed immediately by LCV 20 mg/m2 i.v. and 5-FU 500 mg/m2 i.v., all given weekly for four weeks followed by a two-week rest. Thirty-eight patients were enrolled and 36 eligible patients received protocol therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3 (8%) dying of neutropenic sepsis. The overall response rate was 22% (95% confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and median time to progression was 4.4 months. This weekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and diarrhea were similar to those observed historically in patients receiving this regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more frequent, and dose modifications were substantial. Future trials of this combination in patients with gastric cancer should decrease the absolute starting drug doses and/ or employ altered scheduling that better accommodates the pattern of toxicity.


Acculturation and endocrine disrupting chemical-associated personal care product use among US-based foreign-born Chinese women of reproductive age.
Personal care products (PCPs) are an important source of endocrine disrupting chemicals (EDCs) linked to adverse reproductive health outcomes. We evaluated EDC-associated PCP use and acculturation among Asian women. Our study included 227 foreign-born Chinese women ages 18-45 seeking obstetrics-gynecology care at community health centers (Boston, MA). Acculturation was measured by English-language use, length of US residence, and age at US entry. Self-reported use of PCPs (crème rinse/conditioner, shampoo, perfume/cologne, bar soap/body wash, liquid hand soap, moisturizer/lotion, colored cosmetics, sunscreen, and nail polish) in the last 48 h was collected. Latent class analysis was used to identify usage patterns. We also conducted multivariable logistic to determine the cross-sectional associations of acculturation measures and the use of individual PCP types. Those who used more PCP types, overall and by each type, tended to be more acculturated. Women who could speak English had 2.77 (95% CI: 1.10-7.76) times the odds of being high PCP users compared to their non-English speaking counterparts. English-language use was associated with higher odds of using perfume/cologne and nail polish. Our findings give insight about EDC-associated PCP use based on acculturation status, which can contribute to changes in immigrant health and health disparities.


Assessing the pain experience in children.
A paucity of literature exists on the experience of children in pain: however, its study is most relevant to the pediatric nurse who must care for the child. It is necessary for the nurse to understand the influential factors that affect the perceptions and expressions of children who have pain before she can intervene in a comfort-producing and health-promoting manner.


Melatonin profile in marmots: the influence of catecholamines, hibernation, and light.
The aim of this study was to determine the effects of circulating catecholamines and light on the daily melatonin rhythm in the marmot. Endogenous levels of circulating catecholamines and plasma melatonin were measured during arousal from hibernation in light and studies were performed on the circadian melatonin rhythm in two photoperiods (LD 4:20 and LD 8:16). In addition, studies were done on the capacity of broad-band white light at normal room intensities (32 muW/cm2 or 108 Ix) and of low-intensity monochromatic green light (500 nm; 1.4muW/cm2 or 3.1 Ix) to suppress high nocturnal melatonin levels. We conclude that high levels of plasma catecholamines that occur during arousal from hibernation do not influence the production and secretion of pineal melatonin. During the nocturnal portion of its light/dark cycle, the marmot plasma melatonin rhythm is suppressed by both white light and low-intensity green light.


Microbial responses using denaturing gradient gel electrophoresis to oil and chemical dispersant in enclosed ecosystems.
Microbial responses to the addition of oil with or without a chemical dispersant were examined in mesocosm and microcosm experiments by using denaturing gradient gel electrophoresis of bacterial ribosomal DNA and direct cell counting. When a water-soluble fraction of oil was added to seawater, increases in cell density were observed in the first 24h, followed by a decrease in abundance and a change in bacterial species composition. After addition of an oil-dispersant mixture, increases in cell density and changes in community structure coincided, and the amount of bacteria remained high. These phenomena also occurred in response to addition of only dispersant. Our results suggest that the chemical dispersant may be used as a nutrient source by some bacterial groups and may directly or indirectly prevent the growth of other bacterial groups.


Thin-layer chromatographic in situ analysis of insect ecdysones via fluorescence-quenching.
The possibility of quantitating insect ecdysones in situ on thin-layer chromatographic plates was examined. Two approaches were evaluated: 1) the induction of ecdysone fluorescence by sulfuric acid treatments and 2) the fluorescence-quenching of fluorescent thin-layer chromatographic plates by ecdysones. The fluorescence-quenching method was found to be most suitable and had a linear response range from 0.5 to 3 microgram for alpha-ecdysone and 20-hydroxyecdysone. Fluorescence-quenching and high pressure liquid chromatographic analyses obtained from extracts of alpha-ecdysone 20-hydroxylase incubations gave similar results. New data concerning the acid-induced fluorescence of ecdysones showed alpha-ecdysone to be twice as fluorescent as 20-hydroxyecdysone.


Diabetes Medication Satisfaction Tool: a focus on treatment regimens.
To develop and test a patient questionnaire on treatment satisfaction with diabetes regimens. Survey items were developed from community clinic focus groups, pretested in patients with diabetes, and examined in two samples of treated patients. Sixteen items performed well in assessing treatment experiences: ease and convenience, lifestyle burdens, well-being, and medical control. Construct validity was supported by associations (P < 0.05) with treatment complexity, self-rated glucose control, health worries, and A1C. Internal consistency ranged from 0.89 to 0.95. The Diabetes Medication Satisfaction Tool offers a comprehensive assessment of patient acceptability, with diabetes therapy useful for individualizing therapeutic decision making.


