Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.
Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA. Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels. Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine. The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.


Wettability of denture relining materials under water storage over time.
Poor wettability of denture relining materials may lead to retention problems and patient discomfort. Purpose of this study is to compare and evaluate wettability of nine denture relining materials using contact angle measurements under air and water storage over time. Nine denture relining materials were investigated in this study. Two heat-curing polymethyl-methacrylate (PMMA) denture base materials: Vertex RS, Lang, one self-curing polyethyl-methacrylate (PEMA) chairside reline resin: Rebase II, six silicone relining materials: Mucopren soft, Mucosoft, Mollosil® plus, Sofreliner Touch, GC Reline™ Ultrasoft, Silagum automix comfort were used in this experiment. Contact angles were measured using high-resolution drop shape analysis system (DSA 10-MK2, KRUESS, Germany) under three conditions (in air after setting, 1 hour water storage, and 24 hours water storage). Nine materials were classified into three groups according to material composition (Group 1: PMMA, Group 2: PEMA, Group 3: Silicone). Mean values of contact angles were compared using independent samples t-test and one-way ANOVA, followed by a Scheffe's post hoc analysis (α= 0.01). CONTACT ANGLES OF MATERIALS TESTED AFTER AIR AND WATER STORAGE INCREASED IN THE FOLLOWING ORDER: Group 1 (PMMA), Group 2 (PEMA), Group 3 (Silicone). Heat-cured acrylic denture base resins had more wettability than silicone relining materials. Lang had the highest wettability after 24 hours of water storage. Silicone relining materials had lower wettability due to their hydrophobicity. Wettability of all denture relining materials, except Rebase II and Mollosil® plus, increased after 24 hours of water storage. Conventional heat-cured resin showed the highest wettability, therefore, it can be suggested that heat-cured acrylic resin is material of choice for denture relining materials.


The Role of Microorganisms and Carbon-to-Nitrogen Ratios for Microbial Protein Production from Bioethanol.
With industrial agriculture increasingly challenging our ecological limits, alternative food production routes such as microbial protein (MP) production are receiving renewed interest. Among the multiple substrates so far evaluated for MP production, renewable bioethanol (EtOH) is still underexplored. Therefore, the present study investigated the cultivation of five microorganisms (2 bacteria, 3 yeasts) under carbon (C), nitrogen (N), and dual C-N-limiting conditions (molar C/N ratios of 5, 60, and 20, respectively) to evaluate the production (specific growth rate, protein and biomass yield, production cost) as well as the nutritional characteristics (protein and carbohydrate content, amino acid [AA] profile) of MP production from bioethanol. Under C-limiting conditions, all the selected microorganisms showed a favorable AA profile for human nutrition (average AA score of 1.5 or higher), with a negative correlation between protein content and growth rate. Maximal biomass yields were achieved under conditions where no extracellular acetate was produced. Cyberlindnera saturnus and Wickerhamomyces anomalus displayed remarkably high biomass yields (0.40 to 0.82 g cell dry weight [CDW]/g EtOHconsumed), which was reflected in the lowest estimated biomass production costs when cultivated with a C/N ratio of 20. Finally, when the production cost was evaluated on a protein basis, Corynebacterium glutamicum grown under C-limiting conditions showed the most promising economic outlook. IMPORTANCE The global protein demand is rapidly increasing at rates that cannot be sustained, with projections showing 78% increased global protein needs by 2050 (361 compared to 202 million tonprotein/year in 2017). In the absence of dedicated mitigation strategies, the environmental effects of our current food production system (relying on agriculture) are expected to surpass the planetary boundaries-the safe operating space for humanity-by 2050. Here, we illustrate the potential of bioethanol-renewable ethanol produced from side streams-as a main resource for the production of microbial protein, a radically different food production strategy in comparison to traditional agriculture, with the potential to be more sustainable. This study unravels the kinetic, productive, and nutritional potential for microbial protein production from bioethanol using the bacteria Methylorubrum extorquens and Corynebacterium glutamicum and the yeasts Wickerhamomyces anomalus, Cyberlindnera saturnus, and Metschnikowia pulcherrima, setting the scene for microbial protein production from renewable ethanol.


[Down-regulation of TRIP6 expression induces actin cytoskeleton rearrangements in human carcinoma cell lines].
Structure and dynamics of actin cytoskeleton play a role ih regulation of cell adhesion, spreading and migration. TRIP6 is a LIM domain-containing protein interacting with many actin-associated proteins and in addition modulating activity of certain transcription factors. To study functions of TRIP6 we inhibited its expression in A549 and A431 cells by short interfering RNAs (siRNAs). The TRIP6 knock-down lead to the increased number and length of stress fibers and to the induction of locomotive phenotype. There was observed decreased number and reorganization of focal adhesions revealed by staining for paxillin, and loss of cell to cell adhesions revealed by staining for E-cadherin. The above changes in cell morphology were accompanied by 2-fold increase in the cell motility rate assessed by the wound healing assay. Thus, down-regulation of TRIP6 in the cell lines used results in increase in the features characteristic to malignant transformation of epithelial cells. Possible mechanisms for the observed effects are discussed.


Loudness constancy for noise and speech: How instructions and source information affect loudness of distant sounds.
The physical properties of a sound evolve when traveling away from its source. As an example, the sound pressure level at the listener's ears will vary according to their respective distance and azimuth. However, several studies have reported loudness to remain constant when varying the distance between the source and the listener. This loudness constancy has been reported to occur when the listener focused attention on the sound as emitted by the source (namely the distal stimulus). Instead, the listener can focus on the sound as reaching the ears (namely the proximal stimulus). The instructions given to the listener when assessing loudness can drive focus toward the proximal or distal stimulus. However, focusing on the distal stimulus requires to have sufficient information about the sound source, which could be provided by either the environment or by the stimulus itself. The present study gathers three experiments designed to assess loudness when driving listeners' focus toward the proximal or distal stimuli. Listeners were provided with different quality and quantity of information about the source depending on the environment (visible or hidden sources, free field or reverberant rooms) and on the stimulus itself (noise or speech). The results show that listeners reported constant loudness when asked to focus on the distal stimulus only, provided enough information about the source was available. These results highlight that loudness relies on the way the listener focuses on the stimuli and emphasize the importance of the instructions that are given in loudness studies.


Inhibitory effect of TNF-alpha on the intestinal absorption of galactose.
Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-alpha seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-alpha on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-alpha decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF-alpha inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved.


Quality-Based Procedures for Knee Replacement, Hip Replacement, and Hip Fracture: Physiotherapists' Perceptions of Adherence, Barriers, and Facilitators.
Purpose: This mixed-methods study examined the perceived barriers to and facilitators of implementing best-practice guidelines (BPGs) and adhering to provincial Quality-Based Procedures (QBPs) by Ontario physiotherapists working with patients after total knee replacement (TKR), total hip replacement (THR), and hip fracture (HF). Method: Using snowball sampling, 93 hospital and home care physiotherapists working with patients after TKR, THR, or HF completed a Web-based survey. A subset of these participated in follow-up semi-structured telephone interviews. Results: The perception of QBP adherence varied, with self-reported adherence rates across identified practice standards for TKR, THR, and HF reported as 62%, 69%, and 60%, respectively. Physiotherapists generally believed that BPGs improved outcomes; however, they identified clinical experience as their primary guide to practice. Only 66% perceived that their institutions met provincial standards. Barriers to BPG implementation and QBP adherence included insufficient time, lack of access to QBPs, and limited awareness of current BPGs. Qualitative themes included awareness and knowledge, flexibility and funding, communication, and availability of and equitable access to outpatient and community-based physiotherapy services. Conclusions: Physiotherapists reported that they primarily used clinical experience to inform care after TKR, THR, and HF, but they were also supportive of BPGs and QBPs. The results suggest that increased access to and education about QBPs, as well as supportive resources, could increase their integration into clinical practice.


COSTS AND BENEFITS OF PLANT RESPONSES TO DISEASE: RESISTANCE AND TOLERANCE.
A major assumption of models of the evolution of plant resistance to disease is that plant resistance involves fitness costs. To test this assumption, a field experiment was performed so that a quantitative-genetic analysis could be used to detect fitness costs to Ipomoea purpurea of resistance to different fungal isolates of Colletotrichum dematium, a pathogenic fungus causing the disease anthracnose. This experiment yielded no evidence that resistance to anthracnose involves direct fitness costs. Nevertheless, trade-offs in plant fitness that were unrelated to resistance were detected between different disease environments. Tolerance, defined as the ability to compensate in part for fitness decrements caused by disease, was found to involve fitness costs. Halfsib families that were more tolerant of disease had lower fitness in the absence of disease. The possibility that the cost of tolerance could obscure fitness costs of resistance is explored.


Phytochemical, pharmacological and ethnobotanical studies of Rhazya stricta Decne.
Rhazya stricta Decne. is an important medicinal species that is rich in alkaloids containing anticancer alkaloids also. This paper reviews phytochemical, pharmacological and ethnobotanical studies of R. stricta. Phytochemical and pharmacological aspects of the species have been thoroughly explored. Over 100 alkaloids have been isolated from R. stricta, but the pharmacological activities are known for only a few of these compounds. Very few ethnobotanical studies of R. stricta have been done, and there is a particular need for such studies in various regions of South Asia and in Middle Eastern countries where the species grows. These ethnobotanical studies should investigate herbal recipes of R. stricta and their use for curing diseases. The genetic diversity, chemotaxonomy and allelopathy of R. stricta have not yet been explored, and these studies are recommended, with the ultimate goal of benefiting local communities in regions where R. stricta grows. This should be achieved by sharing knowledge and through the manufacture of herbal drugs from R. stricta's active chemical constituents, while protecting intellectual property rights and following the World Health Organization's guidelines for safety and efficacy.


