Webcast marketing platform optimization via 6G R&D and the impact on brand content creation.
This work aims to investigate the development and management of cosmetics webcast marketing platforms, offering novel approaches for building and sustaining commercial brands. Firstly, an analysis of the current utilization of cosmetics webcast marketing platforms is conducted, identifying operational challenges associated with these platforms. Secondly, optimization strategies are proposed to address the identified issues by leveraging advancements in 6th Generation (6G) communication technology. Subsequently, a conceptual framework is established, employing big data interaction to examine the influence of webcast marketing platform experiences on brand fit. Multiple hypotheses are formulated to explore the relationship between platform experiences and brand fit. Finally, empirical analysis is performed within the context of the 5th Generation (5G) Mobile Communication Technology and extended to incorporate the 6G Mobile Communication Technology landscape. The results of the validation indicate the following: (1) the content generated by the webcast marketing platform has a positive impact on brand fit (β = 0.46, p<0.01; β = 0.31, p<0.05); (2) in the 6G network environment, a webcast marketing platform with high traffic transmission rates may enhance brand fit (β = 0.51, p<0.001); (3) the content generated by the webcast marketing platform exhibits significant positive regulatory effects on information-based and co-generated content (β = 0.42, p<0.01; β = 0.02, p<0.001). The findings of this work offer valuable insights for other scholars and researchers seeking to optimize webcast marketing platforms.


Gene expression profile of THP-1 cells treated with heat-killed Candida albicans.
Mechanisms under immune response against Candida albicans (C. albicans) remain largely unknown. To better understand the mechanisms of innate immune response against C. albicans, we analyzed the gene expression profile of THP-1 cells stimulated with heat-killed C. albicans. THP-1 cells were stimulated with heat-killed C. albicans for 9 hours at a ratio of 1:1, and gene expression profile of the cells was analyzed using Whole Human Genome Oligo Microarray. Differentially expressed genes were defined as change folds more than 2 and with statistical significance. Gene ontology (GO) and pathway analysis were used to systematically identify biological connections of differentially expressed genes, as well as the pathways associated with the immune response against C. albicans. A total of 355 genes were up-regulated and 715 genes were down-regulated significantly. The up-regulated genes were particularly involved in biological process of RNA processing and pathway of the spliceosome. In case of down-regulated genes, the particularly involved immune-related pathways were G-protein coupled receptor signaling pathway, calcium signaling pathway, MAPK signaling pathway and Ras pathway. We depict the gene expression profile of heat-killed C. albicans stimulated THP-1 cells, and identify the major pathways involved in immune response against C. albicans. These pathways are potential candidate targets for developing anti-C. albicans agent.


An efficient preparation of mulberroside a from the branch bark of mulberry and its effect on the inhibition of tyrosinase activity.
A bioactive ingredient in an ethanol extract from the branch bark of cultivated mulberry Husang-32 (Morus multicaulis Perr.) was isolated using a macroporous resin column. The primary component, which was purified by semi-preparative high-performance liquid chromatography diode array detection (HPLC-DAD), was identified as mulberroside A (MA) by liquid chromatograph-mass spectrometer (LC-MS), 1H and 13C nuclear magnetic resonance (NMR) spectra. In total, 4.12 g MA was efficiently extracted from one kilogram of mulberry bark. The enzymatic analysis showed that MA inhibited the generation of dopachrome by affecting the activities of monophenolase and diphenolase of tyrosinase in vitro. This analysis indicated that MA and oxyresveratrol (OR), which is the the aglycone of mulberroside A, exhibited strong inhibition of the monophenolase activity with IC50 values of 1.29 µmol/L and 0.12 µmol/L, respectively. However, the former showed weaker inhibitory activity than the latter for diphenolase. For the monophenolase activity, the inhibitory activity of MA and OR was reversible and showed mixed type 1 inhibition. Additionally, the inhibition constant KI (the inhibition constant of the effectors on tyrosinase) values were 0.385 µmol/L and 0.926 µmol/L, respectively, and the KIS (the inhibition constants of the enzyme-substrate complex) values were 0.177 µmol/L and 0.662 µmol/L, respectively. However, MA showed competitive inhibition of diphenolase activity, and KI was 4.36 µmol/L. In contrast, OR showed noncompetitive inhibition and KI = KIS = 2.95 µmol/L. Taken together, these results provide important information concerning the inhibitory mechanism of MA on melanin synthesis, which is widely used in whitening cosmetics.


Results of arthroscopic fixation of Mason type II radial head fractures using Kirschner wires.
The goals of this study are to report an arthroscopic technique for the treatment of Mason type II radial head fractures using Kirschner wires (K-wires), and investigate the feasibility and evaluate the results.We retrospectively review 18 cases of closed Mason type II radial head fractures treated in our institution from August 2010 to May 2015. There were 13 males and 5 females with an average age of 30.6 (17-45 years) years. Injuries were caused by falling in 8 cases, by traffic accidents in 5 cases, and by sports in 5 cases. The average time from injury to admission was 3.9 days (1-11 days). All radial head fractures were confirmed on x-ray and computed tomography. The fracture fragments were fixed with percutaneous K-wires under arthroscopy.All surgical wounds healed with primary closure, and no complication occurred, such as neurovascular injury, infection, or hardware failure. All patients were followed up for a mean period of 19 months (range: 14-29 months). Bone union was achieved for all patients with a mean time of 11 weeks. At final follow-up, range of motion of the elbow has no significant difference in comparison to the uninjured side. The mean Visual Analog Scale for these patients was 1.7 (range 0-3). According to the Broberg-Morrey score, there were 7 excellent, 9 good, 2 fair, and 0 poor results (with good or excellent results in 89%). Mayo elbow performance score and the disabilities of the arm, shoulder, and hand score were significantly improved postoperatively.The present study demonstrates that arthroscopic fixation of Mason type II radial head fractures using K-wires provided a stable fixation with good clinical outcomes and patient satisfaction.


Androgen-binding protein is co-expressed with oxytocin in the male reproductive tract.
Androgen-binding protein (ABP) and the posterior lobe hormone oxytocin (OT) were co-localized in male rat reproductive organs. Immunostaining of serial semi-thin sections revealed a high rate of coexistence of both antigens in Sertoli cells and in the epithelial cells of the prostate. There was a considerably less co-localization of OT and ABP in epithelial cells of the epididymis, and in the different tissues of the ductus deferens. In situ hybridization with synthetic oligonucleotides complementary to a fragment of ABP mRNA showed specific staining in the same sites that were immunostained for ABP. ABP was isolated by affinity chromatography from homogenates of testis, epididymis, prostate and the content of the prostate lumen. Identical protein patterns could be shown with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in all samples except for the epididymis indicating that ABP structure is similar in all these tissues. ABP seems to be expressed in specified cells throughout the male rat reproductive tract. Most of these cells appear to be oxytocinergic. ABP and OT have previously been detected in the ejaculate. The observed epithelial cells are likely to be their source.


Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway.
Mitochondrial fission plays a role in cardiovascular calcification. Melatonin has previously been shown to protect against cardiovascular disease, so this study sought to explore whether it attenuates vascular calcification by regulating mitochondrial fission via the AMP-activated protein kinase/dynamin-related protein 1 (AMPK/Drp1) signalling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), Drp1 and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were down-regulated, Drp1 was reduced in response to melatonin, and this was accompanied by decreased apoptosis. Melatonin also reduced levels of mitochondrial superoxide, reversed β-glycerophosphate (β-GP)-induced ΔΨm dissipation and decreased mitochondrial fragmentation. The effects of melatonin in β-GP-treated VSMCs were similar to those of mitochondrial division inhibitor 1. Melatonin significantly activated the expression of AMPK and decreased Drp1 expression. Treatment with compound C ablated the observed benefits of melatonin treatment. These findings indicate that melatonin protects VSMCs against calcification by inhibiting mitochondrial fission via the AMPK/Drp1 pathway.


X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED): A Case Report and Overview of the Diagnosis and Multidisciplinary Modality Treatments.
Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by a mutation in either the ectodysplasin (EDA), ectodysplasin A receptor (EDAR), EDAR associated via death domain (EDARADD), or Wnt family member 10A (WNT10A) genes that result in impaired development of ectodermal-derived structures. The literature defines two types of ectodermal dysplasia, which are hypohidrotic and hidrotic. X-linked hypohidrotic ectodermal dysplasia (XLHED), also known as Christ-Siemens-Touraine syndrome, is the most common form and is a variant of ectodermal dysplasia characterized by a classical triad of hypo/adontia, hypohidrosis, and hypotrichosis; whereas, hidrotic type of ectodermal dysplasia, also known as Clouston syndrome, is characterized by a triad of onychodysplasia, hypotrichosis, and palmoplantar hyperkeratosis while sparing the sweat glands. Symptoms of XLHED can begin early in life between the ages of one month to 23 months. XLHED is more commonly seen in males due to the x-linked characteristics of the gene mutations. This disease can be diagnosed by physical exam alone, or in combination with molecular genetic testing. XLHED specifically has an estimated occurrence of one in every 20,000 newborns worldwide. Approximately 5,000 people in the United States have the disease. In this case report, we present an adult patient diagnosed with XLHED. Our objective is to emphasize the significance of early diagnosis, advocate for a multidisciplinary management approach, and shed light on the potential of recombinant protein and targeted gene therapy for further research. By raising awareness of this condition, we aim to improve patient outcomes not only in newborns but also in adults who have already been diagnosed with XLHED.


Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions.
The authors sought to determine the effect of concomitant peroral (PO) administration of cyclosporine (CsA) and sirolimus (SRL, rapamycin) on the tissue distributions of CsA and SRL in the rat. Groups of four adult male Wistar-Furth rats were treated for 14 days with 2.5, 5.0, or 10.0 mg CsA/kg x day. Other groups of four adult male Wistar-Furth rats were treated for 14 days with a 1-to-6.25 weight-to-weight ratio of SRL to CsA at SRL doses of 0.4, 0.8, or 1.6 mg/kg x day. Concentrations of CsA and SRL in homogenates of heart, intestinal, kidney, liver, lung, muscle, spleen, and testes were compared to those in whole blood (WB). There was a large, dose-dependent, distinctive distribution of CsA among rat tissues, as has previously been well documented. At a constant molar dose ratio, concomitant oral administration of SRL produced an approximately two-fold increase in the concentrations of CsA in rat tissues, although SRL did not change the CsA tissue-to-WB partition coefficients. Concomitant oral CsA administration produced dose-dependent increases in SRL tissue concentrations and decreases in the SRL tissue-to-WB partition coefficients. The increases in tissue and WB concentrations on coadministration of both agents may be explained either by an increase in absorption caused by competition between the two agents for binding sites on P-glycoprotein in the gut, a reduced rate of metabolism, or to an as yet unidentified elimination mechanism. The dose-independent and unchanged CsA tissue-to-WB partition coefficients suggest that SRL does not affect the equilibrium of CsA between the central and tissue compartments, namely the tissue uptake or intracellular binding. Altered values of the SRL tissue-to-WB partition coefficients suggest that, under the conditions studied, CsA disturbs the equilibrium of SRL between the central and tissue compartments.


Effect of curcumin on LDL oxidation in vitro, and lipid peroxidation and antioxidant enzymes in cholesterol fed rabbits.
In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS0(4), indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet.


Dynamic MRI in the diagnosis and post surgical evaluation of wandering spleen.
Wandering spleen is a rare but potentially clinically significant entity, and may be a cause for a patient presenting with acute abdomen. Because wandering spleen may present with non-specific symptoms and presentation, it can be a difficult diagnosis to make clinically. This paper describes a case report of the use of dynamic Magnetic Resonance Imaging (MRI) in a young woman to confirm the diagnosis of wandering spleen pre-operatively. The patient underwent a splenopexy and a post-operative MRI confirmed the successful surgical fixation of the patient's spleen.


Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children.
This article reviews 41 studies of the effects of prophylactic CNS treatment on the neurobehavioral development of children with cancer. This research is classified according to studies of (a) children in treatment; (b) long-term survivors; and (c) longitudinal follow-ups of children from the time of diagnosis. Studies vary considerably in design, sample, and outcome variables, so firm conclusions regarding the morbidity of CNS prophylaxis are not currently possible. However, the studies do suggest that CNS prophylaxis does impair cognitive development, particularly when cranial radiation therapy is part of the treatment. There is also evidence of greater impairment in younger children and some suggestion of more frequent impairment of non-language skills relative to language skills. The possible relationships among age, radiation, and non-language cognitive skills may be linked to disruption of white matter CNS structures apparent on autopsy and cerebral tomography following treatment.


Aryl Hydrocarbon Receptor Deficiency Attenuates Oxidative Stress-Related Mesangial Cell Activation and Macrophage Infiltration and Extracellular Matrix Accumulation in Diabetic Nephropathy.
Activation of glomerular mesangial cells (MCs) and functional changes of renal tubular cells are due to metabolic abnormalities, oxidative stress, and matrix accumulation in the diabetic nephropathy (DN). Aryl hydrocarbon receptor (AhR) activation has been implicated in DN. In this study, we investigated the role of AhR in the pathophysiological processes of DN using AhR knockout (AhRKO) and pharmacological inhibitor α-naphthoflavone mouse models. The increased blood glucose, glucose intolerance, MC activation, macrophage infiltration, and extracellular matrix (ECM) accumulation were significantly attenuated in AhRKO mice with diabetic inducer streptozotocin (STZ) treatment. AhR deficiency by genetic knockout or pharmacological inhibition also decreased the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), lipid peroxidation, oxidative stress, NADPH oxidase activity, and N-ɛ-carboxymethyllysine (CML, a major advanced glycation end product) in STZ-induced diabetic mice. CML showed remarkably increased AhR/COX-2 DNA-binding activity, protein-DNA interactions, gene regulation, and ECM formation in MCs and renal proximal tubular cells, which could be reversed by siRNA-AhR transfection. CML-increased AhR nuclear translocation and biological activity in MCs and renal proximal tubular cells could also be effectively attenuated by antioxidants. We elucidate for the first time that AhR plays an important role in MC activation, macrophage infiltration, and ECM accumulation in DN conferred by oxidative stress. AhR-regulated COX-2/PGE2 expression and ECM deposition through oxidative stress cascade is involved in the CML-triggered MC activation and macrophage infiltration. These findings suggest new insights into the development of therapeutic approaches to reduce diabetic microvascular complications. Antioxid. Redox Signal. 24, 217-231.


Brief review: Cardiac complications and platelet activation in COVID-19 infection.
COVID-19 pneumonia, much like that of bacterial and viral community-acquired pneumonia before it, is accompanied by a high rate of cardio- and cerebrovascular events that are associated with an increased risk of complications and a greater mortality. Although the mechanisms underlying the pathogenesis of these adverse events are not entirely clear and may be multifactorial, platelets appear to have a prominent aetiologic role and this, together with an overview of the clinical evidence, forms the basis of this short review.


Nucleotide sequences of chloroplast 5S ribosomal RNA from cell suspension cultures of the liverworts Marchantia polymorpha and Jungermannia subulata.
The nucleotide sequences of chloroplast 5S rRNAs from cell suspension cultures of the liverworts Marchantia polymorpha and Jungermannia subulata were determined. Their nucleotide sequences, 119 nucleotides long, were highly homologous to each other (96% identity) and had high homology with those from chloroplast 5S rRNAs of two higher plants, tobacco (92% identity) and spinach (92-91% identity), but less homology (87-85% identity) with that from a lower plant, the fern Dryopteris acuminata.


Leukodystrophy in patients with ovarian dysgenesis.
We describe clinical, biochemical, pathological, and spectroscopic findings in 4 women, aged 15 to 29 years, from three unrelated families who had a unique combination of a central nervous system white matter disease and primary ovarian failure. All had normal initial development but 3 had borderline low IQ and academic difficulties in primary school. Puberty did not develop in 2 patients and was arrested in a third patient. The fourth patient had premature ovarian failure at the age of 13 years. Head magnetic resonance imaging showed diffuse white matter disease, with frontal cortical atrophy in the most clinically advanced patient. All patients had normal karyotype and normal findings on extensive evaluations for known leukodystrophies, for other metabolic diseases, and for causes of ovarian failure. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in the affected white matter in all patients and reduction of N-acetylaspartate in the unaffected frontal white matter of 2 patients. All patients had evidence of primary gonadal insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on brain biopsy in another patient. In conclusion, we present a novel group of patients who have in common leukodystrophy, primary ovarian dysfunction, and magnetic resonance spectroscopic abnormalities.


Analysis of masseter deformation patterns during a maximum exertion clenching in patients with unilateral chewing.
The aim of the following study is to examine both masseter muscles (left/right) in a group of patients suffering from unilateral chewing during a maximum exertion isometric contraction using the deformation pattern analysis of ultrasound videos and compare them with the results obtained by studying patients with alternate bilateral chewing patterns. This study has been conducted by use of an ultrasound machine and a linear probe which allowed us to record a video (DCM) comprised of 45 frames per second (MicrUs ext-1H Telemed Medical Systems Milano) and a linear probe (L12-5l40S-3 5-12 MHz 40 mm). The probe was fixed to a brace and the patients were asked to clench their teeth as hard as possible, obtain the muscle's maximum exertion, for 5 seconds three times, with 30 seconds intervals in between. Both right and left masseter muscles were analyzed. We applied to the ultrasound video a dedicated software (Mudy 188.8.131.52 AMID Sulmona Italy) for the analysis of muscle deformation patterns. The total number of patients for this study is 150. Out of this number, 50 belong to Group A, mono lateral chewing on the left side arch, and 50 to Group B, mono lateral chewing on the right side arch. The remains patients belong to Group C, bilateral alternate chewing. The deformation pattern analysis of the skeletal muscles on ultrasound videos allows us to highlight with ease the clear difference in the clenching capabilities and strain management between the dominant masseter and the subordinate masseter in a unilaterally chewing patient. In the sample investigated both in Group A and Group B the unilateral chewing is associated with a series of parameters (number, shape, volume, position and orientation of the teeth) and is also associated with the extension of the cutting surface really available.