Tailoring a compact and stable Langmuir bi-dimensional PbX-based layered perovskite film at the air-water interface and on solid support.
The present work studies the stability of Langmuir organic-inorganic superlattice materials thin films consisting of layered perovskite-based films with controlled 2D framework as well as to design experimental conditions for increasing the efficiency of the organic-inorganic perovskite motif by mechanical stimulus. Therefore, a whole covering of the air/water interface by a compact and stable lead-based layered perovskite structure is pursued. A 2D layered perovskite-type hybrid structure of the form [(CH3(CH2)19NH3)2(PbX4)], X=Cl, and Br, in which, two-dimensional sheets stabilized by a inner bilayer of organic monoammonium cation matrix, is mechanically tailored by successive compression-expansion cycles. The formation of 2D molecular patterns has been characterized by ΔR, BAM, XRD and XPS.


Changes in amino-acid composition of developing rat incisor enamel.
The amino-acid composition and total "protein" content of enamel particles dissected serially from the developing enamel of rat incisors have been determined. Changes in protein content and amino-acid composition occurred throughout all stages of development. The most obvious alterations occurred in the vicinity of a white opaque band. Here, protein was lost most rapidly and considerable changes in amino-acid composition occurred.


Digestion of chromatin with deoxyribonuclease II.
The action of DNAse II on DNA in chromatin was studied. The formation of acid-soluble products followed a two-phase kinetic curve. At the end of the first more rapid phase about 25% of DNA was degraded. Early in the degradation process DNA was converted into double stranded fragments, whose sizes were multiples of about 180 base pairs. As the degradation proceeded these fragments were reduced in size. After denaturation DNA from digested chromatin was resolved into discrete single stranded fractions, exact multiples of a ten-nucleotide length, forming a pattern very similar to that observed with DNAase I.chkova LV


Fertility after chemotherapy for testicular cancer.
Disseminated testicular cancer has largely become curable with cisplatin-based chemotherapy. The prospect of fertility after treatment is an important consideration for both patients and clinicians. While there may be an irreversible impairment of spermatogenesis at a cumulative cisplatin dose of greater than 400 mg/m2, a low sperm count does not necessarily appear to prevent fatherhood. This review summarizes currently available data on the effects of chemotherapy on male fertility and steps that can be taken to preserve fertility in this patient population.


Plasma gonadotropin levels in metformin-treated men with prediabetes: a non-randomized, uncontrolled pilot study.
Metformin was found to reduce elevated, but not normal, thyrotropin and prolactin levels. This non-randomized, uncontrolled pilot study investigated hypothalamic-pituitary-testicular axis activity in men with primary hypogonadism receiving metformin. The study population included 29 men with prediabetes, 10 of whom had been diagnosed with primary hypogonadism. Throughout the study, the participants were treated with metformin (2.55-3 g daily). Glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA1-IR), as well as circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, thyrotropin, prolactin, estradiol, and creatinine, were assessed at the beginning of the study and 16 weeks later. Both groups differed in baseline gonadotropin and testosterone levels. Fasting glucose, glycated hemoglobin, and HOMA1-IR were lower after than before metformin treatment. The changes in fasting glucose and HOMA1-IR were more pronounced in hypogonadal men than in subjects with testosterone levels within the reference range. Only in hypogonadal men, plasma concentrations of FSH and LH were lower at the end than at the beginning of the study. Levels of the remaining hormones remained unchanged throughout the study period. The reduction in FSH and LH levels correlated with their baseline levels and with the changes in HOMA1-IR. The results of our study suggest that metformin may decrease FSH and LH levels in men with hypergonadotropic hypogonadism.


How do social media and individual behaviors affect epidemic transmission and control?
In the outbreak of infectious diseases such as COVID-19, social media channels are important tools for the public to obtain information and form their opinions on infection risk, which can affect their disease prevention behaviors and the consequent disease transmission processes. However, there has been a lack of theoretical investigation into how social media and human behaviors jointly affect the spread of infectious diseases. In this study, we develop an agent-based modeling framework that couples (1) a general opinion dynamics model that describes how individuals form their opinions on epidemic risk with various information sources, (2) a behavioral adoption model that simulates the adoption of disease prevention behaviors, and (3) an epidemiological SEIR model that simulates the spread of diseases in a host population. Through simulating the spread of a coronavirus-like disease in a hypothetical residential area, the modeling results show that social media can make a community more sensitive to external drivers. Social media can increase the public's awareness of infection risk, which is beneficial for epidemic containment, when high-quality epidemic information exists at the early stage of pandemics. However, fabricated and fake news on social media, after a "latent period", can lead to a significant increase in infection rate. The modeling results provide scientific evidence for the intricate interplay between social media and human behaviors in epidemic dynamics and control, and highlight the importance of public education to promote behavioral changes and the need to correct misinformation and fake news on social media in a timely manner.


Summary of Research: Caregiver Involvement in MS: Duty or Disruption?
This Summary of Research summarizes a previously published discussion between people with multiple sclerosis (PwMS) and their caregivers and healthcare professionals (HCPs) about how to include caregivers in consultations and decisions about multiple sclerosis (MS) care. The aim of the discussion was to help HCPs to understand differences in these relationships so they can adapt the style of consultations to support everyone.