Cymantrene radical cation family: spectral and structural characterization of the half-sandwich analogues of ferrocenium ion.
The anodic one-electron oxidation of three members of the half-sandwich family of piano-stool compounds MnCp (gamma)(CO) 3, where Cp (gamma) is a generic cyclopentadienyl ligand, has been studied in a CH 2Cl 2/[NBu 4][TFAB] electrolyte (TFAB = [B(C6F5) 4] (-)). The long-sought 17 e (-) radical cation of the parent complex MnCp(CO) 3 (cymantrene, 1, E 1/2 = 0.92 V vs ferrocene) has been shown to be persistent in solutions that use weakly coordinating anions in place of more nucleophilic traditional electrolyte anions. Spectroscopically characterized for the first time, 1 (+) was shown to absorb in the visible (530 nm), near-IR (2066 nm), and IR (2118, 1934 cm (-1)) regions. It was ESR-active at low temperatures (g parallel = 2.213, g perpendicular = 2.079, A parallel (Mn) = 79.2 G, A perpendicular (Mn) = 50 G) and NMR active at room temperature (delta = 22.4 vs TMS). The radical cations of the Cp-functionalized analogues, Mn(eta (5)-C5H 4NH2)(CO) 3, 2, E 1/2 = 0.62 V, and MnCp*(CO) 3 (Cp*= eta (5)-C 5Me 5, 3), E 1/2 = 0.64 V, were generated electrochemically as well by the chemical oxidant [ReCp(CO) 3] (+). The structures of 2 (+) and 3 (+) were determined by X-ray crystallographic studies of their TFAB salts. Compared to the structures of the corresponding neutral compounds, the cations showed elongated Mn-C(O) bonds and shortened C-O bonds, displaying the effect of diminished metal-to-CO backbonding. The bond-length changes in the Mn(CO) 3 moiety were much larger in 3 (+) (avg changes, Mn-C(O) = + 0.142 A, C-O = -0.063 A) than in 2 (+) (avg changes, Mn-C(O) = + 0.006 A, C-O = -0.003 A). Although there were only minor changes in the metal-to-center ring distances upon oxidation of either 2 or 3, there was decidedly less bending of the C(N) atom out of the cyclopentadienyl plane in 2 (+) compared to 2. The optical, vibrational, and magnetic resonance spectra of radicals 2 (+) and 3 (+) were also observed. The spectral data argue for the SOMOs of the 17-electron species being largely located on the Mn(CO) 3 moiety, having 40-50% Mn d-orbital character, with the ground states of the radicals, most likely (2)A'', lying close in energy (within about 6000 cm (-1)) to excited states that are responsible for their rapid electronic relaxations. The cymantrenyl moiety is proposed as an anodic redox tag (or label) having physical and chemical properties that are significantly different from those of its ferrocenyl analogue.


Sorting out the evidence on natriuretic peptides.
B-type natriuretic peptide (BNP) is a cardiac neurohormone released as pre-proBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP have been used to identify patients with heart failure (HF). Clinical considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, interpretation of their units of measure, and the rapid availability of the test results. The BNP assay is currently used as a diagnostic and prognostic aid in HF and as a prognostic marker in acute coronary syndromes (ACS). In general, a BNP level less than 100 pg/mL excludes acutely decompensated HF. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in HF, related to HF severity, predictive of sudden death, and prognostic for death in ACS. This article will sort out the literature concerning the use of these peptides in a variety of clinical scenarios.


Disseminated Mycobacterium avium infection in a cat.
A domestic shorthair cat was presented for lethargy and ataxia. Clinical findings included an abdominal mass, lumbosacral pain, ataxia. Aspirates from the liver and lymph nodes revealed intracellular, negative-staining rods. Treatment for presumptive mycobacterium infection was unsuccessful and the cat was euthanized. Disseminated Mycobacterium avium was confirmed on culture.


Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro.
We report a case of a surgical site infection caused by clindamycin-susceptible, erythromycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) that did not respond to treatment with clindamycin. The MRSA isolate obtained after treatment was resistant to clindamycin but was found to be identical by pulsed-field gel electrophoresis to the clindamycin-susceptible isolate obtained before treatment. A post hoc erythromycin-induction test (D test) confirmed the presence of in vitro inducible macrolide-lincosamide-streptogramin B resistance (iMLS) in the pretreatment isolate. Erythromycin induction testing confirmed in vitro iMLS in 90 (56%) of 161 erythromycin-resistant, clindamycin-susceptible clinical S. aureus isolates overall and in a significantly higher proportion (78%) of methicillin-susceptible S. aureus isolates from pediatric patients. Our clinical laboratory currently tests all S. aureus isolates for iMLS before reporting clindamycin susceptibility.


College athletics, body size, and cancer mortality.
Data are presented on mortality from neoplasms as determined from death certificates in a cohort of 8393 college men, according to athletic status in college. Major athletes (lettermen) died significantly more often from neoplasms than nonathletes. Mean age at death from neoplasms (underlying cause) was significantly lower in major athletes than in both minor athletes and nonathletes. After matching major athletes with nonathletes of comparable body size (height and weight), differences in proportional mortality and mean age at death from neoplasms persisted, although not statistically significant for the smaller samples. Correlation coefficients (Pearson r) and partial r's between weight in college and age at death from neoplasms were negative but of low magnitude. Some possible explanations for the differences between major athletes and nonathletes are discussed.


Data mining and machine learning approaches for prediction modelling of schistosomiasis disease vectors: Epidemic disease prediction modelling.
This research presents viable solutions for prediction modelling of schistosomiasis disease based on vector density. Novel training models proposed in this work aim to address various aspects of interest in the artificial intelligence applications domain. Topics discussed include data imputation, semi-supervised labelling and synthetic instance simulation when using sparse training data. Innovative semi-supervised ensemble learning paradigms are proposed focusing on labelling threshold selection and stringency of classification confidence levels. A regression-correlation combination (RCC) data imputation method is also introduced for handling of partially complete training data. Results presented in this work show data imputation precision improvement over benchmark value replacement using proposed RCC on 70% of test cases. Proposed novel incremental transductive models such as ITSVM have provided interesting findings based on threshold constraints outperforming standard SVM application on 21% of test cases and can be applied with alternative environment-based epidemic disease domains. The proposed incremental transductive ensemble approach model enables the combination of complimentary algorithms to provide labelling for unlabelled vector density instances. Liberal (LTA) and strict training approaches provided varied results with LTA outperforming Stacking ensemble on 29.1% of test cases. Proposed novel synthetic minority over-sampling technique (SMOTE) equilibrium approach has yielded subtle classification performance increases which can be further interrogated to assess classification performance and efficiency relationships with synthetic instance generation.


Tolbutamide inhibits gastrin release in man.
Tolbutamide significantly decreased fasting plasma gastrin after 5 min of intravenous infusion in patients with atrophic gastritis, duodenal ulcer, or insulin-dependent diabetes mellitus (IDDM) as well as in healthy volunteers. Increased plasma insulin and decreased blood glucose were observed in patients with atrophic gastritis, duodenal ulcer and healthy volunteers, but not in patients with IDDM. Suppression of plasma gastrin in healthy volunteers was also observed following oral administration of tolbutamide. Despite the observed decrease in plasma gastrin, neither basal nor tetragastrin-stimulated acid output was changed for 30 min following tolbutamide infusion in healthy volunteers. Thus, our data suggest that tolbutamide inhibits gastrin release in man via mechanisms independent of changes in plasma insulin, blood glucose or acid secretion.


Integrated analysis of leaf morphological and color traits in different populations of Chinese cabbage (Brassica rapa ssp. pekinensis).
QTLs and candidate gene markers associated with leaf morphological and color traits were identified in two immortalized populations of Brassica rapa, which will provide genetic information for marker-assisted breeding. Brassica rapa is an important leafy vegetable consumed worldwide and morphology is a key character for its breeding. To enhance genetic control, quantitative trait loci (QTLs) for leaf color and plant architecture were identified using two immortalized populations with replications of 2 and 4 years. Overall, 158 and 80 QTLs associated with 23 and 14 traits were detected in the DH and RIL populations, respectively. Among them, 23 common robust-QTLs belonging to 12 traits were detected in common loci over the replications. Through comparative analysis, five crucifer genetic blocks corresponding to morphology trait (R, J&U, F and E) and color trait (F, E) were identified in three major linkage groups (A2, A3 and A7). These might be key conserved genomic regions involved with the respective traits. Through synteny analysis with Arabidopsis, 64 candidate genes involved in chlorophyll biosynthesis, cell proliferation and elongation were co-localized within QTL intervals. Among them, SCO3, ABI3, FLU, HCF153, HEMB1, CAB3 were mapped within QTLs for leaf color; and CYCD3;1, CYCB2;4, AN3, ULT1 and ANT were co-localized in QTL regions for leaf size. These robust QTLs and their candidate genes provide useful information for further research into leaf architecture with crop breeding.


Prevention of surgical site infection and sepsis in pregnant obese women.
Obesity is a major determinant of health outcomes and is on the increase in women worldwide. It predisposes to surgical site infection (SSI). Risk factors for the SSI include extremes of age, smoking, comorbidities such as hypertension and diabetes, inappropriate vertical abdominal and or uterine wall incisions, increased operating time, subcutaneous layer of 3 cm or more, and unnecessary use of subcutaneous drain. Most bacteria that cause SSIs are human commensals. Common organisms responsible for SSI include Staphylococcus aureus and coliforms such as Proteus mirabilis, and Escherichia coli. A surgeon's gloves post caesarean section in the obese has a preponderance of Firmicutes and Bacteroidetes, which increases SSI risk. The interaction of skin commensals and vaginal microbiome at the surgical incision site increases the risk of SSI in the obese compared to non-obese. Minimizing the risk of SSI involves modification of risk factors, timely treatment of SSI to prevent sepsis and compliance with the recommended care bundles.