[Analysis of chromosome aberrations in peripheral blood lymphocyte of medical radiation workers in a tertiary hospital].
Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.


The genome sequence of the Eurasian red squirrel, Sciurus vulgaris Linnaeus 1758.
We present a genome assembly from an individual male Sciurus vulgaris (the Eurasian red squirrel; Vertebrata; Mammalia; Eutheria; Rodentia; Sciuridae). The genome sequence is 2.88 gigabases in span. The majority of the assembly is scaffolded into 21 chromosomal-level scaffolds, with both X and Y sex chromosomes assembled.


Fertility decline in Prussia: estimating influences on supply, demand, and degree of control.
Change in marital fertility in 407 Prussian Kreise from 1875 to 1910 is modeled to depend on the gap between the number of desired surviving births, N*, divided by child survival, s, and the number that would be born under natural marital fertility, M, given the age at marriage. Some fraction of this gap is averted, depending on the propensity to avert unwanted births, D. Although none of these components is observed directly, we can estimate each indirectly under strong assumptions. Decline in N*/s accounts for twice as much of the decline in fertility as does an increase in D. Natural fertility rose during the period. Unwanted births increased slightly, despite a tripling of births averted. The most important causes of decline in N* were increases in female labor supply, real income, and health workers. A rising level of education is the most important cause of increasing propensity to avert births. Demand-side changes were important causes of the transition, but changes in readiness to contracept also were important, as was the interaction of the two.


Study on the Interactive Factors between Physical Exercise and Mental Health Promotion of Teenagers.
Adolescence is a key period of growth in life, and the psychological development of teenagers in this period is in a stage of rapid maturity without maturity, with distinct characteristics of self-contradiction. People's in-depth understanding of the concept of mental health has prompted people to have a new understanding of the function of physical exercise, trying to make an in-depth study of the function of physical exercise. Teenagers are considered to be the main force for the future development of our society, so in the process of educating teenagers, we should not only pay attention to the exercise of physical quality but also pay attention to the education of psychological quality. With the rapid development of modern society and science and technology, human life is becoming more and more prosperous, and people have to face various conflicts and troubles. The faster pace of life makes people face more pressure. In this paper, the interaction between adolescent physical exercise and mental health factors is discussed, and the promotion effect of physical exercise on college students' mental health is analyzed, so as to provide theoretical basis for further improving adolescent mental health.


Alcohol consumption among pregnant and childbearing-aged women--United States, 1991 and 1995.
Moderate to heavy alcohol use by women during pregnancy has been associated with many severe adverse effects in their children, including fetal alcohol syndrome (FAS)--with facial dysmorphology, growth retardation, and central nervous system deficits--and other neurodevelopmental effects. Early prenatal alcohol exposure can occur unintentionally (i.e., before a woman knows she is pregnant); in addition, women who drink at high levels before pregnancy are at increased risk for drinking during pregnancy. Ongoing surveillance for alcohol consumption among pregnant and childbearing-aged women is important for monitoring the impact of efforts to prevent this risk behavior. This report analyzes and compares data from the 1995 Behavioral Risk Factor Surveillance System (BRFSS) and previously reported 1991 BRFSS data for women aged 18-44 years, and presents the prevalence of alcohol consumption among pregnant women and overall and state-specific prevalence rates among women of childbearing age. The findings indicate a substantial increase in alcohol use among pregnant women from 1991 to 1995.


Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations--many questions, some answers.
Nanomaterials display novel properties to which most toxicologists have not consciously been exposed before the advent of their practical use. The same properties, small size and particular shape, large surface area and surface activity, which make nanomaterials attractive in many applications, may contribute to their toxicological profile. This review describes what is known about genotoxicity investigations on nanomaterials published in the openly available scientific literature to-date. The most frequently used test was the Comet assay: 19 studies, 14 with positive outcome. The second most frequently used test was the micronucleus test: 14 studies, 12 of them with positive outcome. The Ames test, popular with other materials, was less frequently used (6 studies) and was almost always negative, the bacterial cell wall possibly being a barrier for many nanomaterials. Recommendations for improvements emerging from analyzing the reports summarized in this review are: Know what nanomaterial has been tested (and in what form); Consider uptake and distribution of the nanomaterial; Use standardized methods; Recognize that nanomaterials are not all the same; Use in vivo studies to correlate in vitro results; Take nanomaterials specific properties into account; Learn about the mechanism of nanomaterials genotoxic effects. It is concluded that experiences with other, non-nano, substances (molecules and larger particles) taught us that mechanisms of genotoxic effects can be diverse and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus a practical, pragmatic approach is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands adaptations and the interpretation of results from the genotoxicity tests may need additional considerations. This review should help to improve standard genotoxicity testing as well as investigations on the underlying mechanism and the interpretation of genotoxicity data on nanomaterials.


Seasonal and habitat-related distribution pattern of Synechococcus genotypes in Lake Constance.
The abundance and distribution of Synechococcus spp. in the autotrophic picoplankton of Lake Constance, were followed in the pelagic and littoral habitat by qPCR over 2 years. One genotype, represented by isolated phycoerythrin-rich strain BO 8807, showed a seasonal distribution pattern in both habitats. Before a stable thermal stratification, the maximum of both the Synechococcus population and genotype BO 8807 occurred at 15 or 20 m water depth in the pelagic habitat. During the summer stratification, when the absolute abundance of all Synechococcus spp. was highest above 15 m, the absolute and relative abundance of genotype BO 8807 was maximal at 20 m. These results indicate that Synechococcus spp. or single genotypes are present in deep maxima in Lake Constance. The in situ dynamics of genotype BO 8807 is consistent with the observation that isolated strain BO 8807 requires higher phosphate concentrations for maximum growth rates than a strain from the same phylogenetic cluster that dominates the pelagic summer population. In contrast to these findings, low genome numbers of phycocyanin-rich genotype BO 8805 were found temporarily only in both the littoral and pelagic plankton. Microscopy revealed that PC-rich cells in general occurred preferentially in the littoral habitat. We discuss our results with respect to the versatility of picocyanobacteria of the evolutionary lineage VI of cyanobacteria, and a habitat-related distribution pattern of Synechococcus genotypes.


Viral DNA integration and methylation of human papillomavirus type 16 in high-grade oral epithelial dysplasia and head and neck squamous cell carcinoma.
This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED (N = 19) and HNSCC (N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 (p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.


The role of logistic constraints in termite construction of chambers and tunnels.
In previous models of the building behaviour of termites, physical and logistic constraints that limit the movement of termites and pheromones have been neglected. Here, we present an individual-based model of termite construction that includes idealized constraints on the diffusion of pheromones, the movement of termites, and the integrity of the architecture that they construct. The model allows us to explore the extent to which the results of previous idealized models (typically realised in one or two dimensions via a set of coupled partial differential equations) generalize to a physical, 3-D environment. Moreover we are able to investigate new processes and architectures that rely upon these features. We explore the role of stigmergic recruitment in pillar formation, wall building, and the construction of royal chambers, tunnels and intersections. In addition, for the first time, we demonstrate the way in which the physicality of partially built structures can help termites to achieve efficient tunnel structures and to establish and maintain entrances in royal chambers. As such we show that, in at least some cases, logistic constraints can be important or even necessary in order for termites to achieve efficient, effective constructions.


High free triiodothyronine, and free-triiodothyronine-to-free-thyroxine ratio are associated with metabolic syndrome in a euthyroid employee population: the Zhejiang Zhenhai study.
The aim of this study was to elaborate the link of thyroid hormones (THs) and metabolic syndrome (MetS) in a Chinese euthyroid employee population with MetS component(s). An annual health checkup was performed on employees in 2019. Anthropometric parameters, metabolic parameters, and thyroid function were measured. A questionnaire was used in conjunction with Zhenhai Lianhua Hospital database to receive employees' medication records and thyroid surgical history records. A total of 5486 eligible employees were included; the prevalence of MetS was generally higher in males than in females (38.9 vs. 30.4%, P < 0.001). Among employees with central obesity, hypertriglyceridemia, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), the prevalence of MetS was 68.8, 63.6, 68.2, 48.8, and 60.0% in males and 72.6, 63.3, 61.3, 42.3, and 42.3% in females, respectively. Logistic regression analysis showed that thyroid-stimulating hormone and free thyroxine (FT4) quartiles had no significant impact on MetS. Free triiodothyronine/free thyroxine (FT3/FT4) and free triiodothyronine (FT3)) quartiles were positively associated with the increased odds ratio (OR) for MetS and dyslipidemia (hypertriglyceridemia and low HDL-C), regardless of gender. In males, FT3 and FT3/FT4 quartiles were positively associated with the OR for central obesity, whereas FT4 quartiles were negatively associated; both FT3 and FT4 quartiles were positively associated with increased OR of hyperglycemia, while similar results were not observed in females. Interaction analysis indicated no significant effect of gender and TH interactions on risk of MetS. High FT3 and FT3/FT4 were strongly linked with MetS and dyslipidemia in our study, even in the euthyroid individuals. Tighter control of thyroid function was necessary for those with preexisting MetS component(s).


