Graft-versus-host disease is associated with a lower relapse incidence after hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.
To determine the graft-versus-leukemia effect after hematopoietic stem cell transplantation (HSCT), we studied 199 patients with acute lymphoblastic leukemia who underwent transplantation at Huddinge University Hospital between 1981 and 2001. Seventy-four patients were in first complete remission (CR1), and 125 were in later stages of the disease. Most patients had an HLA-identical sibling donor. Conditioning consisted mainly of total body irradiation and cyclophosphamide, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Acute GVHD developed in 143 patients and chronic GVHD in 67. The 5-year probability of relapse and relapse-free survival (RFS) were 32% and 49%, respectively, in patients in CR1, as compared with 53% and 33% in those with more advanced disease. In the multivariate risk factor analysis of relapse, we found that the absence of chronic GVHD (P<.001), absence of herpes simplex virus infection after HSCT (P=.003), combination prophylaxis with methotrexate and cyclosporine (P=.01), and >6 weeks from the diagnosis to CR (P=.025) were independent risk factors for relapse after HSCT. Factors associated with a better relapse-free survival were chronic GVHD (P<.001), ABO blood group mismatch (P=.006), younger patient age (P=.01), and an HLA-matched donor (P=.01). The association between herpes simplex virus infection and a low frequency of relapse is a new observation and may indicate that viral antigens play a role in the induction of an antileukemic effect.


Assessment of potential aluminum chelators in an octanol/aqueous system and in the aluminum-loaded rabbit.
Aluminum (Al) solubilization from Al borate and its distribution in an octanol/aqueous system (Do/w) were determined in the absence and presence of 12 potential Al chelators. Citrate, N,N'-bis-(2-hydroxybenzyl)ethylenediamine- N,N'-diacetic acid (HBED), cyclohexane-1,2-diaminotetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid (NTA), desferrioxamine, and ethylenediamine-N,N'-bis(2-dihydroxyphenylacetic acid) (EDDHA) were 55 to over 100% efficient in solubilizing equimolar amounts of Al. Tetracycline, EDTA, and 2,3-dihydroxybenzoic acid (DHBA) were less than 20% efficient. 1,4-Dioxane and fluoride were ineffective. The Do/w of Al averaged 0.005. The Do/w of the Al.chelator complex was generally less than that of Al, except for HBED and tetracycline (0.04 and 0.96, respectively). The Do/w of DHBA, desferrioxamine, EDDHA, and HBED were not influenced by Al, but tetracycline became more lipophilic. These compounds were tested for their ability to increase urinary Al excretion in Al-loaded rabbits. Chelators were given po weekly beginning 2 weeks after Al loading. Urine was obtained hourly from 3 hr prior to 6 hr after chelator administration and analyzed for Al. Fluoride and tetracycline (450 and 4500 mumol/kg) and citrate, NTA, EDTA, CDTA, DTPA, DHBA, HBED, and 1,4-dioxane (150 and 1500 mumol/kg) were ineffective. Following HBED administration, some of the Al-loaded rabbits died, presumably due to redistribution of Al within the rabbit. Following DTPA administration, some of the Al-loaded rabbits died, presumably due to DTPA. Oral EDDHA (1500 mumol/kg) significantly increased urinary Al excretion. EDDHA and desferrioxamine (150 mumol/kg) were administered by po, sc, and iv routes and were found to have comparable potency. The in vitro results may explain some of the in vivo findings. The in vitro methods may be useful to screen out compounds with no chelation potential. EDDHA-like compounds may have potential as alternatives to desferrioxamine in the prevention or treatment of Al accumulation and Al-induced toxicity.


Diethylhydrogensilyl-cyclic diethylsilylene derivatives in gas chromatography-mass spectrometry of prostanoids. III. F alpha-prostaglandins and thromboxane B2 derivatives.
The gas chromatographic (GC) and GC-mass spectrometric properties of the diethylhydrogensilyl-cyclic diethylsilylene (DEHS-DES) derivatives of prostaglandin (PG) F1 alpha methyl ester, PGF2 alpha methyl ester, 6-keto-PGF1 alpha methyl ester-alkyloxime and thromboxane (TX) B2 methyl ester-alkyloxime and the DES derivative of 13,14-dihydro-15-keto-PGF2 alpha methyl ester-alkyloxime were studied. When the ketonic PGs and TXB2 were converted into their methyloxime derivatives, the methylene unit values of these five prostanoid derivatives were slightly greater than those of the corresponding dimethylethylsilyl ether derivatives. When the ketonic PGs were converted into their corresponding ethyloxime derivatives, baseline separation was achieved in 20 min by use of a methylsilicone cross-linked fused-silica capillary column. The mass spectra of these derivatives were characterized by the ion at m/z 157 for F alpha prostaglandins and m/z 269 for TXB2. The major fragmentations were directed by the DES group, and other fragmentations common to the prostanoid derivatives were losses of an ethyl radical at the silicon atom, C5H11 hydrocarbon fragment, diethylhydrogensilanol and C15-C20 hydrocarbon fragment. The mass fragmentations of these prostanoid derivatives are briefly discussed. GC with high-resolution selected-ion monitoring was carried out for the TXB2 derivative at a resolution of 8000 by monitoring the ion at m/z 269.1573. A 25-pg amount of this derivative showed a well shaped doublet with a signal-to-noise ratio of more than 300:1.


Cerebral Malaria in a Patient with Recent Travel to the Congo Presenting with Delirium: A Case Report.
Cerebral malaria, a syndrome of altered consciousness, is a rare and severe neurologic complication resulting from Plasmodium falciparum. Historically, cerebral malaria has been seen more frequently in children rather than adults. To complicate the diagnosis, cerebral malaria has few specific symptoms and neurologic findings can vary with each case. We describe a case of a 61-year-old male who returned from the Democratic Republic of Congo and presented to the emergency department with dehydration, fatigue, and intermittent confusion. He was ultimately diagnosed with cerebral malaria caused by P. falciparum. Even with close monitoring and appropriate treatment, cerebral malaria carries a severe risk of long-term neurocognitive deficits and a high mortality rate.


Movement patterns of an Australian chrysomelid beetle in a stand of two Eucalyptus host species.
We examined the movements of Chrysophtharta hectica, a eucalypt-feeding chrysomelid beetle in New South Wales, Australia, in relation to the beetle's sex, age and life-history, and to attributes of its Eucalyptus host plants. Beetle movements within the site were not influenced by beetle age or sex, but may be related to generation. Beetle distributions on the two host plant species, Eucalyptus stellulata and E. pauciflora, were generally clumped. Some of this clumping resulted from preference for E. stellulata over E. pauciflora. Clumping of beetles also occurred within host plant species; some plant individuals were consistently heavily used by beetles over the course of three years. We examined nutritional, spatial and biomass attributes of plants and found plant height and foliage production to be the best predictors of beetle numbers.


[Campylobacter pylori gastritis: review of diagnostic methods].
The presence of Campylobacter pylori in gastric mucosa is a proof of active gastritis. Diagnostic methods are based on endoscopy: culture--histology--cytology--urease test, or on noninvasive tests: C14 urea breath test and serology. The principles, results (sensitivity--specificity), advantages and problems of each test are discussed as well as the choice of a diagnostic method. In practice, we recommend the use of two methods, a morphological one (histology or cytology) and another based on bacterial activity (urease test or culture).


Difference in presentation, outcomes, and hospital epidemiologic trend of COVID-19 among first, second, and third waves: a review of hospital records and prospective cohort study.
This study aimed to examine the differences in epidemiologic and disease aspects among patients with coronavirus disease-19 (COVID-19). The authors reviewed the hospital records between April 2020 and September 2021 and followed up on the patients for post-COVID complications. Older adult patients were predominantly affected during the third wave, and middle-aged patients were predominantly affected during the first and second waves. Men were predominantly admitted, considering the three waves, although more women were admitted in the second wave. Cough was more common in the second and third waves than in the first wave 522 (59.7%). Respiratory distress was the most common in the third wave, 251(67.1%), and least common in the first wave, 403 (46.1%). Anosmia was more common in the third wave 116 (31.2%). In the third wave, patients presenting in a critical state 23 (6.2%) and with severe disease 152 (40.8%) were more common. The hospital admission median (IQR) was longer in the first wave, 12 (8-20), than in other waves. More patients were admitted in the first wave (52%) than in the other waves, and patients received more oxygen in the third wave (75%) than in the other waves. Death occurred more commonly in the first wave (51%) than in the other waves. The positivity rate was higher in the third wave (22.8%) than in the other waves. In the third wave, the positivity rate was higher in women (24.3%) than in men. Post-COVID cough increased in the second wave, and fatigue was higher in the third wave than in the other waves. Tiredness and memory loss were greater during the second wave than in other waves. The authors found differences in the presentation, outcomes, and hospital epidemiologic trend of COVID-19 among the three waves.


Pay or conditions? The role of workplace characteristics in nurses' labor supply.
Empirically rigorous studies of nursing labor supply have to date relied on extant secondary data and focused almost exclusively on the role of pay. Yet the conditions under which nurses work and the timing and convenience of the hours they work are also important determinants of labor supply. Where there are national pay structures and pay structures are relatively inflexible, as in nursing in European countries, these factors become more important. One of the principal ways in which employers can improve the relative attractiveness of nursing jobs is by changing these other conditions of employment. This study uses new primary data to estimate an extended model of nursing labor supply. It is the first to explore whether and how measures of non-pecuniary workplace characteristics and observed individual (worker) heterogeneity over non-pecuniary job aspects impact estimates of the elasticity of hours with respect to wages. Our results have implications for the future sustainability of an adequately sized nurse workforce and patient care especially at a time when European healthcare systems are confronted with severe financial pressures that have resulted in squeezes in levels of healthcare funding.