Influence of ultrasonic frequency on Swan band sonoluminescence and sonochemical activity in aqueous tert-butyl alcohol solutions.
The multibubble sonoluminescence (MBSL) spectra of t-BuOH aqueous solutions submitted to power ultrasound at 20, 204, 362, and 613 kHz show emissions for the Δυ = -1 to Δυ = +2 vibrational sequences of C2* Swan system (d(3)Πg → a(3)Πu). The Δυ=+2 emission overlaps with the CH(A-X) emission band. The maximal Swan band emission is observed when the MBSL of water itself is almost completely quenched. In general, MBSL is more intense at high-frequency compared to 20 kHz ultrasound. However, in the presence of Xe, the MBSL of C2* at 20 kHz is so bright that it can be seen by the unaided eye as a blue glow in the close vicinity of the ultrasonic tip. The intensity of the C2* band emission exhibits a maximum vs t-BuOH concentration: 0.1-0.2 M at 20 kHz and (1-8) × 10(-3) M at high-frequency ultrasound. Such a huge difference is attributed to a much smaller bubble size at high ultrasonic frequency or, in other words, to a much higher bubble surface/volume ratio providing more efficient saturation of the bubble interior with t-BuOH vapors and to the fact that high frequency bubbles remain active for many more cycles than 20 kHz ones, thus accumulating more hydrocarbon decomposition products. Simulation of the emission spectra using Specair software demonstrated the absence of thermal equilibrium for C2* radicals (Tv > Tr), where Tv and Tr are the vibrational and the rotational temperature, respectively. In Ar, Tv decreases with increasing t-BuOH concentration reaching a steady value in the concentration domain that corresponds to C2* emission maximum intensity. In the presence of Xe an extremely high Tv is obtained, which is explained by the relatively low ionization potential of Xe providing a higher electron temperature of nonequilibrium plasma generated during bubble collapse. Analysis of the gaseous products of t-BuOH sonolysis reveals a significant sonochemical activity even at high t-BuOH concentration when MBSL is totally quenched, indicating that drastic conditions could be produced also within nonsonoluminescing cavitation bubbles.


Superoxide (O2-) assay monocyte adherence test for the detection of cell-mediated immunity in cancer patients.
The reactivity of mononuclear cells from patients with breast cancer to the 3 M KCl extract of breast tumor was tested using the superoxide (O2-) assay monocyte adherence test. The mononuclear cells were incubated with the 3 M KCl extract of breast tumor or normal breast tissues in a microcell for spectrophotometer analysis. After 2 h incubation, the nonadherent cells were removed, and the O2- generated from the monocytes adherent to the intersurface of the microcell was assayed. Thirty of 36 patients with breast cancer before treatment reacted to the extract of breast tumor. Sixteen patients showed adherence inhibition and 14 adherence stimulation. None of 8 patients with breast cancer reacted to the extract of lung tumor. Of 31 control donors (19 healthy volunteers and 12 patients with cancer of other organs), only 3 reacted to the extract of breast tumor.


Electrochemical impedance spectroscopy for black lipid membranes fused with channel protein supported on solid-state nanopore.
Black lipid membranes (BLMs) have been used for detecting single-channel activities of pore-forming peptides and ion channels. However, the short lifetimes and poor mechanical stability of suspended bilayers limit their applications in high throughput electrophysiological experiments. In this work, we present a synthetic solid-state nanopore functionalized with BLM fused with channel protein. A nanopore with diameter of ~180 nm was electrochemically fabricated in a thin silicon membrane. Folding and painting techniques were demonstrated for production of stable suspended BLMs followed by incorporation of transmembrane protein, ENaC. Membrane formation was confirmed by employing electrochemical impedance spectroscopy (EIS) in the frequency regime of 10-2-105 Hz. Results show that electrochemically fabricated solid state nanopore support resulted in excellent membrane stability, with >1 GΩ of up to 72 and 41 h for painting and folding techniques, respectively. After fusion of ENaC channel protein, the BLM exhibits the stability of ~5 h. We anticipate that such a solid-state nanopore with diameter in the range of 150-200 nm and thickness <1 µm could be a potential platform to enhance the throughput of ion-channel characterization using BLMs.


The three important traits for cooking and eating quality of rice grains are controlled by a single locus in an elite rice hybrid, Shanyou 63.
The cooking and eating quality of the rice grain is one of the most serious problems in many rice-producing areas of the world. In this study, we conducted a molecular marker-based genetic analysis of three traits, amylose content (AC), gel consistency (GC) and gelatinization temperature (GT), that are the most important constituents of the cooking and eating quality of rice grains. The materials used in the analysis included F(2) seeds, an F(2:3) population, and an F(9) recombinant inbred-line population from a cross between the parents of 'Shanyou 63', the most widely grown hybrid in rice production in China. Segregation analyses of these three generations showed that each of the three traits was controlled by a single Mendelian locus. Molecular marker-based QTL (quantitative trait locus) analyses, both by one-way analysis of variance using single marker genotypes and by whole-genome scanning with MAPMAKER/QTL, revealed a single locus that controls the expression of all three traits. This locus coincided with the Wx region on the short arm of chromosome 6, indicating that all three traits were either controlled by the Wx locus or by a genomic region tightly linked to this locus. This finding has provided clues to resolving the molecular bases of GC and GT in future studies. The results also have direct implications for the quality improvement of rice varieties.


Three-dimensional superlattice engineering with block copolymer epitaxy.
Three-dimensional (3D) structures at the nanometer length scale play a crucial role in modern devices, but their fabrication using traditional top-down approaches is complex and expensive. Analogous to atomic lattices, block copolymers (BCPs) spontaneously form a rich variety of 3D nanostructures and have the potential to substantially simplify 3D nanofabrication. Here, we show that the 3D superlattice formed by BCP micelles can be controlled by lithographically defined 2D templates matching a crystallographic plane in the 3D superlattice. Using scanning transmission electron microscopy tomography, we demonstrate precise control over the lattice symmetry and orientation. Excellent ordering and substrate registration can be achieved, propagating through 284-nanometer-thick films. BCP epitaxy also showed exceptional lattice tunability, with a continuous Bain transformation from a body-centered cubic to a face-centered cubic lattice. Lattice stability was mediated by molecular packing frustration, and surface-induced lattice reconstruction was observed, leading to the formation of a unique honeycomb lattice.


Surface smoothness effect for the direct growth of carbon nanotubes on bulk FeCrAl metal substrates.
We investigate effects of surface smoothness and surface chemistry on the nature of multi-walled CNTs (MWCNTs) grown directly on FeCrAl substrates. A single sample was grown that contained a gradation in surface morphologies ranging from 2.9 nm to 30.2 nm RMS. The MWCNTs were grown using ethylene and H2 gases. Characterization was done using atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger elemental surface analysis. In smooth regions, MWCNTs demonstrated high-density vertical aligned growths; however, patches of approximately 10-20 microm where poor MWCNT growth occurred. In contrast, rough regions of the surface exhibited a continuous blanket layer of MWCNTs, albeit growth was spaghetti-like throughout this layer. The variation in nature of MWCNT growths was directly dependent on the surface roughness, which can affect surface growth chemistry of MWCNTs. Auger elemental analysis determined carbon was observed everywhere on the surface, but carbon was strongest over the smooth regions of high density growth; while relatively less carbon was detected over the patches with poor MWCNT growth, as well as over the blanket layer of the rough region. Oxygen was also measured, which was detected both within the patches of poor MWCNT growth in the smooth regions and over the blanket layer of the rough region. However, measurements of Cr and Al were exhibiting mixed trends: Cr was detected more strongly than Al over the rough region; whereas the opposite was observed in the patches of poor MWCNT growth in the smooth region. The surface smoothness affects the surface chemistry involving the nature of MWCNT growth and may also affect the surface chemistry involving the metal substrate itself; therefore, comparisons on the nature of MWCNT growths must also take careful consideration of the surface smoothness.


KML001 and doxercalciferol induce synergistic antileukemic effect in acute lymphoid leukemia cells.
KML001 (NaAsO2, sodium metaarsenite, KOMINOX), a kind of arsenic compound, that has shown promising efficacy in non-Hodgkin's lymphoma (NHL) both in vitro and in vivo. In our study, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. The results showed that KML001 inhibited cell proliferation in two types of ALL cell lines, CCRF-CEM and Molt-4. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells. In addition, we also tested the possibility of synergy of KML001 with doxercalciferol, a vitamin D2 derivative. Also, we found that a combination of KML001 with doxercalciferol showed a synergistic effect on ALL cell lines and this could be due to its different mechanism of action. Overall, our findings demonstrated KML001 could be a promising antileukemic agent especially when it is combined with doxercalciferol in ALL treatment.


Subclassification of the presynaptic alpha 2-autoreceptors in rabbit brain cortex.
1. alpha 2-Adrenoceptor binding sites have been subclassified into alpha 2A sites of which a main characteristic is very low affinity for prazosin, and alpha 2B sites with relatively high affinity for prazosin. The presynaptic alpha 2-autoreceptors in rabbit brain cortex were studied in order to classify them in terms of alpha 2A and alpha 2B. Release of [3H]-noradrenaline in cortical slices was elicited by trains of 4 pulses delivered at 100 Hz. 2. Clonidine caused concentration-dependent inhibition of the stimulation-evoked overflow of tritium, with an EC50 of 7.5 nM and a maximal inhibition by 96%. 3. The following alpha-adrenoceptor antagonists shifted the concentration-response curve of clonidine to the right (antagonist-receptor dissociation constants KD in brackets): yohimbine (14 nM), 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazo le (BRL 44408; 15 nM) and 1,2-dimethyl-2,3,9,13betetrahydro-1H-dibenzo[c,f]imidazo[1,5-a]aze pine (BRL 41992; 630 nM). Prazosin 1 microM and 2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)-isoquinolinedione (AR-C 239) 1 microM failed to antagonize the effect of clonidine. Higher concentrations of prazosin and AR-C 239 greatly accelerated the basal efflux of tritium. 4. The method used permits the functional determination of antagonist affinities undistorted by endogenous alpha 2-autoinhibition. A comparison with affinities derived from radioligand binding experiments indicates that the presynaptic alpha 2-autoreceptors in rabbit brain cortex are markedly different from the alpha 2B-subtype and probably belong to the prazosin-insensitive alpha 2A-subtype.