Niraparib for the treatment of ovarian cancer.
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic. Future directions plus ongoing trials, including novel combinations are highlighted. Expert opinion: There is now level 1 evidence of efficacy from the first randomized placebo-controlled phase III trial using niraparib maintenance in women with platinum-sensitive recurrent HGSOC with complete or partial response post platinum-based chemotherapy. Niraparib improved progression free survival over placebo in all groups of women. The benefit was greatest in patients with germline BRCA1/2 mutation, followed by HRD positive tumors; however, absence of either does not exclude the possibility of benefit from niraparib maintenance. Additional studies are underway with niraparib in the first line maintenance, and 4th/5th line recurrence treatment settings.


Preparation and properties of biomedical porous titanium alloys by gelcasting.
Porous titanium alloys have been prepared by gelcasting in this study. The elastic solid green body was first polymerized and then vacuum sintered to porous titanium alloys with low contamination by controlling sintering conditions. The microstructure and the total porosity of the vacuum sintered porous Ti-Co and Ti-Mo alloys were analyzed by using scanning electron microscopy and x-ray diffraction. Moreover, compression and bending tests were conducted to investigate their mechanical properties. The results show that open and closed three-dimensional pore morphologies and total porosity ranging from 38.34% to 58.32% can be achieved. In contrast to porous Ti by gelcasting, the compression and bending strengths of porous titanium alloys were significantly increased by adding Mo and Co with Young's modulus ranging between 7-25 GPa, which is close to that of human cortical bone, therefore being suited for potential application in load-bearing implants.


Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States.
Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2. States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted. A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel. Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.


Sirolimus-associated hepatotoxicity in the kidney graft recipient.
The aim of our paper was to describe hepatotoxicity of sirolimus (SRL) in a kidney graft recipient. We report the case of a 30-year-old male after kidney transplantation, treated with steroids, cyclosporin A and SRL, with steroid-resistant acute rejection in anamnesis. At 16th month after transplantation, elevation of serum aminotransfereases was observed. After exclusion of common reasons of this condition, liver biopsy was performed. Nonspecific changes were observed, with probability of drug-induced injury. SRL was changed to mycophenolate mofetil, which was followed by quick normalization of serum aminotransferase levels. Hepatoxicity is a rare complication of SRL therapy and may be connected with some diagnostic and/or therapeutic problems. Conversion to another immunosuppressant seems to be an appropriate procedure in this condition.


Semimetal/semiconductor nanocomposites for thermoelectrics.
In this work, we present research on semimetal-semiconductor nanocomposites grown by molecular beam epitaxy (MBE) for thermoelectric applications. We study several different III-V semiconductors embedded with semimetallic rare earth-group V (RE-V) compounds, but focus is given here to ErSb:In(x)Ga(1−x)Sb as a promising p-type thermoelectric material. Nanostructures of RE-V compounds are formed and embedded within the III-V semiconductor matrix. By co-doping the nanocomposites with the appropriate dopants, both n-type and p-type materials have been made for thermoelectric applications. The thermoelectric properties have been engineered for enhanced thermoelectric device performance. Segmented thermoelectric power generator modules using 50 μ m thick Er-containing nanocomposites have been fabricated and measured. Research on different rare earth elements for thermoelectrics is discussed.


Conjugated organometallic polymer containing a redox-active center.
The new conjugated organometallic polymer (-spacer-C[triple bond]C-Pt(PBu3)2-C[triple bond]C-)n (3; spacer = para-bis(diphenyl(tetramethyl)quinone diimine) and the cyclic mononuclear model complex, spacer'-C[triple bond]C-Pt(PEt3)2-C[triple bond]C x CuCl (4; spacer' = ortho-diphenyl-2,3,5,6-tetramethyl-1,4-benzoquinone diimine) were synthesized from the 1:1 condensation of the corresponding diethynyl ligands (2-para and 2-ortho (para- and ortho-diethynyl-diphenyl-2,3,5,6-tetramethylquinone diimine), respectively), with the trans-Pt(PBu3)2Cl2 for polymer 3 and cis-Pt(PEt3)2Cl2 for 4. The materials were characterized by GPC, DSC, ATG, and electrochemistry for polymer 3, and by X-ray diffraction for 4. Polymer 3 exhibits a M(n) of 18500, M(w) of 25000 with a PD of 1.37. The trans-geometry about Pt in polymer 3 was confirmed by 31P NMR and IR/Raman spectroscopy. The cyclic voltammogram study on the model complex trans-Pt(PBu3)2(C[triple bond]CPh)2, spacer 1-para (Me3Si-C[triple bond]C-R-C[triple bond]C-SiMe3; R = para-diphenyl-2,3,5,6-tetramethyl-1,4-benzoquinone diimine) and polymer 3 demonstrated that polymer 3 in the presence of trifluoroacetic acid (TFA) exhibits a quasi reversible 2-electron reduction process centered at 0.48 V versus SCE corresponding to the reduction of the protonated quinone diimine unit into the corresponding diamine. The UV-vis spectra of the spacer 2-para (440 nm) and polymer 3 (502 nm) are characterized by red-shifted charge transfer (CT) absorptions (C6H4C[triple bond]C --> quinone diimine for 2-para; and (C6H4C[triple bond]C)2Pt --> quinone diimine for polymer 3). These assignments are corroborated by density-functional theory (DFT) and time-dependent density-functional theory (TDDFT) computations. Polymer 3 is not luminescent in the solid state or in solution at 77 K and 298 K.


Transjugular intrahepatic portosystemic stent-shunt after orthotopic liver transplantation in a patient with early recurrence of portal hypertension of unknown origin.
A 65-year-old italian patient developed complicated portal hypertension immediately after orthtopic liver transplantation (OLT) necessitating shunt creation. One to five weeks after OLT, massive ascitic fluid losses of up to 121/day developed. Vascular and major hepatic-parenchymal abnormalities were excluded by duplexsonography, angiography and initial histology, respectively. A peritoneovenous shunt (Denver-shunt) on day 31 after OLT reduced (by about 50%) but did not stop ascitic fluid losses. Furthermore, three variceal bleedings occurred after implantation of the Denver-shunt. Direct portography on day 45 after OLT revealed portal hypertension (pressure gradient of 26 mmHg) requiring the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPS) leading to a reduction of the pressure gradient to 13 mmHg. Subsequently, ascites resolved within ten days and esophageal varices improved. Liver function parameters normalized inspite of recurrence of HCV infection with detection of HCV RNA in serum already in the fifth week after OLT. During follow-up, histological findings deteriorated from mild changes to extended fibrosis at day 61 after OLT, which might have contributed to the maintenance of portal hypertension. The deterioration of liver histology was accompanied by an improvement/normalization of liver graft function. There was no evidence for additional viral liver infections, e.g. hepatitis B or cytomegalovirus infection. This case illustrates an etiologically unclear syndrome developing directly after OLT and reaffirms the effectiveness of TIPS in the treatment of complicated portal hypertension even after liver transplantation.


Zinc and Cadmium Complexes of Pyridinemethanol Carboxylates: Metal Carboxylate Zwitterions and Metal-Organic Frameworks.
The heterofunctional lactone furo[3,4-b]pyridin-5(7H)-one (L1 ) undergoes a coordination-induced ring-opening reaction with Zn(NO3 )2 ⋅ 6H2 O to yield the zwitterionic [Zn(L1 ')2 (H2 O)2 ] (1, L1 '=2-(hydroxymethyl)nicotinate) with an uncoordinated carboxylate. The same reaction with Cd(NO3 )2 ⋅ 4H2 O provides a two-dimensional (2D) network of [Cd(L1 ')2 ]n (3) with the carboxylates coordinated to cadmium(II) propagating the assembly. The corresponding reactions of Zn(NO3 )2 ⋅ 6H2 O and Cd(NO3 )2 ⋅ 4H2 O with 2-(hydroxymethyl)isonicotinic acid (HL2 ) generated zwitterionic [Zn(L2 )2 (H2 O)2 ] (2) and a 2D network [Cd(L2 )2 ]n ⋅nDMF (4, DMF=N,N'-dimethylformamide), respectively. Complexes 1-4 are weakly emissive, giving ligand-centered emissions at 409 nm (1), 412/436 nm (2), 404 nm (3), and 412/436 nm (4) in CHCl3 solutions upon excitation at 330 nm. This work points to the potential of using 'hidden' functionalities widely found in small organic molecules and natural products for the construction of coordination complexes with new functionality and potential applications.