Identity of the photoproduct that causes lacI mutations in UV-irradiated Escherichia coli.
Estimates of the capacity of photoreactivation to act specifically on premutational lesions were obtained by conjugational transfer of an F' lac plasmid from a UV-irradiated, photoreactivated donor to a delta (pro-lac) recipient that had been UV irradiated and allowed to induce SOS functions for 30 min. This treatment reduced the frequency of induced lacI mutations by 70 to 80%, indicating that cyclobutane dimers cause most mutations in this system.


Another case for diet restriction: TAp73-expressing medulloblastomas are stunted by glutamine withdrawal.
Medulloblastomas are among the most common malignant brain cancers in the pediatric population and consist of at least four distinct subgroups with unique molecular and genetic features and clinical outcomes. In this issue of Genes & Development, Niklison-Chirou and colleagues (pp. 1738-1753) identify the p53 family member and p73 isoform TAp73 as a crucial factor causing glutamine addiction in aggressive medulloblastomas. Their findings pave the way for the use of glutamine restriction as an adjuvant treatment for TAp73-expressing medulloblastomas.


Imaging the cellular response to an antigen tagged interstrand crosslinking agent.
Immunofluorescence imaging is a standard experimental tool for monitoring the response of cellular factors to DNA damage. Visualizing the recruitment of DNA Damage Response (DDR) components requires high affinity antibodies, which are generally available. In contrast, reagents for the display of the lesions that induce the response are far more limited. Consequently, DDR factor accumulation often serves as a surrogate for damage, without reporting the actual inducing structure. This limitation has practical implications given the importance of the response to DNA reactive drugs such as those used in cancer therapy. These include interstrand crosslink (ICL) forming compounds which are frequently employed clinically. Among them are the psoralens, natural products that form ICLs upon photoactivation and applied therapeutically since antiquity. However, despite multiple attempts, antibodies against psoralen ICLs have not been developed. To overcome this limitation, we developed a psoralen tagged with an antigen for which there are commercial antibodies. In this report we describe our application of the tagged psoralen in imaging experiments, and the unexpected discoveries they revealed.


Re-description and molecular phylogeny of the free-swimming peritrichs Hastatella radians Erlanger, 1890 and H. aesculacantha Jarocki & Jakubowska, 1927 (Ciliophora, Peritrichia) from China.
The present work investigated Hastatella radians Erlanger, 1890 (type species), and H. aesculacantha Jarocki & Jakubowska, 1927, isolated from Chongming Island, Shanghai, China, based on light microscopy observations of live individuals, silver staining and molecular phylogeny methods. Hastatella radians is characterized by its size (about 30-75 μm long, 25-70 μm wide), two girdles of ectoplasmic processes, infundibular polykinety 3 (P3) composed of two rows of unequal length and terminating beyond adstomal end of P2, 8-22 transverse silverlines between peristome and trochal band, and 5-9 between trochal band and scopula. The infraciliature of H. aesculacantha is described for the first time, and we improved its diagnosis: cell size about 25-52 × 20-41 μm in vivo; four girdles of ectoplasmic processes; P3 two-rowed, outer row much shorter than inner one; 5-7 silverlines between peristome and trochal band and four or five between trochal band and scopula. Phylogenetic analyses based on SSU rDNA sequences revealed that Hastatella is monophyletic and has a close relationship to Astylozoon enriquesi.


Preliminary paleoecological insights from the Pliocene avifauna of Kanapoi, Kenya: Implications for the ecology of Australopithecus anamensis.
Fossil bird remains from the Pliocene hominin-bearing locality of Kanapoi comprise >100 elements representing at least 10 avian families, including previously undescribed elements referred to the 'giant' Pliocene marabou stork Leptoptilos cf. falconeri. The taxonomic composition of the Kanapoi fossil avifauna reveals an assemblage with a substantial aquatic component, corroborating geological evidence of this locality's close proximity to a large, slow-moving body of water. Both the taxonomic composition and relative abundance of avian higher-level clades at Kanapoi stand in stark contrast to the avifauna from the slightly older (∼4.4 Ma vs. 4.2 Ma) hominin-bearing Lower Aramis Member of Ethiopia, which has been interpreted as representing a mesic woodland paleoenvironment far from water. In general, the taxonomic composition of the Kanapoi avifauna resembles that from the Miocene hominoid-bearing locality of Lothagam (though Kanapoi is more diverse), and the aquatic character of the Kanapoi avifauna supports the idea that the environmental conditions experienced by Australopithecus anamensis at Kanapoi were markedly different from those experienced by Ardipithecus ramidus at Aramis. Additionally, the relative abundance of marabou stork (Leptoptilos) remains at Kanapoi may suggest a longstanding commensal relationship between total-clade humans and facultatively scavenging marabous. Additional avian remains from nearby fossil localities (e.g., the Nachukui Formation), ranging in age from 3.26 to 0.8 Ma, reveal the long-term persistence of an aquatic avifauna in the region.


The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts.
Live Borrelia burgdorferi were isolated from the blood and/or urine of white-footed mice (Peromyscus leucopus) collected on Shelter Island, New York, in 1984 and 1985. Prevalence of spirochetes in urine was consistently higher than in blood or both fluids simultaneously. Spirochetes remained viable for 18-24 hours in urine and were maintained in culture for one week. Mice removed from the field were spirocheturic for at least 13 months. One spirocheturic mouse developed spirochetemia one month after field removal indicating the pathogen can return to the peripheral circulation. Twenty-one kidneys from 22 mice had spirochetes in the interstitial areas and bridging the tubules. A positive correlation between Babesia microti infection and spirocheturia was seen. Although the mechanism of entry into the urine is unknown, B. microti infection may increase glomerular permeability. Babesia induced hematuria may provide possible nutrients to maintain spirochetes. Urine may provide a method for contact non-tick transmission of B. burgdorferi in natural rodent populations particularly during periods of nesting and/or breeding.