Payer perceptions on the use of economic models in oncology decision making.
BACKGROUND: To support oncology formulary decisions, especially with accelerated regulatory approvals and niche populations, payers desire data beyond what regulators review. Economic models showing financial impact of treatments may help, but data on payers' use of economic models in oncology are limited. OBJECTIVE: To assess payer perceptions regarding use of economic models in informing oncology formulary decisions. METHODS: A multidisciplinary steering committee involving health economists and payers developed a survey containing singleanswer, multiple-answer, and free-response questions. The pilot survey was tested at a mini-advisory board with 5 US payers and revised based on feedback. In February 2020, the survey was distributed to 221 US payers through the AMCP Market Insights program and 10 additional payer panelists, who were invited to discuss survey results. Results were presented primarily as frequencies of responses and evaluated by plan size, type of health plan, and geography (regional vs national). Differences in categorical data responses were compared using Pearson chi-square or Fisher's exact tests. Two-tailed values were reported and an alpha level of 0.05 or less was used to indicate statistical significance. RESULTS: Overall, 106 of 231 payers completed the survey (45.9%); 45.5% represented small plans (< 1 million lives), and 54.5% represented large plans (≥ 1 million lives). Respondents were largely pharmacists (89.9%), and 55.6% indicated that their job was pharmacy administrator. Payers indicated moderate/most interest in cost-effectiveness models (CEMs; 85.3%) and budget impact models (BIMs; 80.4%). Overall, 51.6% of respondents claimed oncology expertise on their pharmacy and therapeutics committees. Large plans were more likely to have expertise in reviewing oncology economic models than small plans (55.6% vs 31.1%, P = 0.015). The most common reasons for not reviewing economic models included "not available at time of review" (44.1%) and "potential bias" (38.2%). Overall, 43.1% of payers conduct analyses using their own data after reviewing a manufacturer-sponsored economic model. To inform formulary decisions, 62.7% of payers use BIMs and 66.7% use CEMs sometimes, often, or always. When comparing therapies with similar safety/efficacy profiles, 68.6% of payers reported economic models as helpful a moderate amount, a lot, or a great deal. Over one-third of payers (37.3%) were willing to partner with manufacturers on economic models using their plans' data. Payers valued preapproval information, data on total cost of care, and early access to models. Concerns remained regarding model transparency and assumptions. CONCLUSIONS: Most US payers reported interest in using economic models to inform oncology formulary decision making. Opportunities exist to educate payers in assessing economic models, especially among small health plans. Ensuring model availability at launch, transparency in model assumptions, and payer-manufacturer partnership in model development may increase the utility of oncology economic models among US payers. DISCLOSURES: Pfizer provided funding for this research, and Pfizer employees led the development of the survey instrument, were involved in the analysis and interpretation of the data, and contributed to the manuscript as authors. Arondekar and Niyazov are employed by Pfizer. Biskupiak, Oderda, and Brixner are managers of Millcreek Outcomes Group and were paid as consultants on this project. Burgoyne was a consultant for Pfizer on this project.


Molecular Recognition of Pyrophosphate with Extended Bis(Zn(II)-DPA) Derivatives.
A series of pyrophosphate (PPi) receptors were synthesized, and their binding affinities toward both PPi and adenosine triphosphate were evaluated in N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid-buffered solution. The presence of two hydrogen bond donors slightly retarded the reaction rate of anionic guest exchange, while four had a significant retardation effect. A macrocyclic receptor, 17, exhibited superior selectivity toward PPi compared with acyclic receptors, presumably due to effective steric interactions. Isothermal titration calorimetry experiments and potentiometric titration experiments revealed the effect of the substituent structure on the degree of anion guest stabilization and the deprotonation of water molecules bound to zinc(II) ions, as well as the guest binding thermodynamics.


Proglumide peptides and CCK antagonistic action in hog duodenal circular muscle.
New proglumide peptides were synthesized and their inhibitory activity against the cholecystokinin (CCK)-induced relaxation was tested in duodenal circular muscles of hogs in order to locate the active moiety. Isotonic tension is reported as a percentage of the relaxation induced by CCK-4 (4.23 microM) or by Ca-free EGTA (2 mM). In R1-CONHCH(CH2CH2CO-R2)CON(CH2CH2CH3)2, P2-II(R1 = PhCH2O, R2 = Phe33-NH2), its D isomer and P3-I (R1 = Ph, R2 = Asp32-Phe33-NH2) had potent antagonistic activity (IC50 = 47.9 (32.4-72.4) microM, 25.1 (10.0-61.7) microM and 186 (141-240) microM, respectively). Benzotript, from another group of CCK antagonists had an IC50 of 52.5 (40.7-67.6) microM. P2-II (49 microM) or its D isomer (19.6 microM) antagonized non-competitively, and P3-I (168 microM) and benzotript (58.4 microM) antagonized competitively the CCK-4-induced relaxation. P3-I (84 or 168 microM) also antagonized competitively the CCK-8-induced relaxation. The amino acids of Tyr27, Trp30 and Phe33, separately, play important roles for agonist activity for relaxation. Tyr27 is the main relaxing group, Trp30 an antagonistic one and Phe33 is another relaxing one. In the proglumide skeleton, N,N-dipropylglutaramic acid acts like Trp30. Agonist, partial agonist and antagonist activities are exerted by these three groups and bulky substituents.


First-trimester screening for Down syndrome with ductus venosus Doppler studies in addition to nuchal translucency and serum markers.
To estimate the improvement in screening efficiency when fetal ductus venosus Doppler studies are added to existing first-trimester Down syndrome screening protocols. Statistical modelling was used with parameters derived from prospective ductus venosus studies and from the published literature. The pulsatility index for veins (PIV), was determined in the fetal ductus venosus for 3706 unaffected and 25 Down syndrome pregnancies at 10-14 weeks' gestation. Concurrent nuchal translucency measurement and maternal serum pregnancy associated plasma protein A and free-beta human chorionic gonadotrophin were also measured. The median PIV in Down syndrome was 1.70 times higher than in unaffected pregnancies (95% confidence interval 1.36-2.12). PIV levels followed an approximately log Gaussian distribution with log(10) standard deviations of 0.193 and 0.076 in Down syndrome and unaffected pregnancies. There were no statistically significant correlations between PIV and the other markers. Modelling predicts that for a fixed 5% false-positive rate, the addition of PIV to nuchal translucency alone will increase the detection rate from 76 to 85%, and combined with serum markers, from 88 to 92%. For a fixed 85% detection rate, the false-positive rate reduced from 15 to 4.8% and from 3.2 to 1.2% respectively. Ductus venosus Doppler studies can substantially improve Down syndrome screening efficiency.


The effects of operative stress on the coagulation profile.
There is a tendency toward hypercoagulability in the postoperative period. This is manifested by changes in a number of coagulation parameters, and if not offset by some protective mechanism, thrombosis may occur. This protection appears to be mediated more through the fibrinolytic mechanism than through the action of antithrombin 3 (AT-3) because AT-3 activity diminishes in the early postoperative period. The introduction of variables such as invasion of the vascular system, intraoperative heparin administration, administration of whole blood, and insertion of a Dacron prosthesis does not appreciably affect the response of the coagulation profile to operative stress.


The relationship between endothelial dysfunction and oxidative stress in diabetes and prediabetes.
Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). The aim of the present study was to determine whether increased OS and impaired endothelial function, are present in early states of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Brachial artery flow-mediated dilatation (FMD) and nitrate-induced dilatation were measured in 133 subjects with carbohydrate abnormalities (45 IGT, 44 IFG and 44 Type 2 diabetes mellitus) and in 46 subjects with normal glucose tolerance (NGT). Waist circumference, body mass index, blood pressure and fasting lipid profiles were obtained, and glucose and insulin values in response to a 75-g oral glucose load were also measured. Plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity were determined. Patients with diabetes and prediabetes had a higher plasma MDA concentration, but a lower plasma SOD activity than the NGT group (p = 0.006) and SOD activity was positively associated with FMD (p = 0.039). FMD were significantly reduced in the groups of subjects with abnormal carbohydrate metabolism compared with the NGT group (p = 0.035). Among the subjects with diabetes and prediabetes, FMD showed a negative correlation with fasting glucose and/or plasma glucose level at 120 min after oral glucose tolerance test (p = 0.028). The results showed that endothelial dysfunction and increased OS were present in subjects with IGT and IFG, indicating endothelial damage in these stages.


Influence of heart rate and phase of the cardiac cycle on the occurrence of motion artifact in dual-source CT angiography of the coronary arteries.
Coronary CT angiography allows visualization of the coronary arteries. However, motion artifact can impair delineation of the coronary artery lumen and detection of coronary artery stenoses. We investigated the influence of heart rate and the segment of the cardiac cycle during which images are reconstructed on the occurrence of motion artifacts. We evaluated coronary CT angiography datasets obtained by 64-slice dual-source CT in 100 consecutive patients. Data were reconstructed at 13 time instants during the cardiac cycle and evaluated for the presence of motion artifact. Mean heart rate was 66±14 beats/min. Overall, 98 of 100 patients had evaluable datasets. For heart rates ≤60 beats/min, optimal image quality was uniformly found during late diastole (100% of cases with evaluable image quality during a time window between 65% and 75% of the cardiac cycle). With increasing heart rates, images reconstructed during late systole more frequently provided best image quality. However, image reconstruction could not be restricted to a systolic time period. To achieve evaluable image quality in 95% of cases, data acquired between 25% and 75% of the cardiac cycle had to be available for patients with heart rates >60 beats/min. Dual-source CT provides high image quality across a wide range of heart rates. Although data acquisition may be limited to diastole for patients with heart rates ≤60 beats/min, the availability of data acquired both during systole and diastole is necessary for patients with higher heart rates.


Repurposing antidepressants for anticancer drug discovery.
Drug repurposing is an attractive strategy for identifying new indications for existing drugs. Three approved antidepressants have advanced into clinical trials for cancer therapy. In particular, further medicinal chemistry efforts with tranylcypromine (TCP) have led to the discovery of several TCP-based histone lysine specific demethylase 1 (LSD1) inhibitors that display therapeutic promise for treating cancer in the clinic. Thus repurposing antidepressants could be a promising strategy for cancer treatment. In this review, we illustrate the anticancer mechanisms of action of antidepressants and also discuss the challenges and future directions of repurposing antidepressants for anticancer drug discovery, to provide an overview of approved antidepressant cancer therapies.