A novel matrix for hydrophobic interaction chromatography and its application in lysozyme adsorption.
A novel 1-naphthylamine (NA) coupled poly(2-hydroxyethyl methacrylate-co-N-methacryloyl-(L)-histidine methyl ester) [NA-PHEMAH] supermacroporous monolithic hydrophobic cryogel was prepared via covalent coupling of NA to PHEMAH for adsorption of lysozyme from aqueous solution. Firstly, PHEMAH monolithic cryogel was prepared by radical cryocopolymerization of HEMA with MAH as a functional comonomer and N,N'-methylene-bisacrylamide (MBAAm) as a crosslinker directly in a plastic syringe, and then NA molecules were covalently attached to the imidazole rings of MAH groups of the polymeric structure. The prepared, NA-PHEMAH, supermacroporous monolithic hydrophobic cryogel was characterized by scanning electron microscopy (SEM). The effects of initial lysozyme concentration, pH, salt type, temperature and flow rate on the adsorption efficiency of monolithic hydrophobic cryogel were studied in a column system. The maximum amount of lysozyme adsorption from aqueous solution in phosphate buffer was 86.1 mg/g polymer at pH 8.0 with a flow rate of 1 mL/min. It was observed that lysozyme could be repeatedly adsorbed and desorbed with the NA-PHEMAH monolithic hydrophobic cryogel without significant loss of the adsorption capacity.


Pancreatic phospholipase A2: isolation of the human gene and cDNAs from porcine pancreas and human lung.
Oligonucleotide probes synthesized using the published protein sequence for porcine pancreatic phospholipase A2 (PLA2; Puijk et al., 1977), were used to screen a cDNA library made from porcine pancreas. One resulting clone which encoded the entire porcine PLA2 enzyme was then used to screen various human cDNA and gene libraries. A 562-bp cDNA clone from human lung and two overlapping genomic clones encoding the identical transcript were obtained. These clones encoded a 126-residue peptide corresponding to human "pancreatic" PLA2. The gene spanned 4.9 kb and contained three introns of 1692, 800, and about 2650 bases, respectively. Hybridization of the human cDNA against blots of total human DNA detected the same set of fragments contained in both genomic clones and failed to detect more than one distinct gene. Under equivalent conditions, the same probe detected two discrete bands in cobra (Naja naja) genomic DNA. Apparently, there is a single or small number of identical human genes encoding "pancreatic" PLA2 which are transcribed also in lung tissue; human pancreatic PLA2 appeared more closely related at the nucleotide level to snake counterparts than to other reported human PLA2 enzyme forms.


Nanoparticle-Mediated Mechanical Destruction of Cell Membranes: A Coarse-Grained Molecular Dynamics Study.
The effects of binding mode, shape, binding strength, and rotational speed of actively rotating nanoparticles on the integrity of cell membranes have been systematically studied using dissipative particle dynamics simulations. With theoretical analyses of lipid density, surface tension, stress distribution, and water permeation, we demonstrate that the rotation of nanoparticles can provide a strong driving force for membrane rupture. The results show that nanoparticles embedded inside a cell membrane via endocytosis are more capable of producing large membrane deformations under active rotation than nanoparticles attached on the cell membrane surface. Nanoparticles with anisotropic shapes produce larger deformation and have a higher rupture efficiency than those with symmetric shapes. Our findings provide useful design guidelines for a general strategy based on utilizing mechanical forces to rupture cell membranes and therefore destroy the integrity of cells.


Increased serum and cerebrospinal fluid FGF-2 levels in amyotrophic lateral sclerosis.
Lack of growth factors and hypoxia are two recent hypotheses about mechanisms underlying motor neuron death in amyotrophic lateral sclerosis. With this background, serum from 15 patients with amyotrophic lateral sclerosis and 15 controls, and CSF from 15 patients and 10 controls were analysed for fibroblast growth factor 2 (FGF-2) using an immunoassay. Serum FGF-2 levels were higher in the patient group than in the control group. FGF-2 was detected in CSF in 11/15 patients, but in none of the 10 control subjects. There were no correlations between age, duration of disease or clinical rating and FGF-2 levels. The findings indicate that FGF-2 is involved in the pathophysiological chain of events in this disorder.


Prostate cancer patients gradually advance goals for rehabilitation after radical prostatectomy: applying a lines-of-defense model to rehabilitation.
Following tumor surgery, urinary incontinence challenges prostate cancer patients' functional health. Adjustments of functional goals (lines of defense [LoDs]) were examined during rehabilitation from incontinence. A conceptual model proposing stepwise and distinct upward adjustments of LoDs, ranging from minimizing discomfort (lowest LoD) to protecting self-reliance (highest LoD), was investigated. Within 7 months following the onset of incontinence, 175 patients completed questionnaires at 4 occasions. A theory-based hierarchy was imposed on time-invariant latent classes of LoD-endorsements. As incontinence receded, patients transitioned upward through the hierarchy of LoD-classes, matched LoDs to concurrent incontinence levels, and thus promptly claimed independent functioning with physical improvements.


"It's Like a Phantom Disease": Patient Perspectives on Access to Treatment for Chagas Disease in the United States.
Chagas disease (CD) affects > 6 million people globally, including > 300,000 in the United States. Although early detection and etiological treatment prevents chronic complications from CD, < 1% of U.S. cases have been diagnosed and treated. This study explores access to etiological treatment from the perspective of patients with CD. In semi-structured interviews with 50 Latin American-born patients of the Center of Excellence for Chagas Disease at the Olive View-UCLA Medical Center, we collected demographic information and asked patients about their experiences managing the disease and accessing treatment. Patients were highly marginalized, with 63.4% living below the U.S. poverty line, 60% lacking a high school education, and only 12% with private insurance coverage. The main barriers to accessing health care for CD were lack of providers, precarious insurance coverage, low provider awareness, transportation difficulties, and limited time off. Increasing access to diagnosis and treatment will not only require a dramatic increase in provider and public education, but also development of programs which are financially, linguistically, politically, and geographically accessible to patients.


Inhibition of multiple voltage-gated calcium channels may contribute to spinally mediated analgesia by epipregnanolone in a rat model of surgical paw incision.
Voltage-activated calcium channels play an important role in excitability of sensory nociceptive neurons in acute and chronic pain models. We have previously shown that low-voltage-activated calcium channels, or T-type channels (T-channels), increase excitability of sensory neurons after surgical incision in rats. We have also found that endogenous 5β-reduced neuroactive steroid epipregnanolone [(3β,5β)-3-hydroxypregnan-20-one] blocked isolated T-currents in dorsal root ganglion (DRG) cells in vitro, and reduced nociceptive behavior in vivo, after local intraplantar application into the foot pads of heathy rats and mice. Here, we investigated if epipregnanolone exerts an antinociceptive effect after intrathecal (i.t.) application in healthy rats, as well as an antihyperalgesic effect in a postsurgical pain model. We also studied if this endogenous neurosteroid blocks currents originating from high voltage-activated (HVA) calcium channels in rat sensory neurons. In in vivo studies, we found that epipregnanolone alleviated thermal and mechanical nociception in healthy rats after i.t. administration without affecting their sensory-motor abilities. Furthermore, epipregnanolone effectively reduced mechanical hyperalgesia after i.t application in rats after surgery. In subsequent in vitro studies, we found that epipregnanolone blocked isolated HVA currents in nociceptive sensory neurons with an IC50 of 3.3 μM in a G-protein-dependent fashion. We conclude that neurosteroids that have combined inhibitory effects on T-type and HVA calcium currents may be suitable for development of novel pain therapies during the perioperative period.


Noise as an informational cue for decision-making: the sound of rain delays bat emergence.
Background noise can have strong negative consequences for animals, reducing individual fitness by masking communication signals, impeding prey detection and increasing predation risk. While the negative impacts of noise across taxa have been well documented, the use of noise as an informational cue, providing animals with reliable information on environmental conditions, has been less well studied. In the tropical rainforest, downpours can be intense and frequent. Strong rainfall may impede efficient orientation and foraging for bats that need echolocation to both navigate and detect prey, and can result in higher flight costs due to increased metabolic rates. Using playback experiments at natural roosts, we tested whether two bat species, differing in their hunting strategies and foraging habitats, use rain noise as a cue to delay emergence from their roosts. We found that both species significantly delayed their emergence time during rain noise playbacks versus silence and ambient noise controls. We conclude that bats can use background noise, here the acoustic component of rainfall, as a reliable informational cue to make informed decisions, in this case about whether to initiate foraging trips or remain in the shelter of their roosts. Our findings suggest that environmental background noise can sometimes be beneficial to animals, in particular in situations where other sensory cues may be absent.


Social networks and voter turnout.
This paper develops a model of voter turnout that embeds Riker and Ordeshook's (1968 Am. Pol. Sci. Rev. 62, 25-42 (doi:10.2307/1953324)) calculus of voting into the context of a social network. In the model, an individual's expressive benefits to voting depend on the behaviour of their social contacts. We show that there may be multiple equilibria and analyse how these equilibria depend on the structure of the network. We discuss six empirical implications of the model for turnout, some of which suggest novel answers to longstanding puzzles in the turnout literature, such as: why are higher income individuals more likely to vote even in cases when registration costs are low? Why is turnout so difficult to predict? Why does lowering registration costs disproportionately increase turnout among high-income voters? And why do we observe inertia in turnout across elections?