2-Amidino analogs of glycine-amiloride conjugates: inhibitors of urokinase-type plasminogen activator.
The relative non-toxicity of the diuretic amiloride, coupled with its selective inhibition of the protease urokinase plasminogen activator (uPA), makes this compound class attractive for structure-activity studies. Herein we substituted the C(2)-acylguanidine of C(5)-glycyl-amiloride with amidine and amidoxime groups. The data show the importance of maintaining C(5)-hydrophobicity. The C(5)-benzylglycine analogs containing either C(2)-acylguanidine or amidine inhibited uPA with an IC(50) ranging from 3 to 7 μM and were cytotoxic to human U87 malignant glioma cells.


Perception of alcohol policies by consumers of unrecorded alcohol - an exploratory qualitative interview study with patients of alcohol treatment facilities in Russia.
Over the last decade Russia has introduced various policy measures to reduce alcohol consumption and alcohol-related harm at the population level. Several of these policies, such as higher pricing and taxation or restrictions of availability, may not work in the case of unrecorded alcohol consumption; they may encourage consumers to switch to unrecorded alcohol and even increase consumption. In the present qualitative interview study we explore the perception of the recently implemented alcohol policies by patients diagnosed with alcohol dependence in two Russian cities in the years 2013-2014 and shed light on possible entry-points to prevention. Semi-structured in-depth expert interviews were conducted with 25 patients of state-run drug and alcohol treatment centers in two Russian cities in 2013 and 2014. The interviews were analyzed using thematic content analysis. All of the interviewed participants have consumed unrecorded at some point with the majority being regular consumers, mostly switching between recorded and unrecorded alcohol depending on the situation, as predominantly defined by available money and available sources of alcohol. Low price and high availability were reported as the main reasons for unrecorded consumption. Participants voiced a general mistrust of the recently implemented alcohol regulations and viewed them largely as ineffective. They expressed particular concerns over price increases and restriction of night sales of alcoholic beverages. Substantial shifts within the unrecorded alcohol market were reported, with a decreasing availability of home-made beverages in favor of alcohol surrogates in the form of non-beverage alcohol, medicinal and cosmetic compounds. At the same time consumption of home-made alcoholic beverages was seen as a strategy to avoid counterfeit alcohol, which was frequently reported for retail sale. Despite the alcohol policy changes in the last years in Russia, consumption of unrecorded alcohol remained common for people with alcohol dependence. Reduction of availability of unrecorded alcohol, first and foremost in the form of cheap surrogates, is urgently needed to reduce alcohol-related harm. Implementation of screening and brief interventions for excessive alcohol consumption in various contexts such as primary healthcare settings, trauma treatment services or the workplace could be another important measure targeting consumers of unrecorded alcohol.


Simultaneous determination of nifedipine and dehydronifedipine in human plasma by liquid chromatography-tandem mass spectrometry.
Quantitative analysis of therapeutic compounds and their metabolites in biological matrix (such as plasma, serum or urine) nowadays requires sensitive and selective methods to allow the determination of concentrations in the ng/ml range. A new on-line LC-MS-MS method using atmospheric pressure chemical ionisation (APCI) as interface for the simultaneous determination of nifedipine (NIF) and its metabolite in human plasma, dehydronifedipine (DNIF) has been developed. The compounds were extracted from plasma using solid-phase extraction (SPE) on disposable extraction cartridges (DECs). The SPE operations were performed automatically by means of a sample processor equipped with a robotic arm (ASPEC system). The DEC filled with phenyl modified silica was first conditioned with methanol and water. The washing step was performed with water. Finally, the analytes were successively eluted with methanol and water. The liquid chromatographic (LC) separation of NIF and DNIF was achieved on a RP-18 stationary phase (4 microm). The mobile phase consisted of methanol-50 mM ammonium acetate solution (50:50, v/v). The LC was then coupled to tandem mass spectrometry with an APCI interface in the positive ion mode. The method developed was validated. The absolute recoveries evaluated over the whole concentration range were 95+/-2% and 95+/-4% for NIF and DNIF, respectively. The method was found to be linear in the 0.5-100 ng/ml concentration range for the two analytes (r2 = 0.999 for both NIF and DNIF). The mean R.S.D. values for repeatability and intermediate precision were 2.9 and 3.0% for NIF and 2.2-4.7% for the metabolite. The method developed was successfully used to investigate the plasma concentration of NIF and DNIF in the pharmacokinetic studies.


Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy.
Dystrophin-deficient cardiomyopathy is a growing clinical problem without targeted treatments. We investigated whether nicorandil promotes cardioprotection in human dystrophin-deficient induced pluripotent stem cell (iPSC)-derived cardiomyocytes and the muscular dystrophy mdx mouse heart. Dystrophin-deficient iPSC-derived cardiomyocytes had decreased levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase. The dystrophin-deficient cardiomyocytes had increased cell injury and death after 2 hours of stress and recovery. This was associated with increased levels of reactive oxygen species and dissipation of the mitochondrial membrane potential. Nicorandil pretreatment was able to abolish these stress-induced changes through a mechanism that involved the nitric oxide-cyclic guanosine monophosphate pathway and mitochondrial adenosine triphosphate-sensitive potassium channels. The increased reactive oxygen species levels in the dystrophin-deficient cardiomyocytes were associated with diminished expression of select antioxidant genes and increased activity of xanthine oxidase. Furthermore, nicorandil was found to improve the restoration of cardiac function after ischemia and reperfusion in the isolated mdx mouse heart. Nicorandil protects against stress-induced cell death in dystrophin-deficient cardiomyocytes and preserves cardiac function in the mdx mouse heart subjected to ischemia and reperfusion injury. This suggests a potential therapeutic role for nicorandil in dystrophin-deficient cardiomyopathy.


Proximate composition, nutritional evaluation and functional properties of a promising food: Arabian wax Cissus (Cissus rotundifolia Forssk) leaves.
Cissus rotundifolia is a wild plant, extensively used during scarcity and famine; however, the information about its chemical and nutritional properties still limited. In this work, C. rotundifolia was evaluated for its chemical, nutritional and functional properties. The results revealed that C. rotundifolia mainly contained carbohydrates (72.54%), proteins (12.16%), ash (12.53%), dietary fiber (14.10%), in addition to adequate amounts of essential amino acids and minerals. Fructose, glucose, galactose, and arabinose were the major monosaccharides with a percentage of 23.32, 13.60, 1.24, and 0.25 g/100 g DW, respectively. Furthermore, it was found that C. rotundifolia contained important vitamins, including thiamin (5.37 mg/100 g DW), riboflavin (1.19 mg/100 g DW), pyridoxine (0.46 mg/100 g DW) and folic acid (0.20 mg/100 g DW). The findings of functional properties revealed good water and oil absorption capacities of 2.74 and 1.63 g/g, respectively. Foaming capacity and water solubility index were 14 and 18.74%, respectively. From these results, it can be stated that C. rotundifolia has high nutritional values, which could be used widely in food applications.


A multiyear survey of helminths from wild saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarins.
The establishment of baseline data on parasites from wild primates is essential to understand how changes in habitat or climatic disturbances will impact parasite-host relationships. In nature, multiparasitic infections of primates usually fluctuate temporally and seasonally, implying that the acquisition of reliable data must occur over time. Individual parasite infection data from two wild populations of New World primates, the saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarin, were collected over 3 years to establish baseline levels of helminth prevalence and parasite species richness (PSR). Secondarily, we explored variation in parasite prevalence across age and sex classes, test nonrandom associations of parasite co-occurrence, and assess the relationship between group size and PSR. From 288 fecal samples across 105 individuals (71 saddleback and 34 emperor tamarins), 10 parasite taxa were identified by light microscopy following centrifugation and ethyl-acetate sedimentation. Of these taxa, none were host-specific, Dicrocoeliidae and Cestoda prevalences differed between host species, Prosthenorchis and Strongylida were the most prevalent. Host age was positively associated with Prosthenorchis ova and filariform larva, but negatively with cestode and the Rhabditoidea ova. We detected no differences between expected and observed levels of co-infection, nor between group size and parasite species richness over 30 group-years. Logistic models of individual infection status did not identify a sex bias; however, age and species predicted the presence of four and three parasite taxa, respectively, with saddleback tamarins exhibiting higher PSR. Now that we have reliable baseline data for future monitoring of these populations, next steps involve the molecular characterization of these parasites, and exploration of linkages with health parameters.


A peptide antibody for rapid screening of Streptomyces species producing phospholipase D.
By examining the conserved regions in the protein sequences of eight different Streptomyces phospholipase Ds (PLD) reported so far and the X-ray crystallographic structure of a Streptomyces PLD, we designed a peptide sequence, DPANRGAVGSGGYSQIKSL, for the screening of microorganisms producing PLD. In the enzyme-linked immunosorbent assay using a mouse antibody raised against the designed peptide, we recovered seven producing strains out of 128 soil isolates.


High-throughput comprehensive analysis of D- and L-amino acids using ultra-high performance liquid chromatography with a circular dichroism (CD) detector and its application to food samples.
A rapid and comprehensive analytical method for D- and L-enantiomers of proteinogenic amino acids was developed using ultra-high performance liquid chromatography (UHPLC) equipped with a circular dichroism (CD) detector. Pre-column derivatization reagents were examined for enhanced sensitivity and selectivity for UV and CD detection: 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was selected. The method, using a CD detector, does not require separation of optical isomers on a column to calculate the enantio ratio (%D) using the g-factor value and produces a simple chromatogram in comparison to other reported methods. Using this advantage, combined with UHPLC technology, analysis time for the derivatized proteinogenic amino acids was within 5.5 min. The UV detection limit was 4.9-23 pmol/injection and the CD detection limit was 11-64 pmol/injection. The method was applied to the analysis of D- and L-amino acids in food samples. D-Ala, D-Asp, D-Glu and D-Ser were detected at high concentrations in some Japanese black vinegars, fermented milks and yogurts. The results were identical to the results determined by the OPA method. We suggest the UHPLC-CD method would be useful in screening the D-amino acid content of foods and in helping to clarify the importance and reason for the presence of D-amino acids in foods.