Incremental hemodialysis in pediatric patients.
Incremental hemodialysis follows the concept of adjusting dialysis dose according to residual kidney function. Data on incremental hemodialysis in pediatric patients is lacking. We conducted a retrospective analysis of children initiating hemodialysis between January 2015 and July 2020 in a single tertiary center, comparing the characteristics and outcomes of those who commenced with incremental hemodialysis vs with conventional thrice-weekly regimen. Data on forty patients, 15 (37.5%) on incremental hemodialysis and 25 (63%) on thrice-weekly hemodialysis were analyzed. No differences in age, estimated glomerular filtration rate and metabolic parameters were noted between groups at baseline, but there were more males (73 vs 40%, p = 0.04), more patients with congenital anomalies of kidney and urinary tract (60 vs 20%, p = 0.01), higher urine output (2.5 ± 1 vs 1 ± 0.8 ml/kg/h, p < 0.001), lower use of antihypertensive medications (20 vs 72%, p = 0.002) and lower prevalence of left ventricular hypertrophy (6.7 vs 32%, p = 0.003) in the incremental hemodialysis group vs thrice-weekly hemodialysis. During follow up, 5 (33%) incremental hemodialysis patients were transplanted, 1 (7%) remained on incremental hemodialysis at 24 months, and 9 (60%) transitioned to thrice-weekly hemodialysis at a median (IQR) time of 8.7 (4.2, 11.8) months. At last follow up, fewer patients who initiated incremental hemodialysis had left ventricular hypertrophy (0 vs 32%, p = 0.016) and urine output < 100 ml/24 h (20 vs 60%, p = 0.02) compared to thrice-weekly hemodialysis, with no significant differences in metabolic or growth parameters. Incremental hemodialysis is a viable option for initiating dialysis in selected pediatric patients, that may help improve patients' quality of life and reduce dialysis burden without compromising clinical outcome.


Carcinoembryonic antigen-immunoglobulin Fc fusion protein (CEA-Fc) for identification and activation of anti-CEA immunoglobulin-T-cell receptor-modified T cells, representative of a new class of Ig fusion proteins.
Chimeric immunoglobulin-T-cell receptor (IgTCR)-modified T cells ("designer T cells") kill tumor cells based on antibody-redirected recognition of tumor-associated antigen. Anti-carcinoembryonic antigen (CEA) designer T cells have been prepared and applied in adoptive cellular immunotherapy regimens for CEA-positive cancers. A CEA-immunoglobulin Fc (CEA-Fc) fusion protein was created from the A3B3 region of CEA and the Fc portion of human IgG for the purposes of activation and detection of anti-CEA designer T cells. CEA-Fc was expressed at high yield in CHO cells and purified to homogeneity in a single step on a protein A affinity column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that CEA-Fc formed disulfide-linked dimers with a molecular weight of about 170 kDa and a monomer size of 85kDa. The A3B3 CEA component of the CEA-Fc bound to anti-CEA monoclonal antibody MN-14, as well as to the single-chain Fv (sFv) derived from this antibody that was expressed in the IgTCR on the surface of designer T cells. The Fc portion of CEA-Fc was recognized by anti-human IgG Fc antibody and bound by human monocyte Fc receptors. CEA-Fc activated the anti-CEA designer T cells as plate-bound or monocyte-bound form but not as soluble form, as measured by CD69 expression and T-cell proliferation. Our results indicate that the CEA-Fc fusion protein can be used to detect the expression of the anti-CEA IgTCR chimeric receptors on the modified T cells, as well as to serve as an antigen to activate the anti-CEA IgTCR modified T cells. CEA-Fc is the prototype for a new class of antigen-Fc molecules that may significantly augment the analytic and therapeutic goals of adoptive designer T-cell immunotherapies.


Domestic abuse--an antenatal survey at King Edward VIII Hospital, Durban.
To determine exposure to domestic violence by a partner or spouse among pregnant women attending a public sector hospital in Durban, South Africa. Six hundred and four randomly chosen women from a low-income community were interviewed over a 6-month period using a standardised questionnaire. Thirty-eight per cent had experienced domestic violence at some point in their lives. Physical abuse (52%) was the most common, and 35% had been abused during the current pregnancy. Domestic violence is common in pregnancy among women attending a public sector hospital.


Silvaglins and related 2,3-secodammarane derivatives - unusual types of triterpenes from Aglaia silvestris.
Lipophilic crude extracts of leaves, stem and root bark of six different provenances of Aglaia silvestris were compared to determine species-specific chemical trends as well as infraspecific variability. 3,4-Secodammarane triterpenes formed the basic chemical equipment accompanied by the 2,3-seco derivative aglasilvinic acid, probably representing the precursor of the silvaglin A and isosilvaglin A characterised by a five membered ring A. In addition, the pregnane steroid pregnacetal was isolated and identified together with the known sesquiterpenes alpha-muurolene and viridiflorol, and the bisamide pyramidatin. Depending on the collection site all major triterpenes showed two different stereochemical trends either towards 20R or 20S configuration, giving rise to isolation and identification of the two isomers methylisofoveolate B (20S,24R) and methylfoveolate B (20R,24S) as well as the known derivatives shoreic acid (20S,24R), isoeichlerianic acid (20R,24S), and methylisoeichleriate (20R,24S). The structures were elucidated by 2D-NMR experiments and silvaglin A additionally by X-ray diffraction. The structural diversity and distribution of triterpenoids within the genus Aglaia is highlighted with respect to chemotaxonomic implications.


Structural features of diverse ligands influencing binding affinities to estrogen alpha and estrogen beta receptors. Part II. Molecular descriptors calculated from conformation of the ligands in the complex resulting from previous docking study.
A QSAR study is reported, in which the relationship between chemical structure of a set of compounds and the binding affinity to human estrogen receptor alpha and beta (ER-alpha and ER-beta) is modelled. Counterpropagation neural networks are used to predict experimental binding affinity of a range of substances. Several compounds as estrogenic chemicals, phytoestrogens, and natural and synthetic estrogens are treated with a structure-based approach that involves the protein structure. The conformations obtained with a docking methodology are used to calculate molecular descriptors. The models are built up with the neural network training procedure, which encodes the information present in molecular descriptors and related binding affinities of the pre-selected training set of compounds. In order to reach the best possible models, a selection of the descriptors using genetic algorithm was conducted. The selection was directed by the error in the prediction of binding affinities of compounds from the test set. The final models obtained for estrogen receptor alpha and beta were tested with an external validation set and were compared with the models obtained from a receptor-independent approach reported in the accompanying paper.


Determination of phenotypes of esterases (Set) in fresh saliva and saliva stains by disc electrophoresis and the distribution of Set phenotypes in the Japanese population.
A rapid and simple disc electrophoretic technique for the determination of saliva esterase (Set) types is described. The frequency of Set types was F 16.4%, FS 49.8% and S 33.8%. The estimated gene frequency of Set-1F was 0.413 and of Set-1S was 0.587. An accurate determination of Set types was possible in 5--7 week-old saliva stains. This system may be useful in medicolegal applications.


Antibody response to pneumolysin and to pneumococcal capsular polysaccharide in healthy individuals and Streptococcus pneumoniae infected patients.
Animal experiments have shown that antibodies against capsular polysaccharide enhance phagocytosis of pneumococcal bacteria and that antibodies against pneumolysin are anti-inflammatory and prevent pneumococcal invasion. It is not known if an antibody response to pneumolysin can be acquired from natural exposure to pneumococcal bacteria or how the concentration of pneumolysin antibody at the mucosal surface compares with that of antibodies against pneumococcal capsular polysaccharide. This study used an equal potency method to measure specific antibody concentrations against pneumolysin and pneumococcal capsular polysaccharides in order to facilitate comparative estimates of concentrations in saliva and serum. The results may provide experimental information as a basis for an improved pneumococcal vaccine strategy. Healthy individuals had higher IgM and IgG antibody concentrations against capsular polysaccharide than against pneumolysin in both saliva and serum, but for IgA the converse was true. Patients with acute pneumococcal infection had significantly lower concentrations of specific IgG antibodies against both antigens than the healthy group. These patients also had significantly higher concentrations of IgM antibody against both antigens than the healthy control group. Healthy individuals acquire a comparatively lower concentration of antibody to pneumolysin than to pneumococcal capsular polysaccharides from natural exposure to pneumococcal bacteria. Patients infected by pneumococcal bacteria have lower specific IgG antibody concentrations to both antigens than healthy individuals. These findings support the view that pneumolysin could potentially be used as a vaccine. For enhanced effectiveness, it could be used as a supplement to Pneumovax((R))II rather than as a replacement. The two acquired antibodies, i.e. to pneumolysin and to capsular polysaccharide, could then play their protective roles at different stages in the course of pneumococcal infection, and together contribute to an effective immune defence against Streptococcus pneumoniae.


Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.


Polarity-sensitive and lipid droplet-specific red emission fluorophore for identifying fatty liver of living mice through in vivo imaging.
The illustration of the correlation between lipid droplets (LDs) variation and nonalcoholic fatty liver disease (NAFLD) is a challenging and important work in biomedical research. Herein, a red emission fluorophore LD-HW containing donor-π-bridge-acceptor (D-π-A) structure was readily constructed and systematically investigated. It was found that LD-HW could selectively identify polarity variation accompanying with an obvious blue-shift (around 80 nm) in fluorescence spectra, and a sharp enhancement (about 440-fold) in fluorescence quantum yield (QY) over the solvent polarity ranging from water (polarity parameter Δf = 0.3200) to 1,4-dioxane (Δf = 0.0205). In addition, probe LD-HW could precisely light up LDs within a short time (≤5 min) through a wash-free procedure and real-time monitor the dynamic behavior of cellular LDs. More importantly, LD-HW exhibited an excellent performance in differentiating fatty liver through in vivo imaging the change of cellular LDs. The in situ fluorescence spectra of corresponding tissue section proved that polarity level in the liver of NAFLD mice was lower than that in normal mice. Taken together, probe LD-HW presented great potential in non-invasive diagnosis of fatty liver through in vivo imaging.