Association of cancer history with Alzheimer's disease onset and structural brain changes.
Epidemiological studies show a reciprocal inverse association between cancer and Alzheimer's disease (AD). The common mechanistic theory for this effect posits that cells have an innate tendency toward apoptotic or survival pathways, translating to increased risk for either neurodegeneration or cancer. However, it has been shown that cancer patients experience cognitive dysfunction pre- and post-treatment as well as alterations in cerebral gray matter density (GMD) on MRI. To further investigate these issues, we analyzed the association between cancer history (CA±) and age of AD onset, and the relationship between GMD and CA± status across diagnostic groups in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort study. Data was analyzed from 1609 participants with information on baseline cancer history and AD diagnosis, age of AD onset, and baseline MRI scans. Participants were CA+ (N = 503) and CA- (N = 1106) diagnosed with AD, mild cognitive impairment (MCI), significant memory concerns (SMC), and cognitively normal older adults. As in previous studies, CA+ was inversely associated with AD at baseline (P = 0.025); interestingly, this effect appears to be driven by non-melanoma skin cancer (NMSC), the largest cancer category in this study (P = 0.001). CA+ was also associated with later age of AD onset (P < 0.001), independent of apolipoprotein E (APOE) ε4 allele status, and individuals with two prior cancers had later mean age of AD onset than those with one or no prior cancer (P < 0.001), suggesting an additive effect. Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA- across diagnostic groups (P crit < 0.001, uncorrected); this cluster of lower GMD appeared to be driven by history of invasive cancer types, rather than skin cancer. Thus, while cancer history is associated with a measurable delay in AD onset independent of APOE ε4, the underlying mechanism does not appear to be cancer-related preservation of GMD.


[Hygiene and health importance of histamine as an unhealthy factor in several food products].
Epidemiologic reports on food-borne diseases from different countries show not infrequently outbreaks due to histamine toxicity. The Authors were interested in assessing the relative importance of this nosological entity in Italy and made a global review of old and recent literature on the subject referring also their earliest data on a recently performed laboratory work. Several foods can show histamine contents potentially toxic for man; amongst the most frequently incriminated products fish, especially the scombroid species (tuna, mackerel), plays a pre-eminent role in the etiology of the so called scombrotoxic fish poisoning. This syndrome begins from a few minutes to two hours from incriminated meals and presents itself with the characteristic signs and symptoms of histamine activity on various organs and is very rarely, if ever, life threatening. Histamine formation in food is due to the decarboxylase activity of some microorganisms, mainly enterobacteria; they can be part of its normal flora or represent a secondary contamination and find a favourable environment for outgrowth if food is not stored or processed in proper conditions. An international outlook on the epidemiology of this syndrome is then given, including some considerations on the real dimension of the problem in Italy, at present widely underestimated. Though a pioneer work was accomplished by Pergola, who started his researches in 1910 after receiving several reports of food poisoning related to consumption of tuna and finally established the causative role of histamine, we are lacking at present an up to date picture of this problem in our country, notwithstanding a few sporadic notifications. Two of the most relevant ones concern a survey in Rome on a collection of 110 cases observed in the seventies and an outbreak occurred in Palermo in 1979 affecting nearly 250 people. The relationship between the intake of histamine and the clinical effects on man of a given dose are then evaluated together with histamine catabolic pathways in the gut, where possible interference by enhancing substances may occur. Finally a brief review of the analytical methods currently employed gives the Authors the possibility to refer about their first data of a survey on the hygienic quality of scombroid species commercialized in their metropolitan area.


FDA regulation of technology and surgical devices in the operating room.
Federal regulation of medical devices began in 1976 with the signing of the Medical Device Amendments to the Food, Drug and Cosmetic Act. For the purpose of regulating medical devices, the Food and Drug Administration is divided into various divisions and branches, including the Office of Device Evaluation. The evolution of the Food and Drug Administration's regulations of laparoscopic devices is described. Also described is the technology of laparoscopic surgical devices and how they are regulated by the Office of Device Evaluation. Trends towards the future of laparoscopic devices, and their regulation, are reviewed.


Patterns of failure in squamous cell carcinoma of the vagina treated with definitive radiotherapy alone: what is the appropriate treatment volume?
The purpose of this study was to review treatment results, sites of failure, and complications in relation to the irradiation volume for carcinoma of the vagina treated with radiotherapy alone. A retrospective review of 65 patients with histologically confirmed squamous cell carcinoma of the vagina who received definitive radiotherapy was undertaken. The 5-year cause-specific survival rates were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB, 55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5 years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III, 89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients. Eighty-five percent of pelvis recurrences were in the primary treatment field. Although pelvic control rates were not increased by use of larger treatment fields (>2,700 cm(3)), moderate acute and late effects were increased with these fields. Carcinoma of the vagina appears to have a different failure pattern than carcinoma of the cervix. The primary failure sites are the vagina and the paracolpal tissues and the inguinal nodes. Because of this, the superior edge of the pelvic fields does not have to extend above the bottom of the sacroiliac joints except with advanced lesions.


Effect of p15-associated protease from an avian RNA tumor virus on avian virus-specific polyprotein precursors.
A proteolytic activity is associated with structural protein p15 in avian RNA tumor viruses. Its effect on the known intracellular viral polyprotein precursors obtained by immunoprecipitation was investigated. Cleavage of Pr76gag resulted in the sequential appearance of p15, p27, and p19. The intracellular precursor Pr180gag-pol was also cleaved by p15, whereas the intracellular glycoprotein precursors of avian RNA tumor viruses, Pr92env, remained unaffected by p15 under all conditions tested. The specificities of the antibodies used to precipitate the precursors influenced the pattern of intermediates and cleavage products obtained by p15 treatment. If virus harvested from the the Prague strain of Rous sarcoma virus, subgroup C-transformed cells at 15-min intervals was incubated at 37 degrees C for further maturation, RNA-dependent DNA polymerase activity showed an optimum of DNA synthesis with 70S viral RNA or synthetic template-primers after short incubation periods. The presence of additional p15 during incubation resulted in a shift of the enzyme activity peak toward earlier time points. Virus harvested at 3-h intervals contained significant amounts of Pr180gag-pol and Pr76gag. The addition of p15 resulted in the cleavage of Pr180gag-pol and Pr76gag, but only a few distinct low-molecular-weight polypeptides appeared. Treatment of purified RNA-dependent DNA polymerase with p15 in vitro resulted in a disappearance of the beta subunit and an enrichment of the alpha subunit. In addition, a polypeptide of 32 x 10(3) molecular weight was generated. The cleavage pattern observed differed from the one obtained by trypsin treatment.


Assessment of equivalence of adipose tissue treatment with a noncontact field RF system delivering 200 W for 30 min and 300 W for 20 min: An in vivo porcine study.
Abdominal circumferential reduction with noncontact high frequency apoptosis-inducing field RF (AiRF) is becoming very popular. The present study compared the treatment results from two different sets of parameters giving the same dose from the same system in an in vivo porcine model. Two 10 cm × 10 cm areas were symmetrically marked on both sides of the midline (total of 4 areas) over the rectus abdominis muscle of two anesthetized female micropigs. In Animal A (G1), 27.12 MHz AiRF treatment was given at 200 W for 30 min, and 300 W for 20 min in Animal B (G2). Four sessions were performed at weekly intervals. Gross observation by a veterinary specialist was performed on a daily basis. Temperature measurements (fat and skin), clinical photography and ultrasound imaging were carried out at each session. In addition, blood chemistry was performed before each session to check lipid levels, any adverse changes in markers for liver damage in addition to an enzyme-linked immunosorbent assay (ELISA) for raised levels of TNF-α and IL-1β. Biopsies were taken and routinely processed for hematoxylin and eosin, Toluidine blue and oil red O stains to examine for tissue damage at baseline and after each treatment. TUNEL assays were performed to check of apoptotic-related DNA damage. Follow-up assessments included photography, ultrasound, ELISA tests and biopsies which were taken regularly up to 90 days after the final treatment. The maximum adipose tissue temperatures at and over the apoptotic threshold of 43°C were reached and maintained in both G1 and G2. The skin surface temperature was slightly higher in G2 after 20 min than in G1 after 30 min, but was still below 43°C. Gross and magnified observation revealed no appreciable differences or thermally-mediated damage between the skin of either of the two groups after the treatments or during the 90-day follow-up period. No lasting erythema or any other adverse event was seen in either group. The liver enzyme markers showed very similar patterns over the 4 weeks of treatment compared with baseline with no levels outside of the normal range. Triglycerides were all within normal rage with no significant differences between the groups. Remarkably similar patterns were noted for the ELISAs in both groups performed over the 4 weeks of treatment and at periods during the 90-day follow-up with no notable abnormal changes in levels. Staining patterns for both G1 and G2 specimens were similar for all stain types during treatment and the 90-day follow-up, showing decreased numbers of adipocytes by the 90-day point. The ultrasound findings revealed a 44.8% and 55.6% decrease in the adipose layer for G1 and G2, respectively, at the 90-day assessment. The 200 W AiRF treatment for 30 min (G1) and the 300 W AiRF treatment for 20 min (G2) produced very similar results in the porcine model for all assessments and at all assessment points during and up to 90 days after treatment, with slightly better findings suggested for G2. Based on the above findings, the two different settings, delivering the same dose, produced good results with no skin damage and no adverse events. This has implications in busy clinics for AiRF treatment, where the shorter treatment time could represent time saving for the clinic and the patient without compromising safety and giving equal if not better efficacy.