A Breastfeed-Promoting Mobile App Intervention: Usability and Usefulness Study.
Breastfeeding is proven to have lasting health benefits for both mothers and infants; however, 6-month exclusive breastfeeding rate remains below 20% in Thailand. Although the number of research literature and commercial apps for breastfeeding women is significantly growing, they are country-specific and restricted to English-speaking users. There exists a major knowledge gap on how mobile health apps could support breastfeeding in Thailand. To address these gaps, MoomMae has been developed with the intention to support Thai women in breastfeeding outside of their homes and in keeping their feeding records. The aim of this study was to evaluate the usability and usefulness of MoomMae, a mobile phone app designed to support breastfeeding women. Our study was reviewed and approved by Thailand's National Science and Technology Development Agency (NSTDA) ethics committee. A total of 21 breastfeeding women with at least one Android phone or tablet were recruited via convenience and snowball sampling. The study process for each participant was as follows: the participant was requested to attend a preuse interview and given the app to use for 4 weeks. Following this period, a postuse interview was conducted to examine the usability and usefulness of the app. Both sessions were held individually and audiorecorded for qualitative analysis. The mean scores of usability and usefulness from the postuse survey were 4.33 (SD 0.87; range 1-5) and 4.60 (SD 0.74; range 2-5). Our qualitative analysis revealed a total of 137 feedbacks: 71 related to usability and 66 associated with usefulness. A further sentimental analysis showed that comments on usability were generally negative (59 negative, 11 positive, and 1 neutral), and comments on usefulness were relatively positive (56 positive, 9 negative, and 1 neutral). We discovered 26 unique design issues and proposed recommendations for future improvement. Our usability and usefulness assessment of MoomMae demonstrated that MoomMae has a great potential to be a useful self-management tool for breastfeeding mothers in Thailand. The qualitative analysis suggested that the app is supportive of breastfeeding on demand, but the flow and inputs of the app should be redesigned to be more intuitive. For future implementations, the most desirable feature is a pump-reminding notification system.


[The role of lectins from probiotic microorganisms in sustaining the macroorganism].
The notion of lectins has been expanded with special reference to lectins of probiotic microorganisms (LPM). New data on LPM and their properties are considered in the context of a new concept of systemic organization of LPM being developed. Conditions for complete separation of poly (N-acetylgalactosamine-?)-binding lectins and polyMan-?/oligomannoside/mannan-binding lectins are developed on the assumption that they contain a single carbohydrate-binding site in their structure. It is shown that strain typing of probiotic microorganisms is possible based not only on protein but also on LPM composition. The observed peculiarities of LPM functioning substantially extend the concept of informational superiority of integral interatomic networks over their isolated components. This approach makes it possible to set functioning of LPM systems against that of lectin systems of other components of human microbiota as prevailing in the support of the normal status of the macrorganism. The results demonsatrate the unique character of LPM systems and suggest good prospects for their application in medicine, biotechnology and nanotechnology.


Resource depletion potentials from bottom-up models: Population dynamics and the Hubbert peak theory.
Life cycle impact assessment uses so-called characterization factors to address different types of environmental impact (e.g. climate change, particulate matter, land use…). For the topic of resource depletion, a series of proposals was based on heuristic and formal arguments, but without the use of expert-based models from relevant research areas. A recent study in using fish population models has confirmed the original proposal for characterization factors for biotic resources of the nineties. Here we trace the milestones of the arguments and the designs of resource depletion, delivering an ecological-based foundation for the biotic case, and extend it by a novel analysis of the Hubbert peak theory for the abiotic case. We show that the original abiotic depletion potential, used for two decades in life cycle assessment, estimates accurately a marginal depletion characterization factor obtained from a dynamic model of the available reserve. This is illustrated for 29 metal resources using published data.


Histochemical changes of the developing human cerebral neocortex. Studies on two enzymes of energy metabolism in three cortical areas.
Developmental changes of two mitochondrial enzymes, succinate- and menadione-dependent alpha-glycerophosphate dehydrogenases (SDH, M alpha GPDH) have been studied by histochemical techniques in early autopsy material in the following areas of human neocortex: area 4 (motor cortex), area 17 (visual cortex) and area 40 (associative cortex). Each area studied revealed a special enzymatic architecture. SDH - a marker of oxidative activity - develops for several years after birth and in some areas (4 and 40) reaches its adult pattern only after 11 years. Considerable modifications occur during development in the relative activities of the different cortical layers. SDH activity initially appears in layers which send projections to subcortical relays or receive specific thalamocortical afferents. Layers which receive cortico-cortical projections mature later on. In contrast to SDH activity that of M alpha GPDH is elevated already before birth, increases until one month of age and decreases afterwards. This enzyme present in neuroblasts disappears from mature cortical neurons, except from those of the VIth layer. The distribution of this enzyme in cortical layers of the child is opposite to that of SDH. The developmental evolution of these two enzymes has been confirmed by biochemical assays.


Comparison of 2 iron doses in infants receiving recombinant human erythropoietin therapy.
To compare iron sufficiency in premature infants receiving high-dose recombinant human erythropoietin (r-HuEPO), 1200 IU/kg per week, supplemented with 6 or 12 mg/kg per day of enteral iron. We conducted a prospective, double-blind, controlled study of premature infants receiving r-HuEPO therapy, randomly assigned to receive 2 different doses of iron. Measurements of ferritin, iron, total iron-binding capacity, reticulocyte count, hemoglobin level, and hematocrit were obtained at baseline, 4, and 6 weeks. Transferrin saturation was calculated; the number of blood transfusions and the incidences of sepsis were recorded. This study was performed in the neonatal intensive care unit at Loma Linda University Children's Hospital, Loma Linda, Calif. Infants with a gestational age of 32 weeks or younger, older than 7 days, and receiving r-HuEPO therapy from March 1, 1997, to June 30, 1998, were eligible for the study. Infants were randomly assigned to receive 6 mg/kg per day or 12 mg/kg per day of enteral iron during a course of r-HuEPO therapy for 4 to 6 weeks. Sixty-four infants were enrolled in the study. Twelve infants did not complete the study; 52 completed 4 weeks and 41 completed 6 weeks of the study. While ferritin levels and transferrin saturation decreased in both groups over the study period, there were no differences between the 2 study groups. Infants receiving high-dose r-HuEPO therapy (1200 IU/kg per week) decrease their ferritin levels (measure of iron stores) even when receiving high enteral iron supplementation. Given that the ferritin levels were similar between the 2 groups, we speculate that the additional iron either was not absorbed or was not stored.


A Systematic Review and Meta-Analysis on Comparative Kinematics in the Lumbopelvic Region in the Patients Suffering from Spinal Pain.
Lumbopelvic kinematics has been observed to include different parameters and directly relate to the movement of the hip spine. In the current scenario, more than 65 million people have been suffering from spinal pain, and 18% of adults experience chronic spinal pain. This systematic review and meta-analysis selected 9 studies for analysis via electronic databases like EMBASE, MEDLINE, Web of Science, Scopus, CINAHL, and Cochrane (CENTRAL). After collecting the data, the dataset has been systematically analyzed through statistical methodologies using RevMan and Stata. Out of 116 studies initially scrutinized, nine were finally selected for the meta-analysis. When range of motion was studied via meta-analysis, it was noted that a considerable reduced movement was noted in the lumbar region of the spine when people were suffering from lower back pain in comparison to control group people. Hence, reduced lumbar range of motion, no difference in the angle of lordosis, and no significant difference in extension and rotation in people with lower back pain were found. However, variability was noted in people suffering from lower back pain for flexion and lateral flexion. A significant heterogeneity was found between the studies which lacked some details and standardization of the criteria which were used for defining patients with lower back pain or without them (control group). Results show that spinal pain is the main reason behind the limitation of lumbar range of motion. It is clear from the data set of mean and standard deviation, and this is clear to establish the relationship between the causes of pelvic and spinal pain. In flexion-based ROM, the mean difference was found to be -9.77 (95% CI: -21.86, 2.32). Similarly, for lateral flexion, the mean difference was found to be -5.58 (with 95% CI: -10.38, -0.79). It can be concluded that spinal disease is too influential for people; thereby, it affects day-to-day life activities by creating painful and restricted movements. It is concluded that people suffering from lower back pain have reduced proprioception and range of movement in the lumbar region when compared to control groups with no lower back pain, which mainly focus on flexion and lateral flexion.