Inequity and benefit incidence analysis in healthcare use among Syrian refugees in Egypt.
The Syrian conflict has created the worst humanitarian refugee crisis of our time, with the largest number of people displaced. Many have sought refuge in Egypt, where they are provided with the same access to healthcare services as Egyptian citizens. Nevertheless, in addition to the existing shortcomings of the Egyptian health system, many obstacles specifically limit refugees' access to healthcare. This study looks to assess equity across levels of care after observing services utilization among the Syrian refugees, and look at the humanitarian dilemma when facing resource allocation and the protection of the most vulnerable. A cross-sectional survey was used and collected information related to access and utilization of outpatient and inpatient health services by Syrian refugees living in Egypt. We used concentration index (CI), horizontal inequity (HI) and benefit incidence analysis (BIA) to measure the inequity in the use of healthcare services and distribution of funding. We decomposed inequalities in utilization, using a linear approximation of a probit model to measure the contribution of need, non-need and consumption influential factors. We found pro-rich inequality and horizontal inequity in the probability of refugees' outpatient and inpatient health services utilization. Overall, poorer population groups have greater healthcare needs, while richer groups use the services more extensively. Decomposition analysis showed that the main contributor to inequality is socioeconomic status, with other elements such as large families, the presence of chronic disease and duration of asylum in Egypt further contributing to inequality. Benefit incidence analysis showed that the net benefit distribution of subsidies of UNHCR for outpatient and inpatient care is also pro-rich, after accounting for out-of-pocket expenditures. Our results show that without equitable subsidies, poor refugees cannot afford healthcare services. To tackle health inequities, UNHCR and organisations will need to adapt programmes to address the social determinants of health, through interventions within many sectors. Our findings contribute to assessments of different levels of accessibility to healthcare services and uncover related sources of inequities that require further attention and advocacy by policymakers.


Mechanical assessment of arterial dissection in health and disease: Advancements and challenges.
Arterial dissection involves a complex series of coupled biomechanical events. The past two decades have witnessed great advances in the understanding of the intrinsic mechanism for dissection initiation, and hence in the development of novel therapeutic strategies for surgical repair. This is due in part to the profound advancements in characterizing emerging behaviors of dissection using state-of-the-art tools in experimental and computational biomechanics. In addition, researchers have identified the important role of the microstructure in determining the tissue׳s fracture modality during dissection propagation. In this review article, we highlight a variety of approaches in terms of biomechanical measurements, computational modeling and histological/microstructural analysis used to characterize a dissection that propagates in healthy and diseased arteries. Notable findings with quantitative mechanical data are reviewed. We conclude by discussing some unsolved problems that are of interest for future research.


Promoting colorectal cancer screening discussion: a randomized controlled trial.
Provider recommendation is a predictor of colorectal cancer (CRC) screening. To compare the effects of two clinic-based interventions on patient-provider discussions about CRC screening. Two-group RCT with data collected at baseline and 1 week post-intervention. African-American patients that were non-adherent to CRC screening recommendations (n=693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Compared to the brochure group, greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p<0.001). Predictors of a discussion about CRC screening included computer group participation, younger age, reason for visit, being unmarried, colonoscopy self-efficacy, and family member/friend recommendation (all p-values <0.05). The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient-provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. This study is registered at www.clinicaltrials.gov NCT00672828.


Uterine artery Doppler at 11-14 weeks of gestation in chromosomally abnormal fetuses.
To determine whether the major chromosomal abnormalities are associated with impaired placentation in the first trimester of pregnancy. This was a prospective study of 692 singleton pregnancies undergoing fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried out and the mean pulsatility index was calculated just before chorionic villus sampling. The fetal karyotype was normal in 613 pregnancies and abnormal in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13, eight of Turner syndrome and 10 with other defects. There were no significant differences in the median value of uterine artery mean PI between any of the individual groups. Although in the combined group of trisomy 18, trisomy 13 and Turner syndrome fetuses, the median pulsatility index (1.60) was significantly higher than in the chromosomally normal group (median pulsatility index, 1.51; P = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index was below the 95th centile of the normal group (mean pulsatility index, 2.34). There was no significant association between uterine artery mean pulsatility index and fetal nuchal translucency thickness or fetal growth deficit. The high intrauterine lethality and fetal growth restriction associated with the major chromosomal abnormalities are unlikely to be the consequence of impaired placentation in the first trimester of pregnancy.


Trust deal offers higher salaries in lieu of pension.
An NHS trust has been criticised for offering nurses higher starting salaries if they opt out of the NHS pension.


Self-assembled mechanism of hydrophobic amino acids and β-cyclodextrin based on experimental and computational methods.
The β-cyclodextrin (β-CD) can be used to remove bitter taste of protein hydrolysates, which is attributed to its interaction with hydrophobic amino acids included within peptides. But the corresponding mechanism has not been fully clarified. Herein, we systematically investigate the interaction between β-CD and three hydrophobic amino acids involving tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe). We prove the formation of amino acid/β-CD supermolecular complexes determined by FS, UV, IR, DSC and NMR, manifesting that no new chemical bond is formed in these complexes. The theoretical interaction conformations are given by molecule docking and further supported by ONIOM (our Own N-layer Integrated Orbital molecular Mechanics) calculations, with the consideration of structural assignments, binding orientations, solvent effects, interaction energies and main forces to form these complexes. Molecular docking results suggest that the hydrophobic amino acids prefer to interact with β-CD by their aromatic ring, meaning hydrophobic interactions are main forces for them entering into the cavity of β-CD. ONIOM-based calculations provide a number of quantum-chemical parameters to confirm our experimental results; meanwhile, to demonstrate that H-bonds play an important role in maintaining the stability of three amino acid/β-CD complexes. This work is help for demonstrating the interaction mechanism of amino acid/β-CD supermolecular system, and guiding how to remove bitterness or undesirable taste of bioactive peptides, even other interested molecules.


Morphology of physiologically identified mitral cells in the carp olfactory bulb: a light microscopic study after intracellular staining with horseradish peroxidase.
Physiologically identified mitral cells in the carp olfactory bulb were stained by intracellular injection of horseradish peroxidase in order to study the morphology in detail. The somata were fusiform, elongated, oval, triangular, or irregular. The mean diameters of the somata were 30 microns X 14 microns. Two to five thick dendrites arose from the somata and frequently gave off branches to form glomerular tufts. The dendrites extended less than 400 microns; the dendritic field of single mitral cells in the medial or lateral part of the olfactory bulb was confined within the respective part of the bulb. The axons arose from either the somata or the dendrites and had a conical initial portion, usually with a smooth contour. Some cells had poorly developed intrabulbar axon collaterals. No difference between the mitral cells in the medial part of the olfactory bulb and those in the lateral part was found in the soma diameter, the dendritic diameter at the base, or the number of first-order dendrites. However, there was a difference in the site of the origin of the axon between them: most of the axons of the mitral cells in the medial part arose from the dendrites, while most of the axons of the mitral cells in the lateral part arose from the somata. The morphology of physiologically identified mitral cells is basically consistent with that reported in the Golgi studies of teleosts. The limited dendritic fields of mitral cells may underlie the previously reported functional separation of the olfactory bulb into medial and lateral parts. The results also indicate that the two parts of the teleost olfactory bulb are differentiated not only functionally but also morphologically.


Assessment of cognitive and interpersonal skills in clinical problem-solving--a comparison between certification examination and formative evaluation.
The study describes an analysis of the relationship between formative evaluation of performance in the residency program in Family Medicine and performance in the oral components of the Certification Examination. Implications for the process of certification of clinical competence are discussed.


Primary Total Hip Arthroplasty in Patients With Ehlers-Danlos Syndrome: A Retrospective Matched-Cohort Study.
Ehlers-Danlos syndromes (EDSs) are connective-tissue disorders resulting in joint laxity. Soft-tissue stability is a concern in these patients when they undergo total hip arthroplasty (THA). Our purpose was to compare THAs in the population with EDS with a matched control undergoing THA for osteoarthritis. Thirteen patients with EDS underwent THA from 1997 to 2017. Matching was 1:3 with a control group of patients who underwent THA for osteoarthritis. Matching was based on the gender, age, and length of follow-up. We found no difference in demographics or postoperative Harris Hip Scores between the cohorts (P > .05). Two patients (15.4%) with EDS and 2 patients (5.1%) in the control group suffered a dislocation. We found no difference in the reoperation or revision rate between the groups (P = .28). Patients with EDS have a significant improvement in postoperative Harris Hip Scores after THA. These patients also have a high dislocation rate after surgery, and alternative approaches and technologies such as dual-mobility components should be considered to reduce the rate of dislocation in this population.


A closer look at the synapse: dlg1[4K] enables cell-specific visualization of PSD-95/DLG1.
The PSD-95 homolog, DLG1, is important for excitatory synapse structure and function throughout the Drosophila nervous system. In this issue of Cell Reports Methods, Parisi et al. present a tool, dlg1[4K], that enables cell-specific DLG1 visualization without altering basal synaptic physiology. This tool will potentially enhance our understanding of neuronal development and function in both circuits and individual synapses.


Physical activity for obstructive sleep apnea after stroke? A pilot study assessing the contribution of body fluids.
Obstructive sleep apnea (OSA) and physical inactivity are common after stroke. Physical inactivity can lead to/or exacerbate edema following stroke, and the resultant overnight fluid shift may increase the risk of OSA. We aimed to investigate the effect of physical activity on nocturnal rostral fluid shift, sleep pattern, and edematous state of hemiparetic patients. Neck circumference (tape measured) and arms, legs, and trunk fluid volume (bioelectrical impedance spectrum analyzer) were measured before and after 2 polysomnography (PSG) examinations. In the lab, a whole night PSG was performed after the intervention. The intervention consisted of inactivity (lying down and sitting) or activity (standing, performing calf muscle contractions while standing, walking, and climbing stairs) between 13 and 21 h, after the randomization of the participants. With a 7-day interval, participants crossed over to the other group. From 126 eligible participants, 8 with hemiparetic post-first-ever ischemic stroke at the subacute phase were recruited (age: 53.2 ± 16.2; 6 women). Physical activity reduced AHI from 19 to 13 n°/h and wake after sleep onset from 76.5 to 60.3 min and increased fluid volume of paretic and non-paretic arms and trunk before sleep compared to inactivity. An acute bout of physical activity reduced OSA classification based on AHI (from moderate to mild) and sleep fragmentation. Our results provide preliminary evidence of a possible link between physical activity in patients after stroke as an intervention to counteract OSA severity and improve sleep.