12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation.
This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months. The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported. Patients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety. Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was -2.3 mm Hg (95% confidence interval [CI]: -5.9 to 1.3 mm Hg; p = 0.201) for dASBP, -6.3 mm Hg (95% CI: -11.1 to -1.5 mm Hg; p = 0.010) for office SBP, and -3.4 mm Hg (95% CI: -6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography. Despite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.


Potentially inappropriate medication use in Indian elderly: comparison of Beers' criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions.
To compare Beers' criteria (BC) and Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) for prevalence, specificity, sensitivity and predictors for potentially inappropriate medication (PIM) use. Patients aged ≥ 60 years from medicine wards of a tertiary care hospital were included. Comparisons between BC and STOPP were made using Pearson's χ(2) -test for categorical variables and Mann-Whitney U-test for continuous variables. Specificity and sensitivity were assessed by using 2 × 2 contingency table. Bivariate analysis and subsequent multivariate logistic regression was used to identify the predictors of PIM use. In the 540 patients included, prevalence of PIM use as per BC and STOPP was 24.6% and 13.3%, respectively. Sensitivity and specificity of BC in detecting PIM was 0.65 and 0.53, respectively. Considering the diagnoses/conditions, sensitivity and specificity of BC was 0.12 and 0.48, respectively, whereas independent of diagnoses/conditions, corresponding values were 0.75 and 0.54. PIM as per BC and STOPP accounted for 11 and 6 adverse drug reactions (ADR), respectively. Medications not listed in BC or STOPP were more likely to be associated with ADR. Multiple diseases (≥ 4) and use of more drugs during hospital stay (10-14) predicted PIM use as per BC, whereas age (60-74 years) predicted PIM use as per STOPP. Overall, BC is useful in the detection of PIM use independent of diagnoses/conditions, whereas STOPP is useful in detection of PIM use considering the diagnoses/conditions. There is a need for consensus on using the tool for detection of PIM use in Indian elderly.


Chronic mechanical circulatory support: rehabilitation, low morbidity, and superior survival.
Because of donor scarcity, 12 (39%) of a series of 31 Novacor left ventricular assist system recipients required mechanical circulatory support for an average of 125 days before transplantation (range, 61 to 303 days). Ten received a heart transplant and all survived to discharge. Two died of infection before transplantation after 93 and 303 days of support. Significant reductions were noted from preimplantation values of right and left cardiac filling pressures. Right ventricular ejection fraction and cardiac index increased. The 4-month actuarial freedom from infection during support was 75%. Three patients benefited from chronic outpatient housing for 5, 18, and 131 days, respectively, with improvements in quality of life measures. Ten chronically supported patients participated in an intensive rehabilitative exercise program resulting in an improvement of New York Heart Association class from IV to I in 9 patients. Mean oxygen consumption, which was 10 mL.kg-1.min-1 30 days after implantation (mean exercise time, 10 minutes) had risen to 15 mL.kg-1.min-1 before transplantation (mean exercise time, 16 minutes). This series suggests that long-term circulatory support is compatible with low morbidity, significant physical and hemodynamic rehabilitation, and an outpatient setting.


The Mediterranean diet increases glucagon-like peptide 1 and oxyntomodulin compared with a vegetarian diet in patients with type 2 diabetes: A randomized controlled cross-over trial.
To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.


Activation of macrophage-stimulating protein by human airway trypsin-like protease.
Macrophage-stimulating protein (MSP) circulates as a proform protein and requires proteolytic processing for activation. Respiratory ciliated cells express the MSP receptor, recepteur d'origine nantais (RON), at the apical surface, which reportedly has an important role in ciliary function. Like RON, human airway trypsin-like protease (HAT) is also expressed at the apical surface of ciliated cells. Here we show that HAT cleaves proMSP at the physiological activation site, Arg483-Val484. MSP processed by HAT could induce chemotactic responses and morphological changes of peritoneal macrophages. In human respiratory epithelial cells, knock down of HAT expression reduced proMSP processing and RON autophosphorylation. We suggest that HAT is important for MSP-RON signaling in the respiratory tract.


Stability of radioiodinated ferritin.
Ferritin which had been radioiodinated using chloramine T exhibited marked instability on storage at 4 degrees C. Both [125I]human liver and heart ferritins showed a similar rate of decline in immunoreactivity (t 1/2 = 20-23 days) indicating that deterioration with storage was not a function of isoferritin composition. The decrease in radioactivity associated with ferritin was due not only to loss of 125I from the molecule but also to protein degradation as shown by enzyme-linked immunoassay and gel filtration. The degradation products had an Mr of at least 69,000 although low Mr material could be identified by gel filtration when a marked reduction in immunoreactivity had occurred. Ferritin instability was much more pronounced than when other proteins such as immunoglobulin and albumin were radioiodinated with chloramine T. These observations indicate that when performing in vivo and in vitro studies with labeled ferritin, degradation of the protein during storage should be carefully monitored and the protein repurified before use.