In vitro phagocytosis of liquid-stored red blood cells requires serum and can be inhibited with fucoidan and dextran sulphate.
Red-blood-cells (RBCs) undergo structural and metabolic changes with prolonged storage, which ultimately may decrease their survival after transfusion. Although the storage-induced damage to RBCs has been rather well described biochemically, little is known about the mechanisms underlying the recognition and rapid clearance of the damaged cells by macrophages. We, here, used a murine model for cold (+4°C) RBC storage and transfusion. Phagocytosis of human or murine RBCs, liquid stored for 6-8 weeks or 10-14 days, respectively, was investigated in murine peritoneal macrophages. The effects of storage on murine RBCs resembled that described for stored human RBCs with regard to decreased adenosine triphosphate (ATP) levels, accumulation of microparticles (MPs) during storage, and RBC recovery kinetics after transfusion. Under serum-free conditions, phagocytosis of stored human or murine RBCs in vitro was reduced by 70-75%, as compared with that in the presence of heat-inactivated fetal calf serum (FCS). Human serum promoted phagocytosis of stored human RBCs similar to that seen with FCS. By adding fucoidan or dextran sulphate (blockers of scavenger receptors class A (SR-A)), phagocytosis of human or murine RBCs was reduced by more than 90%. Phagocytosis of stored human RBCs was also sensitive to inhibition by the phosphatidylinositol 3 kinase-inhibitor LY294002, the ERK1/2-inhibitor PD98059, or the p38 MAPK-inhibitor SB203580. RBCs damaged during liquid storage may be recognized by macrophage SR-A and serum-dependent mechanisms. This species-independent recognition mechanism may help to further understand the rapid clearance of stored RBCs shortly after transfusion.


Amphetamines in child medicine: a review of ClinicalTrials.gov.
Background: Globally, the use of amphetamines as therapeutic agents in pediatric medicine is a crucial area of concern, especially given the population's vulnerability. Methods: On 6 August 2023, a search was conducted on ClinicalTrials.gov using "amphetamine" as the keyword. Two independent examiners screened trials against set criteria, including a focus on amphetamine, completion status, an interventional approach, and included children. Ongoing or observational studies were excluded. Data extracted from the qualified trials encompassed primary objectives, participant counts, study duration, and outcomes, with the aim of analyzing children disorders treated by amphetamine. Results: On 6 August 2023, a search of the ClinicalTrials.gov database with the term "amphetamines" identified 179 clinical trials. After extensive exclusion criteria, 19 trials were ultimately selected for analysis. The predominant condition under investigation was attention deficit hyperactivity disorder (ADHD), present in 84.2% of studies. Key study characteristics included: phase 4 trials (36.8%), randomized allocation (63.2%), and the parallel intervention model (42.1%). Masking techniques varied, with no masking in 42.1% of studies, and double and quadruple masking both accounting for 21.1%. Geographically, 78.9% of the studies' participants were from the United States. Conclusion: This study highlights the notable therapeutic potential of amphetamines in pediatric ADHD populations and emphasizes the importance of recognizing potential side effects and addiction risks. As pharmacogenomics offers the prospect of personalized treatments, there is potential to increase therapeutic efficacy and decrease adverse reactions. It is vital to balance these benefits against the inherent risks, understanding the need for continued research to optimize the use of amphetamines in medicine.


Dbp5p, a cytosolic RNA helicase, is required for poly(A)+ RNA export.
The DBP5 gene encodes a putative RNA helicase of unknown function in the yeast Saccharomyces cerevisiae. It is shown here that Dbp5p is an ATP-dependent RNA helicase required for polyadenylated [poly(A)+] RNA export. Surprisingly, Dbp5p is present predominantly, if not exclusively, in the cytoplasm, and is highly enriched around the nuclear envelope. This observation raises the possibility that Dbp5p may play a role in unloading or remodeling messenger RNA particles (mRNPs) upon arrival in the cytoplasm and in coupling mRNP export and translation. The functions of Dbp5p are likely to be conserved, since its potential homologues can be found in a variety of eukaryotic cells.


Comparison of Intrauterine Antibiotics versus Ozone Medical Use in Sheep with Retained Placenta and Following Obstetric Assistance.
This study outlines a new approach to reproductive tract treatment using ozone foam spray for certain ovine obstetrical problems, such as retained foetal membranes and possible uterine infections following obstetric assistance (OA), in comparison with classical antibiotics treatments. The study was conducted on 256 ewes from 11 sheep farms in north-western Croatia. A total of 139 ewes were diagnosed with dystocia (DT) and 49 with retention of placenta (RP). Ewes with RP were treated either with ozone foam spray (Riger spray G; Novagen(®) ) applied into the body of the uterus for 2-3 s (first or RPO group; n = 24) or with two foaming, intrauterine tablets of oxytetracycline hydrochloride (Geomycin(®) F) (second or RPA group; n = 25). The third and fourth groups consisted of ewes that received OA for dystocia (including ringwomb, foetal oversize and assistance of abnormal position and posture). The third group (DTO; n = 70) was treated with ozone foam spray, while ewes in fourth group (DTA; n = 69) were treated with antibiotics. The ewes in the control group (CTL) with physiological puerperium were randomly selected (n = 70) from all herds. Transrectal ultrasonography (transversal diameter of uterine horns) was used for the control of uterus regression on days 2 and 25 after parturition. There was a difference in transversal uterine horn diameter in the RP groups, that is RPO and RPA (5.40 ± 0.53 cm vs. 5.43 ± 0.40 cm), ewes with dystocia, that is DTO and DTA (5.37 ± 0.49 cm vs. 5.54 ± 0.60 cm) and ewes from the CTL group (4.98 ± 0.35 cm) one day after parturition. Average transversal uterine diameter of all groups at day 25 post-partum was 1.80 ± 0.15 cm. The intrauterine ozone treatment in ewes with RP and after manual obstetrics attained similar results to spontaneously delivered ewes (CTL group), showed as the physiological regression of the uterus with a similar transversal diameter without the presence of lochia in the uterine lumen, indicating that this could be a novel potential alternative therapy.


Look beyond the red eyes!
This is a case of a 63-year-old gentleman who presented with persistent red eyes to the eye clinic for several months. He had been seen in the eye department on several visits when he was noted to have red ears too. This led to further review in the rheumatology and ear, nose and throat clinic to confirm the diagnosis of relapsing polychondritis. He was treated successfully with systemic steroids.


[Specific regulation of gene expression in brain by antisense oligodeoxynucleotides].
The synthetic oligodeoxynucleotide (ODN) complementary to the normal (sense) mRNA, so-called antisense ODN, has been used to regulate the gene expression in the brain. It has been reported to interfere with transcription, pre-mRNA splicing and translation through at least two mechanisms; i.e., its competition with transcription and protein synthesis machinery or induction of mRNA cleavage. The unmodified antisense ODN was shown to be the RNase activator when it hybridizes with at least four contiguous bases of mRNA. In contrast, the phosphorothioate ODN (S-ODN) is reported to be a less effective activator of RNas II and more resistant to the nuclease attack than unmodified ODN. Because of these properties, S-ODNs are preferentially employed in antisense ODN experiments. When the DNA sequence of the target gene is determined, we can design an antisense ODN that selectively hybridizes with the bases of a nucleic acid (DNA or RNA) related to the target gene. The initial sites of specific binding of most drugs are known to be proteins such as receptors and enzymes. Therefore, the specific modulation of target protein synthesis by the antisense ODN method is quite interesting to the pharmacologist. We have studied the change in the morphine-induced behaviors after the microinjection of antisense S-ODN directed against the m-opioid receptor (MOR) into the periaqueductal gray (PAG) or lateral ventricle of rat brain. We could detect the decrease of the MOR mRNA level in PAG by the RT-PCR method and that in whole brain by the Northern blot technique. Although the antisense ODN method seems to be quite useful for the modulation of a given gene expression, many problems still remain to be elucidated. These include the mechanism of the regulation of a target gene, pharmacokinetics of antisense ODN and toxicity of antisense ODN.


Local hypertrichosis: A rare complication of a temporary henna tattoo.
Temporary henna tattoos have become increasingly widespread among children and young people, especially in holiday spots in recent years. Although reactions to henna tattoo are becoming progressively more common, only few cases of a henna pseudo-tattoo resulting in temporary hypertrichosis have been reported so far. Here, we have reported a 5-year-old girl who developed allergic contact dermatitis and localized hypertrichosis on her right arm after application of temporary henna tattoo during summer holiday.


Malnutrition and associated clinical outcomes in hospitalized patients aged 60 and older: an observational study in rural Wales.
This is a prospective observational study of malnutrition and six-week clinical outcomes on a previously unstudied population of older hospital inpatients in rural Wales. One hundred and twenty-six of 152 patients older than 60 years identified on the wards surveyed were included. Patients unable to give informed consent and those too ill to participate were excluded. The main findings were that 55 (44%) were malnourished at the first assessment, that nutrition risk predicted mortality (P = 0.019), length of hospital stay (P = 0.026), and discharge destination (P = 0.005), that only 17 patients had received nutritional support, and that many of those who received support nevertheless had lost weight at the 6-week follow-up. This confirms previous research which suggests that, while malnutrition is associated with poorer clinical outcomes, nutrition support for older patients in hospital nevertheless is often insufficient.


Characteristics of phi T, the temperate bacteriophage carried by Bacillus megaterium 899a.
Phage T was the only phage observed in lysates of Bacillus megaterium 899a induced with mitomycin C, 0.35 mug/ml. The phage adsorbed slowly to its host in nutrient agar, giving rise to plaques of varying sizes and turbidity. Only clear plaques were observed when the phage and host cells were preincubated in an adsorption buffer and plated under optimum conditions. Plaque turbidity was caused by either the addition of 0.5 x 10(-2) to 1.0 x 10(-2) M CaCl(2) to the phage assay medium, or by raising the incubation temperature to 34 C. Phage T purified on a CsCl gradient had a density of 1.48 g/ml in CsCl and the extracted phage DNA had a buoyant density in CsCl of 1.6975 g/ml, equivalent to 38.2% guanine plus cytosine. The phage was rapidly inactivated at 75 C and was unstable in the presence of chloroform at 4 C, but it was stable in buffer stored in ice. When stage I sporulating cells were induced with mitomycin C, phage were carried into spores which when germinated lyse with the release of phi T. The burst size on induction of early-log vegetative cells was 52, whereas the burst size of induced T(0) sporulating cells, diluted in fresh medium, was 47 for a sporulating strain and 140 for an asporogenous mutant. A typical phage T had a long, noncontracting tail 240 nm long, 9 to 11 nm wide, with a repeating disk unit along the tail, 4 nm in size center to center. The tail ended in a small disk (15 nm wide) which is presumably for attachment to the host. The hexagonal head measures 68 by 57 nm and is composed of donut-shaped units 9 nm in diameter.