Regulation of poly(ADP-ribose) polymerase mRNA levels during compensatory and mitogen-induced growth of rat liver.
Poly(ADP-ribose) polymerase mRNA levels were studied in hepatic regeneration following partial hepatectomy, and in hyperplasia induced by the mitogen lead nitrate. A significant increase in the level of poly(ADP-ribose) polymerase mRNA was found 8 h after partial hepatectomy when no detectable increase of DNA synthesis could be observed; the level of poly(ADP-ribose) polymerase transcripts increased up to six-fold within 1-2 days. A similar increase of the level of poly(ADP-ribose) polymerase mRNA was found 24 h after treatment with lead nitrate. A twofold increase in poly(ADP-ribose) polymerase activity was observed 2 days after (a) partial hepatectomy and (b) lead nitrate treatment. From these results an important role of poly(ADP-ribose) polymerase in cell proliferation could be suggested.


Effects of water temperature on growth performance, digestive enzymes activities, and serum indices of juvenile Coreius guichenoti.
This study was conducted to determine the optimal temperature for Juvenile Coreius guichenoti, which is critically endangered in China. Test fish with an initial body weight range of 17.60-18.78 g were reared in 5 independent recirculating aquaculture systems (RAS) with three tanks (50 fish/tank) for 8 weeks. The water temperature of the RAS was set at 14 °C, 18 °C, 22 °C, 26 °C, and 30 °C, respectively. At conclusion of the feeding trial, the effects of water temperature on C. guichenoti were analyzed based on survival, growth performance, digestive enzymes activities, and antioxidant capacity. The results showed that the fish survived in all temperature groups. The fish in the groups (26 °C and 30 °C) had higher values of body length, body weight, specific growth rate, weight gain rate, and daily gain than those in the group (22 °C). The lowest values of growth performance were observed in the groups (14 °C and 18 °C) among the 5 groups. The lowest values of feed conversion ratio (FCR) were observed in the group (26 °C). Regression analysis identified the minimum FCR at 26.55 °C. The feeding rates (FR) were increased gradually with the increase of temperature. Regression analysis identified the maximum FR at 28.33 °C. The activities of protease and lipase in the gut were higher than those in the liver, while amylase activity was lower in the gut than that in the liver. There were no significant differences in activities of protease and lipase among different parts of the intestinal tract at the temperatures range from 18 to 26 °C. When the temperature was out the optimal range, C. guichenoti would be under chronic stress, resulting in decreased lysozyme activity and cortisol concentration. Inconclusion, the optimal temperature for juvenile C. guichenoti is 26.55-28.33 °C based on the maximal growth performance and feed utilization.


Magnetron-based inline microwave fluid warmer.
To develop an in-line microwave fluid warming system that eliminates the difficulties of uneven heating that are characteristic of batch-mode microwave fluid warmers. Using a commercial microwave oven, we developed a method for warming fluid as it flowed through tubing along a defined path in the oven's cavity. Algorithms utilizing either proportional or adaptive control were used to control microwave heating cycles by varying the heating pulse-width during 3-second epochs. Methods of fluid entry and exit were devised to minimize microwave leakage. Heating performance was tested using icewater at multiple flow rates from 18 mL/min to 105 mL/min. In all warming tests, the system achieved temperature control without exceeding the maximum temperature allowable based on American Association of Blood Banks requirements. The adaptive control maintained the set temperature, with peak-to-peak oscillations of 2 degrees C or less. Microwave leakage was below the commercially required limit for home microwave appliances. The combination of proportional and adaptive control is successful in controlling the permanent magnet magnetron microwave energy to heat the icewater tested. The in-line microwave warmer has the potential to become a successful medical fluid warmer. More study is needed to determine the stability of the control system under clinical conditions, and to evaluate its utility for warming blood.


Systematic review of yoga for symptom management during conventional treatment of breast cancer patients.
Breast cancer is one of the most commonly diagnosed cancers in women in the US, and its treatments have significant physical and psychological side effects and long-term complications causing significant morbidity and decreased quality of life. Integrative medicine modalities, such as Yoga, have been found to reduce side effects of conventional treatments without interfering with the treatment itself and improve quality of life. In this systematic review, we specifically explored Yoga as a potential option for symptomatic management in patients undergoing conventional breast cancer treatments. We performed a literature search that was conducted to include the databases PubMed, PsychINFO, Cochrane Library, Scopus, and CINAHL, resulting in 28 randomized controlled trial (RCT) articles. We review the results of these trials regarding the impact of Yoga in this patient population. Overall, the majority of the RCT articles showed significant benefits of Yoga intervention in various aspects of quality of life, fatigue, nausea/vomiting, sleep quality, anxiety, depression, and distress. There are several studies that have explored the physiological mechanism behind the effects of Yoga and found that Yoga affects both the immune response and inflammation. These studies revealed that Yoga has a potential therapeutic role in the symptomatic management of breast cancer patients, enhancing quality of life during treatment as well as improving adherence to treatment. Future studies with more defined and consistent methodologies are necessary to fully understand the potential use of Yoga therapy in patients with breast cancer.


[Spontaneous neonatal arterial thrombosis: a report of 4 neonates].
Arterial thromboses are rare in newborns, mostly caused by arterial catheters. Neonatal arterial thrombosis occurring in other contexts is much rare. We report arterial thrombosis, not caused by catheterisation in 4 neonates hospitalised in the neonatology department of the Farhat Hached de Sousse hospital in Tunisia. The diagnosis of arterial thrombosis was made based on signs of ischemia in 2 patients affected by thrombosis of the iliac arteries. The symptoms were less clear: anuria associated with arterial high blood pressure in 1 patient affected by thrombosis of the abdominal aorta and by anuria with melena in a newborn with aortic and mesenteric thrombosis. Diagnosis was confirmed by Doppler sonography in 3 patients and based on autopsy data in 1 patient. A delay to consultation was noted in 3 patients, whose outcome was fatal. The progression was favourable after thrombolysis and anticoagulation using heparin in 1 patient with major aortic thrombosis. A review of the literature on the epidemiological, clinical, therapeutic and outcome data of the arterial thrombosis in the newborn child is provided.


Comparison of different modes of photo-activated disinfection against Porphyromonas gingivalis: An in vitro study.
Porphyromonas gingivalis (P. gingivalis), a Gram-negative periodontal pathogen, is frequently detected in subgingival plaques in patients with chronic periodontitis. Considering the insufficient results achieved by the current antimicrobial approaches, this study aimed to compare the susceptibility of P. gingivalis to the different modes of photo-activated disinfection in planktonic culture. Cultures of P. gingivalis were assigned into three main groups of photothermal disinfection with 810 nm laser in continuous mode + EmunDo® (indocyanine green based photosensitizer), 808 nm laser in pulse mode + Perio green® (indocyanine green based photosensitizer); and antibacterial photodynamic therapy with 662 nm laser + Radachlorin® photosensitizer. Then, the bacterial viability was determined by serial dilution method by counting the number of colonies forming units. The results were analyzed by one-way analysis of variance and Tukey test (p < 0.05). All three groups showed significant reduction in the viability of P. gingivalis (p < 0.001). However; this reduction was significantly higher in photothermal therapy with EmunDo®. Both methods of photodynamic and photothermal therapy were successful in Significant eradication of P. gingivalis. Although, photothermal approach was more efficient with EmunDo® in combination with 810 nm laser irradiation.


The drifting city: the role of affect and repair in the development of "Enabling Environments".
The city has become a defining feature of contemporary human experience, supporting diverse risk and enabling environments. Whilst urban risk environments have been the subject of numerous innovative research projects in recent years, the figure of the enabling environment is less well understood. This paper seeks to develop this figure through reference to recent scholarship in social theory, human geography and urban sociology. This figure will be illustrated throughout with data drawn from various qualitative research projects conducted in Melbourne, Australia and Vancouver, Canada. This qualitative research highlights the array of enabling characteristics present in urban drug use contexts, characteristics that have yet to be fully explored in relation to the development of innovative settings-based harm reduction strategies. This research draws attention to the ways particular urban settings support the development of affective and relational networks of "social repair" vital to the maintenance of health and wellbeing. These enabling characteristics serve to build social ties and enhance local networks; increase belonging and "connection to place"; and reinforce local "cultures of care". They also represent resources of enormous potential for harm reduction policy and practice. Greater attention to the array of assets and opportunities present in urban settings offers fresh insights into the nature of enabling environments and their role in reducing drug related harms and facilitating healthy growth and development.


Free sialic acid storage disease. A new Italian case.
Increased amounts of free sialic acid were found in cultured fibroblasts and urine of a 4-year-7-month-old Italian boy with mental retardation, hypotonia, failure to thrive, coarse facial features, convergent strabismus, pale skin and fair hair. Ultramicroscopic examination of conjunctival and skin tissues showed a number of membrane-bound vacuoles containing low-density granular material in the cytoplasm of the fibroblasts. The clinical, biochemical and ultrastructural findings are similar to those described in Salla disease. Neuraminidase activity is normal. The molecular basis of the sialic acid storage disease is not known. Evidence for defective transport of sialic acid across the lysosomal membrane has been demonstrated in the patient's fibroblasts. It is possible that this might represent the metabolic abnormality.