Determination of PAHs in Solution with a Single Reference Standard by a Combination of 1H Quantitative NMR Spectroscopy and Chromatography.
We have applied a combination of 1H quantitative NMR spectroscopy (1H-qNMR) and chromatography (GC or LC) to establish reliable analytical methods (qNMR/GC and qNMR/LC) for organic compounds. In this method, a reference standard is used as an internal standard for both 1H-qNMR and chromatography to estimate relative molar sensitivity (RMS) for analytes. The RMS values are calculated from the molar ratios between analytes and the reference standard obtained by 1H-qNMR; and the response ratio between them obtained by chromatography. Concentrations of analytes in the organic solution can be simultaneously determined from the RMS and amount of the reference standard added in the sample solution. This analytical method is an innovative one because only one reference standard with International System of Units (SI)-traceable property value, purity, or concentration, is necessary to determine accurate concentrations of multiple organic components in organic solutions, without the respective certified reference standards for various analytes. To verify this method, a certified reference material, NIST SRM 1647f, was used. Among the 16 polycyclic aromatic hydrocarbons (PAHs) included in NIST SRM 1647f, naphthalene and benzo[a]pyrene were selected as analytes for this method, using 1,4-bis(trimethylsilyl)benzene-d4 as the reference standard. Each quantitative value obtained by qNMR/GC and qNMR/LC agreed with each certified value within its expanded uncertainty.


Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer.
Recent discovery of mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma greatly stimulated biomarker research on predictive factors for EGFR tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib. Although patients with activating mutations of the EGFR generally respond to EGFR TKIs very well, it is natural to assume that there is no sole determinant, considering great complexity and redundancy of the EGFR pathway. Subsequently, roles of different types of EGFR mutations or mutations of genes that are members of the EGFR pathway such as KRAS and HER2 have been evaluated. In this review, we summarize the recent findings about how mutations of the EGFR and related genes affect sensitivity to EFGR-TKIs. We also discuss molecular mechanisms of acquired resistance to EGFR-TKIs that is almost inevitable in EGFR-TKI therapy. The door for genotype-based treatment of lung cancer is beginning to open, and through these efforts, it will be possible to slow the progression of lung cancer and eventually, to decrease mortality from lung cancer.


New devices: the McDermott spirometer.
The assessment of a new bellows spirometer against a water spirograph showed: slight alinearity, minimal overestimation of FVC (1.7%) and underestimation of FEV 1-0 (2.9%) as well as of the ratio FEV 1-0/FVC (4.8%). The main advantages of the instrument are: lightness, easy operation, ruggedness and low cost; it seems mainly indicated for use in large scale field surveys.


Recent Advances of 68Ga-Labeled PET Radiotracers with Nitroimidazole in the Diagnosis of Hypoxia Tumors.
Positron emission tomography (PET) is a noninvasive molecular imaging method extensively applied in the detection and treatment of various diseases. Hypoxia is a common phenomenon found in most solid tumors. Nitroimidazole is a group of bioreducible pharmacophores that selectively accumulate in hypoxic regions of the body. Over the past few decades, many scientists have reported the use of radiopharmaceuticals containing nitroimidazole for the detection of hypoxic tumors. Gallium-68, a positron-emitting radioisotope, has a favorable half-life time of 68 min and can be conveniently produced by 68Ge/68Ga generators. Recently, there has been significant progress in the preparation of novel 68Ga-labeled complexes bearing nitroimidazole moieties for the diagnosis of hypoxia. This review provides a comprehensive overview of the current status of developing 68Ga-labeled radiopharmaceuticals with nitroimidazole moieties, their pharmacokinetics, and in vitro and in vivo studies, as well as PET imaging studies for hypoxic tumors.


Polyvalent Proteins, a Pervasive Theme in the Intergenomic Biological Conflicts of Bacteriophages and Conjugative Elements.
Intense biological conflicts between prokaryotic genomes and their genomic parasites have resulted in an arms race in terms of the molecular "weaponry" deployed on both sides. Using a recursive computational approach, we uncovered a remarkable class of multidomain proteins with 2 to 15 domains in the same polypeptide deployed by viruses and plasmids in such conflicts. Domain architectures and genomic contexts indicate that they are part of a widespread conflict strategy involving proteins injected into the host cell along with parasite DNA during the earliest phase of infection. Their unique feature is the combination of domains with highly disparate biochemical activities in the same polypeptide; accordingly, we term them polyvalent proteins. Of the 131 domains in polyvalent proteins, a large fraction are enzymatic domains predicted to modify proteins, target nucleic acids, alter nucleotide signaling/metabolism, and attack peptidoglycan or cytoskeletal components. They further contain nucleic acid-binding domains, virion structural domains, and 40 novel uncharacterized domains. Analysis of their architectural network reveals both pervasive common themes and specialized strategies for conjugative elements and plasmids or (pro)phages. The themes include likely processing of multidomain polypeptides by zincin-like metallopeptidases and mechanisms to counter restriction or CRISPR/Cas systems and jump-start transcription or replication. DNA-binding domains acquired by eukaryotes from such systems have been reused in XPC/RAD4-dependent DNA repair and mitochondrial genome replication in kinetoplastids. Characterization of the novel domains discovered here, such as RNases and peptidases, are likely to aid in the development of new reagents and elucidation of the spread of antibiotic resistance.IMPORTANCE This is the first report of the widespread presence of large proteins, termed polyvalent proteins, predicted to be transmitted by genomic parasites such as conjugative elements, plasmids, and phages during the initial phase of infection along with their DNA. They are typified by the presence of multiple domains with disparate activities combined in the same protein. While some of these domains are predicted to assist the invasive element in replication, transcription, or protection of their DNA, several are likely to target various host defense systems or modify the host to favor the parasite's life cycle. Notably, DNA-binding domains from these systems have been transferred to eukaryotes, where they have been incorporated into DNA repair and mitochondrial genome replication systems.


Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring : A Nationwide Cohort Study.
Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown. To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes. Nationwide prospective registry-based cohort study. Denmark from 1997 to 2016. All liveborn singletons from mothers without histories of diabetes or essential hypertension. Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings. Of 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring (n = 5298) had the reference birth defect frequency (adjusted odds ratio [aOR], 0.98 [95% CI, 0.85 to 1.14]). Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92). Offspring whose fathers filled a metformin prescription in the year before (n = 1751) or after (n = 2484) sperm development had reference birth defect frequencies (aORs, 0.88 [CI, 0.59 to 1.31] and 0.92 [CI, 0.68 to 1.26], respectively), as did unexposed siblings of exposed offspring (3.2%; exposed vs. unexposed OR, 1.54 [CI, 0.94 to 2.53]). Among metformin-exposed offspring, genital birth defects, all in boys, were more common (aOR, 3.39 [CI, 1.82 to 6.30]), while the proportion of male offspring was lower (49.4% vs. 51.4%, P = 0.073). Information on underlying disease status was limited. Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation. National Institutes of Health.


Nursing's contributions to innovative hospital design.
With nearly $200 billion of healthcare construction expected by 2015, nurse leaders must expand their knowledge and capabilities in healthcare design. This bimonthly department, edited by Jaynelle F. Stichler, DNSc, RN, FACHE, prepares nurse leaders to use the evidence-based design process to ensure that new, expanded, and renovated hospitals facilitate optimal patient outcomes, enhance the work environment for healthcare providers, and improve organizational performance. The guest authors of this article feature a new interdisciplinary model of graduate education that is focused on preparing design and healthcare professionals to work collaboratively in creating optimal healthcare designs that foster safety and efficiency.


ROS1-Rearranged Lung Cancer Successfully Resected after Response to Crizotinib: A Case Report.
The usefulness of molecularly targeted therapy as a preoperative therapy for the c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer has not been established. We present the case of ROS1- rearranged lung cancer successfully resected after response to crizotinib. The patient was a 71-year-old woman with prolonged cough. She was diagnosed with ROS1-rearranged lung adenocarcinoma (cT4N2M0, stage IIIB). After eight weeks of crizotinib treatment, right upper lobectomy with chest wall resection, angioplasty, and bronchoplasty were performed. The postoperative course was good, and the patient survived for 41 months after the surgery without recurrence. Surgical resection after molecularly targeted therapy for ROS1-positive lung cancer may lead to good local control.