High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells.
Scatchard analysis of binding of 125I-basic fibroblast growth factor (FGF) to baby hamster kidney (BHK) cells revealed the presence of two binding sites: a high affinity site with KD of 20 pM and 80,000 sites per cell and a low affinity site with KD of about 2 nM and 600,000 sites per cell. The binding to the two sites could be separated by first washing the cells with 2 M NaCl at pH 7.5 which released the low affinity binding and then extracting the cells with 0.5% Triton X-100 to recover the 125I-basic FGF bound to high affinity sites. The binding to the high affinity site was acid sensitive, suggesting that it represented binding to the receptor. Binding to the low affinity site could be competed strongly by heparin and less strongly by heparan sulfate but not by chondroitin sulfate, dermatan sulfate, or keratan sulfate. Treatment of BHK cells with heparinase abolished 62% of the low affinity binding, suggesting that the low affinity binding represented binding to cell-associated, heparin-like molecules. A variety of other cell types, including bovine capillary endothelial (BCE) cells, also demonstrated both low and high affinity binding sites. To test whether the low affinity binding might play a role in the basic FGF stimulation of plasminogen activator (PA) production by BCE cells, heparin was added to BCE cultures at concentrations which totally blocked binding of 125I-basic FGF to the low affinity sites. Addition of the heparin did not diminish the increased PA production induced by basic FGF. This suggests that the low affinity binding has no direct role in the stimulation of PA production in BCE cells.


In vitro synergy of the combination of sulbactam-durlobactam and cefepime at clinically relevant concentrations against A. baumannii, P. aeruginosa and Enterobacterales.
Sulbactam-durlobactam is a potent combination active against Acinetobacter baumannii; however, it lacks activity against other nosocomial pathogens. Cefepime is a common first-line therapy for hospital/ventilator-associated pneumonia caused by Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacterales. With increasing resistance to cefepime, and the significant proportion of polymicrobial nosocomial infections, effective therapy for infections caused by Acinetobacter baumannii, P. aeruginosa and Enterobacterales is needed. This study investigated the in vitro synergy of sulbactam-durlobactam plus cefepime against relevant pathogens. Static time-kills assays were performed in duplicate against 14 cefepime-resistant isolates (A. baumannii, n = 4; P. aeruginosa, n = 4; Escherichia coli, n = 3; Klebsiella pneumoniae, n = 3). One WT K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients. Sulbactam-durlobactam alone showed significant activity against A. baumannii consistent with the MIC values. Sulbactam-durlobactam plus cefepime showed synergy against one A. baumannii isolate with an elevated MIC to sulbactam-durlobactam (32 mg/L). Against all P. aeruginosa isolates, synergy was observed with sulbactam-durlobactam plus cefepime. For the Enterobacterales, one E. coli isolate demonstrated synergy while the others were indifferent due to significant kill from sulbactam-durlobactam alone. The combination of sulbactam-durlobactam plus cefepime showed synergy against one of the K. pneumoniae and additive effects against the other two K. pneumoniae tested. No antagonism was observed in any isolates including the WT strain. Synergy and no antagonism was observed with a combination of sulbactam-durlobactam and cefepime; further in vivo pharmacokinetic/pharmacodynamics data and clinical correlation are necessary to support our findings.


Effect of Temperature and Host Life Stage on Efficacy of Soil Entomopathogens Against the Swede Midge (Diptera: Cecidomyiidae).
The Swede midge, Contarinia nasturtii Kieffer, is an economically significant pest of cruciferous crops in Canada and the northeastern United States. The effect of temperature on the virulence of three entomopathogenic nematode species, Heterorhabditis bacteriophora, Steinernema carpocapsae, and Steinernema feltiae, the entomopathogenic fungus Metarhizium brunneum, and a H. bacteriophora+M. brunneum combination treatment to C. nasturtii larvae, pupae, and cocoons was investigated. In the laboratory, all three nematode species successfully reproduced inside C. nasturtii larvae: H. bacteriophora produced the highest number of infective juveniles per larva, followed by S. carpocapsae and S. feltiae. H. bacteriophora and the H. bacteriophora+M. brunneum combination treatment generally caused the highest mortality levels to all C. nasturtii life stages at 20°C and 25°C, whereas S. feltiae caused the highest mortality to larvae and pupae at 16°C. No nematode species caused significant mortality when applied in foliar treatments to the infested host plant meristem and, in spite of high mortality, an antagonistic interaction was observed in the H. bacteriophora+M. brunneum combination treatment when compared with expected mortality. In trials conducted in broccoli fields in Elora, Ontario, M. brunneum suppressed adult emergence of C. nasturtii from infested soil in 2012 and all nematode treatments successfully suppressed adult emergence in 2013; however, no significant effects were observed in field trials conducted in Baden, Ontario.


Shift work at a modern offshore drilling rig.
The oil and gas exploration and production offshore units are classified as hazardous installations. Work in these facilities is complex, confined and associated with a wide range of risks. The continuous operation is secured by various shift work patterns. The objective of this study was to evaluate how offshore drilling workers perceived shift work at high seas and its impacts on their life and working conditions. The main features of the studied offshore shift work schedules are: long time on board (14 to 28 days), extended shifts (12 hours or more per day), slow rotation (7 to 14 days in the same shift), long sequence of days on the night shift (7 to 14 days in a row) and the extra-long extended journey (18 hours) on shift change and landing days. Interviews revealed a wide range of stressors caused by the offshore shift work, as well as difficulties to conciliate work with family life. It was observed that changes of the family model, leading to role conflicts and social isolation, work in a hazardous environment, perceiving poor sleep when working at night shifts and the imbalance between the expected and actual rewards are the major stressors for the offshore drilling workers.


[Desipramine-induced down regulation of beta-adrenergic receptors: effects of noradrenergic and serotonergic neuronal activities and of alpha 2-adrenergic receptor mediated mechanisms].
The mechanisms of antidepressant (desipramine)-induced down regulation of beta-adrenergic receptors were investigated. The number of beta-adrenergic receptors in rat cerebral cortex was increased by the destruction of norepinephrine (NE) neurons with 6-hydroxydopamine or DSP-4 pretreatments. Desipramine (DMI)-induced down regulation of beta-receptors was completely prevented by these procedures, whereas the destruction of serotonin (5-HT) neurons neither changed the receptor number nor prevented the DMI-induced down regulation. The number of beta-adrenergic receptors showed a decrease within 3 days by treatment of DMI plus (+) mianserin or yohimbine which promotes NE and 5-HT release from nerve endings through presynaptic alpha 2-adrenergic antagonism. Another alpha 2-adrenergic antagonist (-)mianserin, which promotes only 5-HT release, also accelerated the down regulation induced by DMI, but this acceleration was not prevented by the destruction of 5-HT neurons. Combination of DMI with 5-HT releasing agent methiothepin (5-HT autoreceptor antagonist) did not accelerate beta-receptor down regulation. These results suggest that 1) NE availability in the synaptic cleft plays a significant role in the regulation of beta-receptor number, but 2) postsynaptic alpha 2-adrenergic mechanisms also seem to contribute to the regulation, whereas 3) 5-HT neurons have no significant effect on the process.


A robust preference for cheap-and-easy strategies over reliable strategies when verifying personal memories.
People depend on various sources of information when trying to verify their autobiographical memories. Yet recent research shows that people prefer to use cheap-and-easy verification strategies, even when these strategies are not reliable. We examined the robustness of this cheap strategy bias, with scenarios designed to encourage greater emphasis on source reliability. In three experiments, subjects described real (Experiments 1 and 2) or hypothetical (Experiment 3) autobiographical events, and proposed strategies they might use to verify their memories of those events. Subjects also rated the reliability, cost, and the likelihood that they would use each strategy. In line with previous work, we found that the preference for cheap information held when people described how they would verify childhood or recent memories (Experiment 1), personally important or trivial memories (Experiment 2), and even when the consequences of relying on incorrect information could be significant (Experiment 3). Taken together, our findings fit with an account of source monitoring in which the tendency to trust one's own autobiographical memories can discourage people from systematically testing or accepting strong disconfirmatory evidence.


Monocytes Differentiate to Immune Suppressive Precursors of Metastasis-Associated Macrophages in Mouse Models of Metastatic Breast Cancer.
Metastasis-associated macrophages (MAMs) play pivotal roles in breast cancer metastasis by promoting extravasation and survival of metastasizing cancer cells. In a metastatic breast cancer mouse model, we previously reported that circulating classical monocytes (C-MOs) preferentially migrated into the tumor-challenged lung where they differentiated into MAMs. However, the fate and characteristics of C-MOs in the metastatic site has not been defined. In this study, we identified that adoptively transferred C-MOs (F4/80lowCD11b+Ly6C+) differentiated into a distinct myeloid cell population that is characterized as F4/80highCD11bhighLy6Chigh and gives rise to MAMs (F4/80lowCD11bhighLy6Clow) within 18 h after migration into the metastatic lung. In mouse models of breast cancer, the CD11bhighLy6Chigh MAM precursor cells (MAMPCs) were commonly found in the metastatic lung, and their accumulation was increased during metastatic tumor growth. The morphology and gene expression profile of MAMPCs were distinct from C-MOs and had greater similarity to MAMs. For example MAMPCs expressed mature macrophage markers such as CD14, CD36, CD64, and CD206 at comparable levels with MAMs, suggesting that MAMPCs have committed to a macrophage lineage in the tumor microenvironment. MAMPCs also expressed higher levels of Arg1, Hmox1, and Stab1 than C-MOs to a comparable level to MAMs. Expression of these MAM-associated genes in MAMPCs was reduced by genetic deletion of colony-stimulating factor 1 receptor (CSF1R). On the other hand, transient CSF1R blockade did not reduce the number of MAMPCs in the metastatic site, suggesting that CSF1 signaling is active in MAMPCs but is not required for their accumulation. Functionally MAMPCs suppressed the cytotoxicity of activated CD8+ T cells in vitro in part through superoxide production. Overall, our results indicate that immediately following migration into the metastatic tumors C-MOs differentiate into immunosuppressive cells that have characteristics of monocytic myeloid-derived suppressor cell phenotype and might be targeted to enhance efficacy of immunotherapy for metastatic breast cancer.