Development and characterization of wheat- Leymus racemosus translocation lines with resistance to Fusarium Head Blight.
Wheat scab (Fusarium Head Blight, FHB) is a destructive disease in the warm and humid wheat-growing areas of the world. Finding diverse sources of FHB resistance is critical for genetic diversity of resistance for wheat breeding programs. Leymus racemosus is a wild perennial relative of wheat and is highly resistant to FHB. Three wheat- L. racemosus disomic addition (DA) lines DA 5 Lr#1, DA 7 Lr#1 and DALr.7 resistant to FHB were used to develop wheat- L.racemosus translocation lines through irradiation and gametocidal gene-induced chromosome breakage. A total of nine wheat-alien translocation lines with wheat scab resistance were identified by chromosome C-banding, GISH, telosomic pairing and RFLP analyses. In line NAU 614, the long arm of 5 Lr#1 was translocated to wheat chromosome 6B. Four lines, NAU 601, NAU 615, NAU 617, and NAU 635, had a part of the short arm of 7 Lr#1 transferred to different wheat chromosomes. Four other lines, NAU 611, NAU 634, NAU 633, and NAU 618, contained translocations involving Leymus chromosome Lr.7 and different wheat chromosomes. The resistance level of the translocation lines with a single alien chromosome segment was higher than the susceptible wheat parent Chinese Spring but lower than the alien resistant parent L. racemosus. At least three resistance genes in L. racemosus were identified. One was located on chromosome Lr.7, and two could be assigned to the long arm of 5 Lr#1 and the short arm of 7 Lr#1.


Transcriptomic analyses reveal the pathways associated with the volatilization and resistance of mercury(II) in the fungus Lecythophora sp. DC-F1.
The biotic enzymatic reduction of mercury II [Hg(II)] to elemental Hg [Hg(0)] is an important pathway for Hg detoxification in natural ecosystems. However, the mechanisms of Hg(II) volatilization and resistance in fungi have not been understood completely. In the present study, we investigated the mechanisms of Hg(II) volatilization and resistance in the fungus Lecythophora sp. DC-F1. Hg(II) volatilization occurred during the investigation via the reduction of Hg(II) to Hg(0) in DC-F1. Comparative transcriptome analyses of DC-F1 revealed 3439 differentially expressed genes under 10 mg/L Hg(II) stress, among which 2770 were up-regulated and 669 were down-regulated. Functional enrichment analyses of genes and pathways further suggested that the Hg(II) resistance of DC-F1 is a multisystem collaborative process with three important transcriptional responses to Hg(II) stress: a mer-mediated Hg detoxification system, a thiol compound metabolism, and a cell reactive oxygen species stress response system. The phylogenetic analysis of merA protein homologs suggests that the Hg(II) reduction by merA is widely distributed in fungi. Overall, this study provides evidence for the reduction of Hg(II) to Hg(0) in fungi via the mer-mediated Hg detoxification system and offers a comprehensive explanation for its role within Hg biogeochemical cycling. These findings offer a strong theoretical basis for the application of fungi in the bioremediation of Hg-contaminated envionments.


Comparative analysis of calcium-binding protein-immunoreactive neuronal populations in the auditory and visual systems of the bottlenose dolphin (Tursiops truncatus) and the macaque monkey (Macaca fascicularis).
This study compares the distribution of three calcium-binding protein-immunoreactive (CaBP-immunoreactive) neuronal populations (calretinin-, calbindin- and parvalbumin-immunoreactive) in the visual and auditory systems in two mammalian species which are fundamentally different in their evolutionary traits and ecology, the aquatic toothed whale Tursiops truncatus (bottlenose dolphin) and the terrestrial Old World primate, Macaca fascicularis (long-tailed macaque). Immunocytochemical analyses, combined with computerized morphometry revealed that in the visual and auditory systems of the bottlenose dolphin, calretinin and calbindin are the prevalent calcium-binding proteins, whereas parvalbumin is present in very few neurons. The prevalence of calretinin and calbindin-immunoreactive neurons is especially obvious in the auditory system of this species. In both auditory and visual systems of the macaque monkey, the parvalbumin-immunoreactive neurons are present in comparable or higher densities than the calretinin and calbindin-immunoreactive neurons. In some structures of the visual and auditory systems of the macaque monkey, the calretinin- and calbindin-immunoreactive neurons are nearly absent. The prevalence of parvalbumin-immunoreactive over calretinin- and calbindin-immunoreactive neurons is particularly prominent in the visual system of primates. Thus, the dominant sensory systems in both aquatic and terrestrial mammals are enriched in specific phenotypes of calcium-binding protein-immunoreactive neurons.


Particle's mass may tip the scales to new physics.
New estimate of W boson mass conflicts with prediction from "standard model".


A basal troodontid from the Early Cretaceous of China.
Troodontid dinosaurs form one of the most avian-like dinosaur groups. Their phylogenetic position is hotly debated, and they have been allied with almost all principal coelurosaurian lineages. Here we report a basal troodontid dinosaur, Sinovenator changii gen. et sp. nov., from the lower Yixian Formation of China. This taxon has several features that are not found in more derived troodontids, but that occur in dromaeosaurids and avialans. The discovery of Sinovenator and the examination of character distributions along the maniraptoran lineage indicate that principal structural modifications toward avians were acquired in the early stages of maniraptoran evolution.


Vascular endothelial functions, carotid intima-media thickness, and soluble CD40 ligand levels in dipper and nondipper essential hypertensive patients.
The lack of nocturnal decline in blood pressure (BP) is associated with an increase in cardiovascular events. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. The purpose of this study was to examine the relationship between vascular endothelial functions, carotid intima-media thickness (cIMT), plasma sCD40L levels and circadian BP profile in patients with essential hypertension. The study population consisted of 81 essential hypertensive out-patients. BP dipping was defined as a night-to-day systolic and diastolic decrease >or=10%. Forty-seven dipper and 34 nondipper patients were compared. High sensitivity C-reactive protein (hs-CRP), sCD40L and urinary albumin were measured. Brachial artery flow-mediated dilatation (FMD) and cIMT was compared between the groups. sCD40L level (3.28 +/- 2.08 and 2.30 +/- 1.99 ng/ml, respectively, P = 0.036) and urinary albumin concentration (36.7 +/- 20.1 and 23 +/- 29.7 mg/l, respectively, P < 0.0001) were higher in nondippers than in dippers. Serum hs-CRP levels were not significantly different. FMD was found higher in dippers than nondippers (11.8 +/- 3.9% and 6.6 +/- 2.2%, respectively, P < 0.0001). The average cIMT was significantly higher in nondippers than dippers (0.928 +/- 0.060 Vs. 0.734 +/- 0.134 mm; P < 0.0001). Nondipper patern has an additional negative effect on endothelial functions in hypertensive patients. Nondippers have enhanced sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.


Forearm oxygen uptake during maximal forearm dynamic exercise.
This study was undertaken in an attempt to determine the maximal oxygen uptake in a small muscle group by measuring directly the oxygen expenditure of the forearm. Five healthy medical students volunteered. The subjects' maximal forearm work capacity was determined on a spring-loaded hand ergometer. Exercise was continued until exhaustion by pain or fatigue. Two weeks later intra-arterial and intravenous catheters were placed in the dominant arm. Blood samples for measurement of oxygen concentration were collected via the catheters. Forearm blood flow was measured by means of the indicator dilution technique. Oxygen uptake was determined according to the Fick principle. The forearm oxygen uptake attained at maximal work loads was a mean of 201 (SD +/- 56) mumol.min-1.100 ml-1. It was impossible at maximal exercise to discern a plateau of the oxygen uptake curve in relation to work output. It is suggested that a plateau in the oxygen uptake curve is not a useful criterion for maximal oxygen uptake in a small muscle group. Skeletal muscle may have an unused capacity for oxygen consumption even at maximal exercise intensity where muscle work cannot be continued due to muscle pain and fatigue.


Formation and control of nitrogenous DBPs from Western Australian source waters: Investigating the impacts of high nitrogen and bromide concentrations.
We studied the formation of four nitrogenous DBPs (N-DBPs) classes (haloacetonitriles, halonitromethanes, haloacetamides, and N-nitrosamines), as well as trihalomethanes and total organic halogen (TOX), after chlorination or chloramination of source waters. We also evaluated the relative and additive toxicity of N-DBPs and water treatment options for minimisation of N-DBPs. The formation of halonitromethanes, haloacetamides, and N-nitrosamines was higher after chloramination and positively correlated with dissolved organic nitrogen or total nitrogen. N-DBPs were major contributors to the toxicity of both chlorinated and chloraminated waters. The strong correlation between bromide concentration and the overall calculated DBP additive toxicity for both chlorinated and chloraminated source waters demonstrated that formation of brominated haloacetonitriles was the main contributor to toxicity. Ozone-biological activated carbon treatment was not effective in removing N-DBP precursors. The occurrence and formation of N-DBPs should be investigated on a case-by-case basis, especially where advanced water treatment processes are being considered to minimise their formation in drinking waters, and where chloramination is used for final disinfection.


Inflow Angle Impacts Morphology, Hemodynamics, and Inflammation of Side-wall Intracranial Aneurysms.
Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. Prospective. A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs = 0.31), WSSavg-IA (rs = -0.45), and AWE grades (rs = 0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P = 0.901), Vavg-IA (P = 0.699), Vmax-IA (P = 0.482), Flowavg-IA (P = 0.550), Flowmax-IA (P = 0.689), WSSavg-IA (P = 0.573), and AWE grades (P = 0.872). A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. 3 TECHNICAL EFFICACY: Stage 2.


Thyroid storm following rapid sequence intubation.
Thyroid storm is a rare complication with an estimated incidence ranging from 0.61 to 0.76 cases per 100,000 people. Common causes include intrinsic hyperthyroidism, such as in Grave's disease, infection, surgery, severe emotional stress, and acute trauma to the thyroid gland. Without immediate treatment, mortality is seen in up to 30% of cases. Here, we report a case of a 46-year-old male who presented with a possible food impaction for the past 48 h. The patient developed extreme hypertension, tachycardia, and diaphoresis immediately following rapid sequence intubation (RSI), which, after further work-up, was due to thyroid storm.