Acute intrathoracic gastric volvulus with retrograde gastric intussusception: A case report of a rare surgical emergency with review of the literature.
The gastric volvulus is a rare condition in which the stomach, or part of it, rotates on its axis, for over 180°, constituting a surgical emergency. Even more rare is gastro-gastric intussusception. A delay in their diagnosis and treatment can have fatal consequences PRESENTATION OF CASE: An 82-year-old woman was admitted to the Surgery Unit with a two-day history of abdominal pain associated at first with coffee vomiting and, subsequently, with unproductive retching and oligoanuria. Physical examination showed severe dehydration, fever, at the abdominal level, palpation caused a marked tenderness of all quadrants, with signs of peritonism. Laboratory test showed showed neutrophilic hyperleukocytosis and high C reactive protein level. Abdominal computed tomography revealed an acute intrathoracic gastric volvulus and a gastrogastric intussuception. The patient was submitted to exploratory laparotomy, subtotal gastrectomy with Roux en Y anastomosis and simple plastic of the esophageal hiatus. At the end of the surgery, however, the patient died of your septic shock. The traditional treatment for a patient with acute gastric volvulus is an immediate surgical intervention to derotate the stomach and prevent vascular insufficiency. In the presence of necrosis or gastric perforation, resection should be performed. The few cases of gastrogastric intussusception described in the literature have been treated with sub-total gastrectomy and gastro-jejunal anastomosis. Any delay in diagnosis and treatment can prove fatal. Intrathoracic Gastric Volvulus and, even more, retrograde gastrointestinal intussusception are very rare pathologies, difficult to diagnose.


Experiences of type 2 diabetes in sub-Saharan Africa: a scoping review.
The prevalence of diabetes in Sub-Saharan Africa (SSA) is growing rapidly. Qualitative research on experiences of type 2 diabetes in SSA is emerging, but no qualitative synthesis has been attempted. This scoping review aims to redress this lack of synthesis and to extract policy-relevant suggestions from the literature. Scoping review methodology was employed. Eleven online databases were searched (CINAHLplus, Cochrane Library, EBESCOhost, GALE Group, MEDLINE, Pro-Quest, Pscyhinfo, Pubmed, SCOPUS, Web of Science, WorldCat), using terms designed to identify qualitative studies of experiences of diabetes in SSA. Findings from records identified in the search were analysed inductively in NVivo 10 in three stages, to produce an analytical synthesis of studies of diabetes experiences in SSA. Searches were conducted in 2017 and identified 2743 records, which were reduced to 21 after screening. The earliest identified record was published in 2003 and there was a clustering of records published between 2014 and 2016. The 21 records were based in eight SSA countries: Cameroon, Ethiopia, Ghana, Senegal, South Africa, Tanzania, Uganda, and Zimbabwe. A majority of the studies were conducted in Ghana (5) and South Africa (5), limiting the generalisability of our findings.The analytical synthesis produced five themes: identifying type 2 diabetes (how participants conceptualise and position their illnesses); hybridity of diabetes care (how multiple forms of care are often blended and/or pursued concurrently); impediments, improvisation and diabetes management (describing challenges faced, how these are responded to and management via diet and physical activity); sources of support (who supports participants and how); and diabetes and HIV/AIDs (the ways in which the two conditions are sometimes confused and how stigma is often experienced). The experiences of people with type 2 diabetes in SSA are under-researched across the region, pointing to a gap in knowledge. Interpreting our analytical synthesis, we suggest three priority areas for policy makers and implementers. Firstly, uncertainties relating to access to diabetes treatment need to be reduced. Secondly, more needs to be done to acknowledge and alleviate the economic struggles that those with diabetes face. Finally, high-quality information and education would improve recognition and management of the condition.


Enhancement of the action of alkylating agents by single high, or chronic low doses of misonidazole.
Misonidazole (MISO) given as a large single dose enhanced the action of cyclophosphamide (Cy) and melphalan (L-PAM) in two mouse tumours. Below a dose of about 500 mg kg-1 it had no chemosensitizing effect. When MISO was given as a series of small doses by repeat injection over an 8 h period, in order to stimulate human pharmacokinetics, it significantly enhanced the action of Cy in the SA F tumour. It also enhanced the action of Cy and L-PAM in the WHFIB tumour as assayed by tumour cell survival in vitro following treatment in vivo but not when the assay was tumour growth delay. There was no enhancement by MISO of the leukopenia due to Cy or L-PAM. The results suggest that, in some tumours there may be benefit from the combination of clinically relevant MISO doses with alkylating agents. The leucopenia induced by these agents should not be enhanced by the MISO.


Erratum: Amende.
[This corrects the article on p. 556 in vol. 8.][This corrects the article on p. 564 in vol. 8.].


The nude mouse. A possible experimental model for investigation of human thyroid tissue.
The effect of transplanting hyperfunctioning human thyroid tissue to athymic, nude mice was explored. The thyroid tissue was obtained from a patient with diffuse, thyrotoxic goiter preoperatively treated with a beta-adrenoreceptor blocker. One transplant was placed in each groin of 4 nude mice. Light microscopy after 4 weeks showed that transplants consisted mainly of typical follicles; capillaries were common at the periphery of the transplant but not in between the follicles. The ultrastructure of the follicle cells in the transplants was similar to that of follicle cells in general. All 8 transplants accumulated 125I as revealed by external counting; the uptake in each transplant 24 h after administration of radioiodine was 4-25% of that in the thyroid of the transplanted mouse. The release of radioiodine, measured during a period of 14 days, from the thyroid of a transplanted mouse was delayed as compared to a nontransplanted control; this indicates that the mouse thyroid activity was suppressed due to hormone production in the transplants. Electron microscopic autoradiography 24 h after injection of 125I showed that protein-bound label in transplants was located mainly in follicle lumens. The radioiodine was incorporated in thyroglobulin as demonstrated by separation of soluble proteins from transplants by sucrose density gradient centrifugation. The present study shows that human thyroid tissue can be transplanted to nude mice with maintained structural and functional properties. Transplantation of human thyroid tissue might be a useful model for studies of thyroid diseases.