Bilateral sudden sensorineural hearing loss caused by leptomeningeal carcinomatosis: case report and review.
Leptomeningeal carcinomatosis is a rare condition characterized by diffuse infiltration of the meninges after the metastasis of the solid tumors. Bilateral sudden hearing loss is a rare initial symptom. In this article, we report a 44-year-old male patient with bilateral sudden hearing loss and dizziness. Magnetic resonance imaging showed involvement of the bilateral vestibulocochlear nerves. Malignant cells were detected in cerebrospinal fluid cytology. To the best of our knowledge, leptomeningeal carcinomatosis due to duodenum adenocarcinoma has not been reported before in the English literature. Leptomeningeal carcinomatosis should be kept in mind in patients who have bilateral sudden sensorineural hearing loss.


Productivity Benefits of Medical Care: Evidence from US-Based Randomized Clinical Trials.
One of the key recommendations of the Second Panel on Cost-Effectiveness in Health and Medicine is to take a societal perspective when evaluating new technologies-including measuring the productivity benefits of new treatments. Yet relatively little is known about the impact that new treatments have on labor productivity. To examine the relationship between new drug treatments and gains in labor productivity across conditions in the United States and to evaluate which randomized clinical trials (RCTs) collected labor productivity data. We collected data on US-based RCTs with work-ability surveys from searches of Google Scholar, PubMed, Scopus, the Cochrane Central Registry of Clinical Trials, and ClinicalTrails.gov. Combining RCT data with survey data from the Medical Expenditure Panel Survey, we assessed productivity changes from new drug treatments. During the last decade, some disease conditions have seen treatments that improve ability to work by as much as 60%. The annual increase in productivity gains attributable to new drug treatments was modest 1.1% (P = 0.53). Of the 5092 RCTs reviewed, ability-to-work measures were collected in 2% of trials. Work productivity surveys were more likely among prevalent medical conditions that affected individuals who worked, earned higher wages, and experienced larger reductions in hours worked as a consequence of disease diagnosis. From our data, we estimated that drug innovation increased productivity by 4.8 million work days per year and $221 billion in wages per year. These labor-sector benefits should be taken into account when assessing the socially optimal cost for new drug innovation.


Time-resolved ion flux measurements in pulsed, electron-beam-generated plasmas.
Time-resolved ion flux and energy distributions were measured at an electrode located adjacent to pulsed, electron-beam-generated plasmas in argon and oxygen. Temporal variations in the incident Ar+, O+, and O(2)+ energy and flux were correlated to changes in the electron temperature and plasma density. The decay time of the oxygen plasma is found to be shorter than that of the argon plasma, which is understood by considering the different loss mechanisms of each ion species.


Mass spectrometric characterization of 3'-imino[60]fulleryl-3'-deoxythymidine by collision-induced dissociation.
The primary structure of 3'-imino[60]fulleryl-3'-deoxythymidine ions is studied using mass spectrometry both in the positive and negative modes. Interaction between the subunits is discussed using collision-induced dissociation (CID) spectra. Collisional activation with argon of the sodiated cations leads to the cleavage of the glycosidic bond and the transfer of a radical hydrogen from the deoxyribose to the thymine. The sodiated thymine is the only fragment observed for low collision energies in the positive mode. In the negative mode, two different ionization mechanisms take place, reduction and deprotonation in the presence of triethylamine. The 2.7 eV electron affinity of C60 and its huge cross section compared to the small cross section and predicted 0.44 eV electron affinity of the thymidine subunit most likely localize the radical electron on the fullerene. On the other hand, deprotonation of the 3'-azido-3'-deoxythymidine (AZT) is known to occur in N-3, the most acidic site of the nucleobase. Consequently, deprotonation causes the negative charge to be initially localized on the thymine. Both types of parent anions give the radical anion C60*- as fragment. The other fragments detected are the dehydrogenated 3'-imino[60]fulleryl-3'-deoxyribose anion, C60NH2-, C60N- and C60H-. Since in negative ion mass spectrometry all fragments include the [60]fullerene unit, this suggests that the fragmentation is driven by the electron affinity of the [60]fullerene, likely responsible for a charge transfer between the deprotonated thymine and the C60.


Predicting Prolonged Stay in the ICU Attributable to Bleeding in Patients Offered Plasma Transfusion.
In blood transfusion studies, plasma transfusion (PPT) and bleeding are known to be associated with risk of prolonged ICU length of stay (ICU-LOS). However, as patients can show significant heterogeneity in response to a treatment, there might exists subgroups with differential effects. The existence and characteristics of these subpopulations in blood transfusion has not been well-studied. Further, the impact of bleeding in patients offered PPT on prolonged ICU-LOS is not known. This study presents a causal and predictive framework to examine these problems. The two-step approach first estimates the effect of bleeding in PPT patients on prolonged ICU-LOS and then estimates risks of bleeding and prolonged ICU-LOS. The framework integrates a classification model for risks prediction and a regression model to predict actual LOS. Results showed that the effect of bleeding in PPT patients significantly increases risk of prolonged ICU-LOS (55%, p=0.00) while no bleeding significantly reduces ICU-LOS (4%, p=0.046).


Decisions to Attend and Drink at Party Events: The Effects of Incentives and Disincentives and Lifetime Alcohol and Antisocial Problems.
Alcohol use disorders are associated with patterns of impulsive/risky decision making on behavioral economic decision tasks, but little is known about the factors affecting drinking-related decisions. The effects of incentives and disincentives to attend and drink at hypothetical alcohol-related party events as a function of lifetime (LT) alcohol and antisocial problems were examined in a sample of 434 young adults who varied widely in LT alcohol and antisocial problems. Moderate and high disincentives substantially discouraged decisions to attend the party events and were associated with decisions to drink less at the party events. High versus low party incentives were associated with more attendance decisions. LT antisocial problems were associated with being less deterred from attending by moderate and high disincentives. LT alcohol problems were associated with greater attendance at high party incentive contexts. LT alcohol problems were associated with drinking more at the majority of events; however, the results indicate that young adults with high levels of alcohol problems moderate their drinking in response to moderate and high disincentives. Finally, attendance and drinking decisions on this hypothetical task were significantly related to actual drinking practices. The results suggest that antisocial symptoms are associated with a reduced sensitivity to the potential negative consequences of drinking, while alcohol problems are associated with a greater sensitivity to the rewarding aspects of partying. The results also underline the value of directly assessing drinking-related decisions in different hypothetical contexts as well as assessing decisions about attendance at risky drinking events in addition to drinking amount decisions.


Prevalence and trends of metabolic syndrome in Korea: Korean National Health and Nutrition Survey 1998-2001.
Metabolic syndrome (MetS) is a major international health problem. Limited information is available about the prevalence of MetS in Asia, especially in Korea. To examine the prevalence and trends of MetS in a Korean population. In addition, we investigated the risk factors associated with MetS. A total of 7445 participants aged >/=20 years from the Korean National Health and Nutrition Survey (KNHNS) 1998 and 5964 participants from the KNHNS 2001 were included in this analysis. The KNHNS is a cross-sectional health survey of a nationally representative sample of the Korean population. The prevalence of MetS was determined using the National Cholesterol Education Program Adult Treatment Panel III criteria and the Asia-Pacific criteria for obesity based on waist circumference (APC-WC). Using the ATP III criteria, the age-adjusted prevalence of MetS among Korean adults was 15.7% (13.7% male, 17.8% female) in 1998 and 14.4% (13.0% male, 16.2% female) in 2001. Using the APC-WC criteria, the prevalence was 21.6% (19.4% male, 23.9% female) in 1998 and 21.4% (20.1% male, 23.4% female) in 2001. Of the five MetS components, increasing trends were found between 1998 and 2001 in the prevalence of hypertriglyceridaemia, low high-density lipoprotein cholesterol and central obesity for both men and women. Age, sex, body mass index and a family history of diabetes were associated with MetS. These results from a representative sample show that MetS is common in Korean adults. A systemic public health programme is required to prevent future increases in diabetes and cardiovascular complications.


Clinical outcomes of generic versus brand-name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study.
Skepticism exists among healthcare workers and patients regarding the efficacy and safety of generic medication, despite its potential to lower healthcare costs. This study aimed to compare the outcomes of a generic clopidogrel and its brand-name counterpart for secondary prevention in patients with acute myocardial infarction (AMI). Using the Taiwan National Health Insurance Research Database, we identified 49,325 patients who were hospitalized for AMI between January 1, 2008 and December 31, 2013 and prescribed either generic or brand-name clopidogrel. Among them, 2419 (4.9%) were prescribed the generic clopidogrel. After propensity score matching, both the generic and brand-name groups consisted of 2382 patients. The primary efficacy outcome was a composite of myocardial infarction, coronary revascularization, ischemic stroke, and all-cause death. The primary safety outcome was major bleeding requiring hospitalization. At a mean follow-up of 2.5 years, the generic and brand-name clopidogrel groups had comparable risks of primary efficacy outcome (41.9% vs. 42%; hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.88-1.04), and the risks of the individual components were also similar. There were no significant differences between the two groups in major bleeding (7.9% vs. 7.9%; HR 0.99; 95% CI 0.81-1.21). Subgroup analyses also revealed no statistically significant interactions between the treatment effect and various subgroups. In this retrospective database analysis, the generic clopidogrel was comparable to its brand-name counterpart regarding cardiovascular and bleeding outcomes for the treatment of patients with AMI.