Adverse effects of brompheniramine on pulmonary function in a subset of asthmatic children.
The role of antihistamines in the therapy of bronchial asthma has remained controversial. Early studies suggested a possible aggravation of symptoms but more recent studies implied their safety. Ten asthmatic children who reported a feeling of chest tightness and subsequent wheezing after taking a preparation containing brompheniramine maleate were studied in addition to 10 control asthmatic children who reported no such adverse effect. All children were only intermittently symptomatic and did not require constant bronchodilator therapy. They were well at the time of the study. Challenges were performed with the antihistamine alone (4 mg of brompheniramine maleate), a decongestant-antihistamine combination (4 mg of brompheniramine maleate, 5 mg of phenylephrine HCl, 5 mg of phenylpropanolamine HCl), and a placebo. Results indicated a statistically significant decrease in pulmonary function in the study children when challenged with the antihistamine and decongestant-antihistamine preparation but not when challenged with the placebo. The 10 control asthmatic children did not exhibit this phenomenon and premedication with theophylline prevented the decrease in pulmonary function in the study group. Therefore a subset of asthmatic children does appear to exist in whom the use of an antihistamine may be harmful.


Linking the Phyllosphere Microbiome to Plant Health.
The phyllosphere harbors diverse microbial communities that influence ecosystem functioning. Emerging evidence suggests that plants impaired in genetic networks harbor an altered microbiome and develop dysbiosis in the phyllosphere, which pinpoints plant genetics as a key driver of the phyllosphere microbiome assembly and links the phyllosphere microbiome to plant health.


Plant growth promoting endophyte promotes cadmium accumulation in Solanum nigrum L. by regulating plant homeostasis.
The homeostasis regulating mechanism of endophyte enhancing cadmium (Cd) extraction by hyperaccumulator is poorly understood. Here, an endophyte strain E3 that belonged to Pseudomonas was screened from Cd hyperaccumulator Solanum nigrum L., which significantly improved the Cd phytoextraction efficiency of S. nigrum by 40.26%. The content and translocation factor of nutrient elements indicated that endophyte might regulate Cd accumulation by affecting the uptake and transport of magnesium and iron in S. nigrum. Gene transcriptional expression profile further revealed that SnMGT, SnIRT1, and SnIRT2, etc., were the key genes involved in the regulation of S. nigrum elements uptake by endophyte. However, changes in elemental homeostasis did not negatively affect plant growth. Endophyte inoculation promoted plant growth by fortifying photosynthesis as well as recruiting specific bacteria in S. nigrum endosphere, e.g., Pseudonocardiaceae, Halomonas. Notably, PICRUSt2 analysis and biochemical characterization jointly suggested that endophyte regulated starch degradation in S. nigrum leaves to maintain photosynthetic balance. Our results demonstrated that microecological characteristics of hyperaccumulator could be reshaped by endophyte, also the homeostasis regulation in endophyte enhanced hyperaccumulator Cd phytoextraction was significant.


Ectasia of the basilar artery: the breadth of the clinical spectrum and the diagnostic value of computed tomography.
Five angiographically confirmed cases of ectasia of the basilar artery are described. Three patients presented with the classical combination of lower cranial nerve, bulbar, cerebellar and long tract signs and dementia, one as obstructive hydrocephalus with papilloedema, and the fifth with symptoms of chiasmal compression. All were above middle age and hypertensive. CT scanning demonstrated a partially calcified, tubular, enhancing prepontine and suprasellar mass in every case. Ventricular enlargement and cerebral parenchymal abnormalities were also present. These appearances are sufficiently characteristic to make invasive radiological investigation unnecessary.


Urinary excretion of acrylonitrile and its metabolites in rats.
Quantitative analysis of the dose-dependent urinary excretion of acrylonitrile and its metabolites was carried out in male Wistar rats following inhalation exposure of the animals to 1, 5, 10, 50 and 100 ppm acrylonitrile for 8 h. Quantitative analysis of acrylonitrile in urine was performed by gas chromatography. The urinary metabolites cyanoethyl mercapturic acid, S-carboxymethyl cysteine and hydroxyethyl mercapturic acid were measured by a modified amino acid analysis, and thiodiglycolic acid by GC-MS. The excretion pattern of the compound and its metabolites was dependent on the exposure level; it is concluded that urinary determination of the unmetabolized acrylonitrile and two of its metabolites, cyanoethyl mercapturic acid and thioglycolic acid, may be useful for biological monitoring of industrial exposure.


Investigation of molecular size of transcription factor TFIIE in solution.
Human general transcription factor IIE (TFIIE), a component of a transcription preinitiation complex associated with RNA polymerase II, was characterized by size-exclusion chromatography, mass spectrometry, analytical ultracentrifugation, and small-angle X-ray scattering (SAXS). Recombinant human TFIIE was purified to homogeneity and shown to contain equimolar amounts of TFIIEalpha (50 kDa) and TFIIEbeta (35 kDa) by SDS-PAGE. In the analysis of size-exclusion chromatography of the purified sample, as already reported, TFIIE was shown to be a 170-kDa alpha(2)beta(2) heterotetramer. However, by using electrospray ionization mass spectrometry the purified sample gave the molecular mass of 84,152 +/- 5, indicating that TFIIE is an alphabeta heterodimer but not a heterotetramer. Analytical ultracentrifugation experiment of TFIIE provided that only a single component with the molecular mass of ca. 80,000 existed in solution, also suggesting an alphabeta heterodimer. In addition, its extraordinarily rod-like molecular shape was confirmed by SAXS. It is likely that the rod-like molecular shape of TFIIE has misled larger molecular size in size-exclusion chromatography, which was calibrated by globular proteins. It is demonstrated that TFIIE exists as a heterodimer under our present conditions in solution, although two molecules of heterodimer might be required for the formation of the preinitiation complex with RNA polymerase II for starting the transcription process.


Global Burden of Prostate Cancer and Association with Socioeconomic Status, 1990-2019: A Systematic Analysis from the Global Burden of Disease Study.
Both the morbidity and mortality of prostate cancer are increasing worldwide. Updated evaluations of prostate cancer burden and its global, regional and national patterns are essential for formulating effective preventive strategies. To investigate prostate cancer incidence, mortality, and disability-adjusted life years (DALYs) between 1990 and 2019 to facilitate preventive measures and control planning. Annual incident cases, deaths, DALYs, age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs rates (ASDRs) of prostate cancer between 1990 and 2019 were derived from the Global Burden of Diseases study 2019. Percentage changes in incident cases, deaths and DALYs and estimated annual percentage changes (EAPCs) in ASIRs, ASMRs and ASDRs were calculated to quantify temporal trends. Correlations between EAPCs and socio-demographic index (SDI) and universal health coverage index (UHCI) were evaluated by Pearson correlation analyses. Globally, the number of incident cases, deaths, and DALYs of prostate cancer increased by 116.11%, 108.94%, and 98.25% from 1990 to 2019, respectively. The ASIR increased by an average of 0.26% (95% CI: 0.14%, 0.37%) per year between 1990 and 2019, while the ASMR and ASDR decreased by an average of - 0.75% (95% CI: - 0.84%, - 0.67%) and - 0.71% (95% CI: - 0.78%, - 0.63%) per year in this period, respectively. Epidemic trends in the burdens of prostate cancer were not uniform throughout different groups of SDI or geography. The burdens of prostate cancer varied across SDI regions, with an increasing trend in ASIR, ASMR, and ASDR in low and low-middle SDI regions between 1990 and 2019. A significant positive correlation between the EAPC in ASIR and UHCI was observed in countries with a UHCI < 70 (ρ = 0.37, p < 0.001). Prostate cancer remains a major global health burden due to the increase in incident cases, deaths, and DALYs in the past three decades. These increases are likely to continue as the population ages, which indicates a potential talent gap in the trained healthcare workforce. The diversity of prostate cancer development models implies the importance of specific local strategies tailored for each country's risk factor profile. Prevention, early detection and more effective treatment strategies for prostate cancer are essential.


Macrophage function in the acute phase of lactic dehydrogenase virus-infection of mice: suppression of superoxide anion production in normal mouse peritoneal macrophages by interferon-alpha in vitro.
The effect of interferon (IFN)-alpha on the release of superoxide anions (O2-) by normal mouse macrophages (PEM) was examined. Sera from LDV-infected mice at 1 day, but not at 7 days post-infection, suppressed the O2- release by PEM. When PEM were exposed in vitro for 24 h to IFN-alpha, their capacity to release O2- was significantly suppressed. Progressive suppression of O2- release with increasing IFN-alpha concentration was observed. These results suggest that IFN-alpha in the circulation may be one of several suppressive factors on macrophage function in the early phase of infection and IFN-alpha may play a modulatory role in inflammation and immunity.


The application of microfluidic devices for viral diagnosis in developing countries.
Whilst diseases such as diabetes and cardiovascular disorders are increasing in the developed world, the main threat to global health remains viral-based infectious disease. Such diseases are notably prevalent in developing countries, where they represent a major cause of mortality; however, their detection and prevention is typically hampered by poor infrastructure and a lack of resources to support the sophisticated diagnostic tools commonly found in modern laboratories. Microfluidic-based diagnostics has the potential to close the gap between developed and developing world medical needs due to the robustness and reduced operating costs such technology offers. The most recent developments in microfluidic diagnostics for viral infections have explored the separation and enumeration of immune cells, the capture and identification of viral particles, and antiviral drug evaluation within microchannels and chambers. Advances in solid-phase separation, isothermal amplification, real-time detection of nucleotide products, and improved efficiency of detection systems in microfluidic platforms have also opened up opportunities for diagnostic innovation. This chapter reviews the potential capability microfluidic technology can offer in addressing the practical challenges of providing diagnostic technology for developing countries, illustrated by research on key viral diseases.


Mg2+ homeostasis and avoidance of metal toxicity.
Because Mg2+ is required for a wide variety of cellular functions, its intracellular levels must be tightly regulated. In the Gram-negative bacterium Salmonella enterica, three transporters mediate Mg2+ uptake: the P-type ATPases MgtA and MgtB, whose expression is transcriptionally induced in low Mg2+ by the Mg2+-regulated PhoP/PhoQ two-component system; and CorA, whose transcription is regulated neither by the levels of Mg2+ nor by the PhoP/PhoQ system. We now report that mutants defective in phoP or in both mgtA and mgtB are hypersensitive to oxidative stress-dependent Fe (II)-mediated killing. These mutants display increased iron accumulation and heightened Ni2+ uptake. Inactivation of the corA gene restored Fe(II) resistance to the phoP mutant and eliminated uptake of Ni2+. Neither corA transcription nor CorA protein levels were altered in the phoP mutant, suggesting that CorA alters its activity in response to the presence of PhoP-regulated determinants. Downregulation of CorA activity in low Mg2+ environments may enable Salmonella to avoid the uncontrolled influx of toxic metals.