The 24-h distribution of falls and person-hours of physical activity in the home are strongly associated among community-dwelling older persons.
Most research on falls among older persons focuses on health-related factors that affect the ability to maintain balance. The objective of the study is to determine the association between physical activity and occurrence of falls among community-dwelling older persons. The distribution of falls and person-hours of physical activity in the home over 24 h was compared. The falls data (n=501) were extracted from a pooled dataset of three follow-up studies conducted between 1994 and 2005 (n=3587). The 1995 Dutch National Time-Budget Survey provided hour-by-hour information on activities performed by older individuals (n=459) in the home; this sample was representative for the Netherlands. The association between the 24-h distribution of falls and physical activity and the risk of falling (the ratio between the distribution of falls and physical activity) were determined. Participants were community-dwelling older persons aged 65 years and older. More physical activity was positively associated with more falls (Spearman correlation=.89, p<.000). The risk of falling at night (1 a.m.-6 a.m.) was almost eight times higher compared to 7 a.m.-12 p.m. Physical activity is strongly associated with the number of falls in the home, measured over 24 h. Older persons may be at increased risk of falling if they are encouraged to become more physically active, or if they often get out of bed at night. Thus in addition to health-related factors, changes in level of physical activity should also be taken into account when estimating a person's risk of falling.


Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence.
A growing number of patients with mood disorders are using complementary and alternative medicine (CAM) interventions. In this paper, we review the published scientific evidence on the benefits and risks of CAM for the treatment of patients with bipolar disorder. Since very few studies of CAM have involved patients with bipolar disorder, most available evidence is derived from trials conducted in patients with major depressive disorder. The use of omega-3 fatty acids has been studied in two controlled studies in bipolar disorder while St. John's wort (Hypericum perforatum), S-adenosyl-l-methionine (SAMe), and acupuncture have been studied in a series of randomized controlled trials in patients with major depression. Overall, the best evidence supports the use of St. John's wort for the treatment of mild to moderate depression. SAMe may also be effective for depression. However, both of these products have the potential to induce mania; the extent of this risk needs to be quantified. St. John's wort can also interact with a variety of medications. Evidence regarding the benefits of omega-3 fatty acids or acupuncture is inconsistent. Data regarding other CAM interventions (e.g., aromatherapy massage, massage therapy, yoga) are almost entirely lacking. In conclusion, better studies are needed before CAM interventions can be recommended to patients with bipolar disorder. In the meantime, patients need to be informed about the possible risks associated with the use of these interventions.


Early soft tissue ingrowth into porous block hydroxyapatite.
A dog model was used to determine the rate of soft tissue infiltration into porous block hydroxyapatite (PBHA) in order to provide a scientific basis for treatment of exposed implants. Ten mongrel dogs underwent alveolar ridge augmentation with PBHA and were killed at various times up to 21 days. Significant soft tissue ingrowth had occurred by 14 days and was complete by day 21. Bone formation was also seen as early as 14 days.


Transient kinetics of the interaction of actin with myosin subfragment-1 in the absence of nucleotide.
The kinetics of the association of actin with myosin subfragment-1 (S1) has been studied by using S1 labeled at the sulfhydryl group SH1 with 5-(iodoacetamido)fluorescein (S1-AF). Upon rapid mixing in a stopped-flow apparatus, the fluorescence intensity of the fluorescein moiety increased by 50%, followed by a slower increase that was well resolved. This slow phase of the fluorescence change could not be fitted to either a monoexponential or a biexponential function, but it could be fitted to a sum of three exponential terms yielding three observed first-order rate constants (lambda i). The dissociation of acto.-(S1-AF) was studied by displacement of S1-AF from the complex with native S1. The dissociation kinetics was characterized by a single rate constant (approximately 0.012 s-1 at 20 degrees C), and this constant was independent of S1 concentration. Together with previous equilibrium data that were obtained under identified conditions for formation of acto-subfragment-1 (Lin, S.-H., and H. C. Cheung. 1991. Biochemistry. 30:4317-4323), a six-state two-pathway model is proposed as a minimum kinetic scheme for formation of rigor acto.S1. In this model, unbound subfragment-1 exists in two conformational states (S1' and S1) which are in equilibrium with each other, one corresponding to the previously established low-temperature state and the other to the high-temperature state. Each subfragment-1 state can interact with actin to form a collision complex, followed by two isomerizations to form two acto-subfragment-1 states (A.S1' and A.S1). Both isomerizations were visible in stopped-flow experiments. Two special cases of the model were considered: 1) a rapid pre-equilibration of the initial collision complex with actin and S1, and 2) trace accumulation of the collision complex. The first case required that the three combinations of the three observed rate constants be independent of actin concentration. The data were incompatible with this approximation. The other special case required that the sum of the lambda i vary linearly with actin concentration and the other two combinations of lambda i vary with actin concentration in a quadratic fashion. The present data were in agreement with the second case. At 20 degrees C and in 60 mM KCl, 2 mM MgCl2, 30 mM 2-([-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino)ethanesulfonic acid, and pH 7.5, the biomolecular association rate constants for the interaction of actin with S1' and S1 were 8.58 x 10(5) and 1.11 x 10(6) M-1 s-1, respectively.