Case Report: A recurrent case of ALK-ALCL after autologous transplantation was successfully treated with BV + a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome with the addition of chidamide maintenance therapy.
ALK-negative anaplastic large cell lymphoma (ALK-ALCL) is a rare heterogeneous malignancy of T-cell origin.ALK- ALCL has a poor prognosis, with more patients experiencing relapses and refractory to treatment, and its treatment remains challenging. We report a case with bone involvement as the main clinical manifestation of recurrent, and the patient achieved significant partial remission after brentuximab vedotin(BV) combined with a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome (PLM60) with the addition of chidamide maintenance therapy and received regular follow-up, with a disease-free survival of 16 months to date. A literature review of the clinical presentation and treatment of ALCL was also conducted to identify strategies for its diagnosis and management. ALK-ALCL with bone involvement as the main manifestation of recurrent is relatively rare. Here, BV combined a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome was applied for the first time in a patient with relapsed ALK-ALCL, inducing remission and extending survival. However, further prospective studies with many patients are needed to determine the biological characteristics of this rare type of ALK-ALCL and relevant treatment strategies.


Synthesis of [N-methyl-3H]-7-chloro-1,3-dihydro-5-(2-fluorophenyl)-1-methyl-2 H-1,4-benzodiazepin-2- one (3H-fludiazepam) by phase transfer catalysis.
[N-methyl-3H]-7-Chloro-1,3-dihydro-5-(2-fluorophenyl)-1-methyl-2H-1,4- benzodiazepin-2- one ( [3H]fludiazepam) was prepared by phase transfer catalytic N-methylation of the corresponding nor-derivative with [3H]methyl iodide [407 GBq/mmol (11 Ci/mmol)] in a radiochemical yield of 34%. The specific activity was 271.6 GBq/mmol (7.34 Ci/mmol).


Prolyl hydroxylase activity as an index of liver damage induced by ethanol.
It was found that chronic intoxication of rats with ethanol results in an increase of prolyl hydroxylase activity in liver and serum of the experimental animals. The increase of enzyme activity precedes the morphological symptoms of liver damage. The possibility arises that the assay of prolyl hydroxylase in serum or in liver biopsy samples could be useful for the diagnosis of the tendency of some individuals to develop liver cirrhosis induced by ethanol.


Assessment of occupational doses from internal contamination with 241Am.
A group of workers with occupational intakes of 241Am, which occurred a long time ago, has been followed for some time. Results of in vivo measurement and bioassay of excreta are compared with the values predicted by the ICRP Publication 78 model. The observed skeletal content is, as a rule, higher than the predicted one. The ratio of excreted activity in urine to that in faeces is in very good agreement with the model prediction. Another group of workers from a waste management department, who were internally contaminated in July 2001, has also been followed. In some cases, there is quite a large difference in calculated intake between excretion by urine and that by faeces. The contaminant was presumably the same as that in the group of workers with old intakes, but its physical and chemical form could be influenced by a fixating lacquer used to prevent the spread of contamination.


Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis.
Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China's experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.


Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain.
mRNA of cytochrome P450 21-hydroxylase (P450c21) is expressed in the brain, but little is known about the enzymatic properties of P450c21 in the brain. In the present study, we showed, by using various recombinant cytochrome P450 (CYP)2D enzymes and anti-CYP2D4- or P450c21-specific antibodies, that rat brain microsomal steroid 21-hydroxylation is catalyzed not by P450c21, but by CYP2D isoforms. Rat CYP2D4 and human CYP2D6, which are the predominant CYP2D isoforms in the brain, possess 21-hydroxylation activity for both progesterone and 17alpha-hydroxyprogesterone. In rat brain microsomes, these activities were not inhibited by anti-P450c21 antibodies, but they were effectively inhibited by the CYP2D-specific chemical inhibitor quinidine and by anti-CYP2D4 antibodies. mRNA and protein of CYP2D4 were expressed throughout the brain, especially in cerebellum, striatum, pons, and medulla oblongata, whereas the mRNA and protein levels of P450c21 were extremely low or undetectable. These results support the idea that CYP2D4, not P450c21, works as steroid 21-hydroxylase in the brain. Allopregnanolone, a representative gamma-aminobutyric acid receptor modulator, was also hydroxylated at the C-21 position by recombinant CYP2D4 and CYP2D6. Rat brain microsomal allopregnanolone 21-hydroxylation was inhibited by fluoxetine with an IC(50) value of 2 microm, suggesting the possibility that the brain CYP2D isoforms regulate levels of neurosteroids such as allopregnanolone, and that this regulation is modified by central nervous system-active drugs such as fluoxetine.


Developing Your Evaluation Plans: A Critical Component of Public Health Program Infrastructure.
A program's infrastructure is often cited as critical to public health success. The Component Model of Infrastructure (CMI) identifies evaluation as essential under the core component of engaged data. An evaluation plan is a written document that describes how to monitor and evaluate a program, as well as how to use evaluation results for program improvement and decision making. The evaluation plan clarifies how to describe what the program did, how it worked, and why outcomes matter. We use the Centers for Disease Control and Prevention's (CDC) "Framework for Program Evaluation in Public Health" as a guide for developing an evaluation plan. Just as using a roadmap facilitates progress on a long journey, a well-written evaluation plan can clarify the direction your evaluation takes and facilitate achievement of the evaluation's objectives.


Probabilistic growth of large entangled states with low error accumulation.
The creation of complex entangled states, resources that enable quantum computation, can be achieved via simple "probabilistic" operations which are individually likely to fail. However, typical proposals exploiting this idea carry a severe overhead in terms of the accumulation of errors. Here, we describe a method that can rapidly generate large entangled states with an error accumulation that depends only logarithmically on the failure probability. We find that the approach may be practical for success rates in the sub-10% range. The assumptions that we make, including parallelism and high connectivity, are appropriate for real systems including those based on measurement-induced entanglement. This result therefore indicates the feasibility of such devices.


Deoxycytidine kinase and deoxycytidine deaminase values correspond closely to clinical response to cytosine arabinoside remission induction therapy in patients with acute myelogenous leukemia.
In this study, it has been shown that in 21 patients with AML the dCyd kinase and dCyd deaminase activities correspond closely to the clinical response to ara-C remission induction therapy. Patients with primary disease were treated with a conventional-dose ara-C regimen whereas nonresponders and relapsed patients followed an ID ara-C regimen (1 g/m2 X 12). Of these 21 patients (11 with primary disease and ten relapsed), seven had ara-C resistant disease (three primary and four relapsed patients). Five of the seven patients had a very low dCyd kinase and normal dCyd deaminase activity, whereas the other two had a normal dCyd kinase and an increased dCyd deaminase activity.


Transition from metal-DTH resistance to susceptibility is facilitated by NLRP3 inflammasome signaling induced Th17 reactivity: Implications for orthopedic implants.
Metal hypersensitivity has been recognized as an adverse biologic reaction that can compromise total joint arthroplasty (TJA) performance. However, the etiology of metal hypersensitivity responses in TJAs remains unclear. Metal implant debris is known to act as a danger signal that drives NLRP3 inflammasome activation. It remains unknown if implant debris induced inflammasome activation regulates T cell lineage in TJA metal hypersensitivity responses. In this study, we show both in vivo and in vitro that the pathogenesis of metal hypersensitivity responses to implant debris are largely dependent on activation of the inflammasome/caspase-1 pathway and subsequent production of IL-17A/F by CD4+ T cells. Inhibiting either the inflammasome pathway or IL-17A bioactivity in vivo and in vitro (in vivo using NLRP3 and Caspase-1 deficient mice or in vitro using blocking agents such as Capase-1 inhibitor, IL-1Ra and anti-IL-17A), significantly (p<0.05) mitigated metal-DTH paw inflammation as well as lymphocyte cytokine (IFN-γ and IL-17) and proliferation responses in metal-sensitized mice and primary human PBMCs. This study provides mechanistic insight into how in vivo exposure to orthopedic implant debris, and metals in general, elicits NLRP3 inflammasome activation that mediates the generation of IL-17A/F producing CD4+ T cells, leading to metal-delayed type hypersensitivity reactions.


Drugs in space: Pharmacokinetics and pharmacodynamics in astronauts.
Space agencies are working intensely to push the current boundaries of human spaceflight by sending astronauts deeper into space than ever before, including missions to Mars and asteroids. Spaceflight alters human physiology due to fluid shifts, muscle and bone loss, immune system dysregulation, and changes in the gastrointestinal tract and metabolic enzymes. These alterations may change the pharmacokinetics and/or pharmacodynamics of medications used by astronauts and subsequently might impact drug efficacy and safety. Most commonly, medications are administered during space missions to treat sleep disturbances, allergies, space motion sickness, pain, and sinus congestion. These medications are administered under the assumption that they act in a similar way as on Earth, an assumption that has not been investigated systematically yet. Few inflight pharmacokinetic data have been published, and pharmacodynamic and pharmacokinetic/pharmacodynamic studies during spaceflight are also lacking. Therefore, bed-rest models are often used to simulate physiological changes observed during microgravity. In addition to pharmacokinetic/pharmacodynamic changes, decreased drug and formulation stability in space could also influence efficacy and safety of medications. These alterations along with physiological changes and their resulting pharmacokinetic and pharmacodynamic effects must to be considered to determine their ultimate impact on medication efficacy and safety during spaceflight.