Incidental epidermolytic hyperkeratosis and focal acantholytic dyskeratosis in common acquired melanocytic nevi and atypical melanocytic lesions.
Epidermolytic hyperkeratosis (EH) and focal acantholytic dyskeratosis (FAD) are distinct histologic patterns that have been observed incidentally in a variety of benign and malignant skin lesions, including melanocytic lesions. Our motivation for this study was to determine whether FAD and/or EH was significantly associated with atypical melanocytic lesions. Skin biopsy specimens of melanocytic lesions diagnosed at our facility over a 3-month period were examined for the occurrence of FAD and EH. Whereas both FAD and EH are uncommon findings, FAD was statistically increased in atypical melanocytic lesions (P =.0172). EH was not found to differ significantly in common acquired melanocytic nevi vs atypical melanocytic lesions. Although both can be found in association with nonneoplastic skin diseases, as well as cutaneous neoplasms, FAD, but not EH, might serve as a marker for melanocytic atypia. Taken together with findings in the literature, FAD might serve as marker for atypical cutaneous proliferations as a whole.


Public speaking training in front of a supportive audience in Virtual Reality improves performance in real-life.
Public speaking is a challenging task that requires practice. Virtual Reality allows to present realistic public speaking scenarios in this regard, however, the role of the virtual audience during practice remains unknown. In the present study, 73 participants completed a Virtual Reality practice session while audience was manipulated to be supportive or unsupportive or presentations were practiced without audience. Importantly, following the virtual practice, participants held the presentation during a real university course via Zoom. We measured emotional experience, self-efficacy, and the subjective evaluation of performance at baseline, after VR practice, and after the real presentation. Additionally, participants' performance in the real presentation was evaluated by instructors (blinded to condition). Supportive in contrast to unsupportive audiences led to more positive believes about one's own performance, while there were no changes in beliefs in the group without audience. Importantly, practice in front of a supportive compared to unsupportive audience resulted in a more positive evaluation of speaker confidence in real-life public speaking as rated by the instructors. These results demonstrate an impact of virtual social feedback during public speaking on subsequent subjective performance evaluation. This may increase self-confidence resulting in actual improved public speaking performance in real-life.


Thoron levels in the dwellings of Hyderabad city, Andhra Pradesh, India.
Thoron and its progeny concentration levels were measured in the urban Hyderabad area using solid state nuclear track detector (SSNTD) based dosimeters. Measurements were carried out on quarterly cycles making four measurements at each location in a calendar year. More than 100 dwellings of different construction types were chosen for the study across Hyderabad city. The thoron concentration levels were found to vary between 8 and 330 Bq m(-3). The geometric mean value of thoron concentration was found to be 37.3 Bq m(-3) (GSD = 2.3) with an average of 55 +/- 57 Bq m(-3). Results were analysed for different category of houses with respect to their construction type. It was found that the dwellings with mud flooring had higher thoron levels.


Thoracic deformity and hiatal hernia (intrathoracic stomach) in the elderly.
The incidence of hiatal hernia (HH) increases with age. Vertebral fracture, kyphosis, and pulmonary emphysema are suspected as possible causes. We aimed to analyze the relationship between thoracic deformities and HH in the elderly, using a deformity index. The study participants comprised 427 inpatients at a long-term-care hospital for the elderly in Japan. The Haller index (HI) was calculated on the transverse thoracic computerized tomography images according to the following formula: transverse diameter of the thorax/anterior-posterior diameter of the thorax. HH was diagnosed when an intrathoracic stomach was seen on the computed tomography images. The average HI calculated for all cases and for women--but not for men--decreased with increasing age. HH was diagnosed in 21 patients (4.9%). The incidence of HH in women was higher than in men (male vs. female = 2.0% vs. 7.4%). The mean value of HI in the HH patients (1.651 ± 0.251) was significantly lower than that in non-HH patients (2.345 ± 0.460). Enlargement of the anterior-posterior diameter of the thorax occurs in the elderly and is associated with the occurrence of HH.


Horace wells' demonstration of nitrous oxide in Boston.
Horace Wells, a dentist in Hartford, Connecticut, first used nitrous oxide in dentistry in December 1844. A few weeks later he travelled to Boston, Massachusetts, to demonstrate to physicians and dentists the use of nitrous oxide in painful procedures. Wells' unsuccessful demonstration of nitrous oxide for the extraction of a tooth is well known, but other details of this trip are poorly understood. A description of Wells' visit to Boston was compiled using information from 21 statements and 5 newspaper notices. The precise date and location of Wells' demonstration could not be determined. There is no primary evidence that Wells' demonstration occurred in the surgical amphitheater (Ether Dome) at Massachusetts General Hospital. Wells' demonstration of nitrous oxide probably occurred around the end of January 1845, in a public hall on Washington Street, Boston.


Unbiased selection of bone marrow derived cells as carriers for cancer gene therapy.
There is currently great interest in development of cell-based carriers for delivery of viral vectors to metastatic tumors. To date, several cell carriers have been tested based largely upon their predicted tumor-localizing properties. However, cell types may exist which can be mobilized from the circulation by a tumor which have not yet been identified. Here we use an unbiased screen of bone marrow (BM) cells to identify cells which localize to tumors and which might serve as effective candidate cell carriers without any prior prediction or selection. Unsorted BM cells from green fluorescent protein (GFP)-transgenic donor mice were adoptively transferred into C57Bl/6 mice bearing pre-established subcutaneous B16 melanoma tumors. Forty-eight hours and eight days later, tumors, organs and blood were analyzed for GFP-expressing cells by flow cytometry. The phenotype of GFP cells in organs was determined by co-staining with specific cell surface markers. CD45(+) hematopoietic cells were readily detected in tumor, spleen, bone marrow, blood and lung at both time points. Within these CD45(+) cell populations, preferential accumulation in the tumor was observed of cells expressing Sca-1, c-kit, NK1.1, Thy1.2, CD14, Mac-3 and/or CD11c. Lymphodepletion increased homing to spleen and bone marrow, but not to tumors. We have used an in vivo screen to identify populations of BM-derived donor cells which accumulate within tumors. These studies will direct rational selection of specific cell types which can be tested in standardized assays of cell carrier efficiency for the treatment of metastatic tumors.


Pharmacists as patient advocates: A series of case studies illustrating the impacts of a regular pharmacist service in residential aged care (nursing homes).
Medicine-related problems are common in older people living in residential aged care facilities (RACFs). Recognising the significant medicine-related problems, the Australian government has announced a $345 million funding package to employ on-site pharmacists in RACFs starting in 2023. The new on-site pharmacists are to provide a range of clinical services to reduce medicine-related adverse events, promote quality use of medicines, and improve clinical governance and education. Underpinning these services, the authors argue that pharmacists play the critical role as resident advocates. This study aims to demonstrate how pharmacists can enhance their advocacy responsibility within and beyond the clinical environment to not only reduce medicine-related adverse events but also improve residents' overall health and quality of life. This study uses a case series methodology to demonstrate pharmacists' diverse roles in advocating for residents and their families. The case studies were based on participants enrolled in the Reducing Medicine-Induced Deterioration and Adverse Reactions (ReMInDAR) trial, a randomised controlled trial testing the effects of a regular pharmacist service across the Australian RACFs. Pharmacists' advocacy ranged from persistence in follow-up with a resident's general practitioner (GP) to ensure the GP was aware that a patient was experiencing bleeding and bruising while on an anticoagulant, to advocating for a new bed for a resident with peripheral oedema who had been sleeping in his chair due to fear of falling out of his current bed. Our trial focussed on pharmacists serving as the residents' advocate to improve their overall health and quality of life, rather than just addressing a list of medicine-related problems. The pharmacist model used in the ReMInDAR trial supports pharmacists to work to their full scope of practice, helps guide the Australian government's new on-site pharmacist program, and serves as an exemplar pharmacist in aged care model internationally.


Cost-effective tannery wastewater treatment using cyanobacteria: insights on the growth pattern and seedling vigor improvement with spent biomass.
Nowadays to cope-up with the emerging global clean-water crisis, wastewater needs to be remediated properly to be used as an alternative source. Here a cost-effective approach has been taken to treat heavily-polluted (BOD-1234.33 mg L-1, COD-1706.64 mg L-1, TDS-6984 mg L-1, and sulfide-140.8 mg L-1 ammonium-134.5 mg L-1) Tannery Waste Water (TWW). Three cyanobacteria were (Arthrospira platensis, Leptolyngbyavalderiana, and Anabaenasphaerica) used as bio-reagents in pilot-scale treatment. Wastewater remediation-potential and biomass-generation capacity were evaluated in various TWW concentrations. The maximum biomass growth and the highest pollution removal percentage was observed when exposed to 50% TWW; although among the tested strain, Arthrospira and Leptolyngbya performed better than Anabaena by showing greater pollution removal potential (BOD 93%, COD 94%, sulfide 99%, ammonium 93%) in one hand and higher biomass production rate (100 mg L-1 Day-1) on the other. DO was increased noticeably by 10-15-fold. Morphological characterizations of tannery wastewater exposed Anabaena revealed unusual thick sheath formation, along with heterocyst and akinete formation in their trichome. Biochemical characterizations of remediating cyanobacteria showed presence of wastewater-accumulated nutrients (N, P, K). Nutrient-loaded biomass improved growth of rice and chickpea seedlings when used as a growth promoter. These facts have been illustrated by factor analysis and discriminant analysis. Cyanobacteria-mediated pilot-scale tannery wastewater treatment would create ecologically and economically-sustainable technology for clean-water production. The online version contains supplementary material available at 10.1007/s13205-023-03712-x.