[The discourse of the criteria for quality in qualitative research].
Despite being a young discipline nursing science in the German-speaking area produces a growing number of research studies; many of them are qualitative in nature. Thus, it seems timely to raise questions about which quality criteria should be used to conduct and evaluate qualitative studies and to discuss how the scientific community in general and nursing science handle these issues. This article includes additional aspects of the recent quality discourse in German social and nursing science literature. For a better appraisal of the German-speaking discourse it will be taken a short comparison with current articles of English-speaking journals. A terminal discussion of the main results follows.


Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions.
On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently serious illness due to invasion by opportunistic bacteria. The health burden due to complicated scabies causing cellulitis, bacteraemia and sepsis, heart and kidney diseases in resource-poor communities is extreme. Co-infections of group A streptococcus (GAS) and scabies mites is a common phenomenon in the tropics. Both pathogens produce multiple complement inhibitors to overcome the host innate defence. We investigated the relative role of classical (CP), lectin (LP) and alternative pathways (AP) towards a pyodermic GAS isolate 88/30 in the presence of a scabies mite complement inhibitor, SMSB4. Opsonophagocytosis assays in fresh blood showed baseline immunity towards GAS. The role of innate immunity was investigated by deposition of the first complement components of each pathway, specifically C1q, FB and MBL from normal human serum on GAS. C1q deposition was the highest followed by FB deposition while MBL deposition was undetectable, suggesting that CP and AP may be mainly activated by GAS. We confirmed this result using sera depleted of either C1q or FB, and serum deficient in MBL. Recombinant SMSB4 was produced and purified from Pichia pastoris. SMSB4 reduced the baseline immunity against GAS by decreasing the formation of CP- and AP-C3 convertases, subsequently affecting opsonisation and the release of anaphylatoxin. Our results indicate that the complement-inhibitory function of SMSB4 promotes the survival of GAS in vitro and inferably in the microenvironment of the mite-infested skin. Understanding the tripartite interactions between host, parasite and microbial pathogens at a molecular level may serve as a basis to develop improved intervention strategies targeting scabies and associated bacterial infections.


Ternary Sn-Ti-O based nanostructures as anodes for lithium ion batteries.
SnO(x) (x = 0, 1, 2) and TiO(2) are widely considered to be potential anode candidates for next generation lithium ion batteries. In terms of the lithium storage mechanisms, TiO(2) anodes operate on the base of the Li ion intercalation-deintercalation, and they typically display long cycling life and high rate capability, arising from the negligible cell volume change during the discharge-charge process, while their performance is limited by low specific capacity and low electronic conductivity. SnO(x) anodes rely on the alloying-dealloying reaction with Li ions, and typically exhibit large specific capacity but poor cycling performance, originating from the extremely large volume change and thus the resultant pulverization problems. Making use of their advantages and minimizing the disadvantages, numerous strategies have been developed in the recent years to design composite nanostructured Sn-Ti-O ternary systems. This Review aims to provide rational understanding on their design and the improvement of electrochemical properties of such systems, including SnO(x) -TiO(2) nanocomposites mixing at nanoscale and nanostructured Sn(x) Ti(1-x) O(2) solid solutions doped at the atomic level, as well as their combinations with carbon-based nanomaterials.


Determination of levels of specific IgA to the HspX recombinant antigen of Mycobacterium tuberculosis for the diagnosis of pleural tuberculosis.
To evaluate the accuracy of determining specific IgA to HspX recombinant antigen in pleural fluid and serum samples for the diagnosis of pleural tuberculosis in patients with pleural effusion. This was a cross-sectional study. Serum and pleural fluid samples of patients with pleural effusion and suspected of having pleural tuberculosis were tested with indirect ELISA in order to determine the optical density of specific IgA to HspX. We evaluated serum and pleural fluid samples from 132 patients: 97 diagnosed with pleural tuberculosis (study group) and 35 diagnosed with pleural effusion due to other causes (control group). The determination of IgA in pleural fluid satisfactorily discriminated between pleural tuberculosis patients and control patients. The sensitivity of the test in pleural fluid and in serum was 69% and 30%, respectively, whereas the specificity was 83% and 84%, respectively. Our data suggest that this test can be used in the diagnosis of pleural tuberculosis. Further studies, involving larger patient samples and different epidemiological scenarios, are warranted.


Factors contributing to the wear of polyethylene in clinical practice.
Wear of polyethylene is a major contributor in the failure of total joint replacement. A number of different factors may predispose to increased wear of polyethylene. These can be broadly categorized as (i) material polymorphism, (ii) poor design features and (iii) three-body wear. Many of these factors contribute to the wear encountered in clinical practice. These mechanisms are reviewed and examples identified in which they have resulted in increased wear.


Cat scratch disease in a child.
We report a case of a 9-year-old girl scratched on the right side of her neck by a kitten about one month prior to admission. She was well until three weeks later when she developed enlarged right neck masses, a pustula on the scratch site, right injected conjunctiva, headache, general malaise and fever, thus fulfilling the clinical criteria for CSD. Initially, she was treated by a practicing physician but the manifestations persisted for one week. After admission, leukocytosis and a mildly elevated erythrocyte sedimentary rate were noted. The serum IgG titer to Bartonella henselae was performed by means of indirect fluorescent antibody (IFA) test at the National Institute of Preventive Medicine. The serum titer of anti-B, henselae Ig G was 1:256 and greater (> or = 1:256). The positive serum titer(negative titer being < 1:64) to B, henselae, the organism thought to be responsible for CSD, also supports this diagnosis. She was treated with a 7-day course of intravenous gentamicin and the fever subsided within 24 hours. Following this, she improved clinically and was discharged one week later. One month after discharge, she remained well with no palpable neck masses.


The risk factors of early implant failure: A retrospective study of 6113 implants.
The risk factors of early implant failure were controversial among previous studies, especially for implants in different sites. To analyze the rate and risk factors of early implant failure occurring before the placement of final prosthesis. A retrospective study was conducted based on electrical medical records of patients who received dental implant placement from 2015 to 2019. Generalized estimation equation analyses were used to explore potential risk factors influencing early implant failure. Overall, 6113 implants in 3785 patients were included. The rate of early implant failure was 1.6% at patient level and 1.2% at implant level. The early implant failure was significantly associated with implants in the posterior maxilla, with specific surface modifications and in previously augmented sites (p < 0.05). Risk factors for maxillary implants included surface modification and bone augmentation procedures (p < 0.01), whereas risk factors for mandibular implants included gender and bone augmentation procedures (p < 0.05). For implants placed in previously augmented sites, implants placed in the anterior mandible had a higher risk of early failure (p < 0.05). The risk factors for early implant failures varied among different sites; hence, they should be comprehensively considered in presurgical treatment plan.


Clinical services in community pharmacies: a scoping review of policy and social implications.
Clinical services have allowed pharmacists to shift from product-oriented to patient-oriented services. However, the policy and social implications of clinical services in community pharmacies are not well described. The purpose of this scoping review was to identify these implications. We searched Pubmed and Embase, from inception to March 2019, as well as grey literature for publications that discussed policy (e.g. pharmacy model and pharmacist status) or social (e.g. role of pharmacists and interprofessional collaboration) implications of clinical services. Publications had to address clinical services provided by pharmacists in community settings that target the global long-term care of patients. We extracted data related to the implications and classified them into themes thereafter. The search process identified 73 relevant publications, of which 13 were included in regard to policy implications and 60 relative to social implications. Two themes emerged from policy implications: implementation and characteristics of policies, and professional status. Pharmacists' independence from distribution, financial coverage of clinical services and innovative models of practice were addressed. Social implications involved three themes: roles and interprofessional collaboration, changes in practice and barriers and model of practices and services. Perceptions of pharmacists' skills, organisational barriers, time constraints, lack of self-confidence and cultural shifts required to implement clinical services were included in these themes. Our review demonstrates the changing role of community pharmacists in provision of clinical services within the healthcare system. The range of clinical services varies widely from one setting to another. The context of community pharmacy is not well suited to these changes in practice.


High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?
Standard treatments for neoplastic meningitis are only modestly effective and are associated with significant morbidity. Isolated reports suggest that concurrent systemic and intrathecal (i.t.) therapy may be more effective than i.t. therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high-dose (HD) intravenous (i.v.) methotrexate (MTX) as the sole treatment for neoplastic meningitis. Sixteen patients with solid-tumor neoplastic meningitis received one to four courses (mean, 2.3 courses) of HD (8 g/m2 over 4 hours) i.v. MTX and leucovorin rescue. Serum and CSF MTX concentrations were measured daily. Toxicity, response, and survival were retrospectively compared with a reference group of 15 patients treated with standard i.t. MTX during the same time interval. Peak methotrexate concentrations ranged from 3.7 to 55 micromol/L (mean, 17.1 micromol/L) in CSF and 178 to 1,700 micromol/L (mean, 779 micromol/L) in serum. Cytotoxic CSF and serum MTX concentrations were maintained much longer than with i.t. dosing. Toxicity was minimal. Cytologic clearing was seen in 81% of patients compared with 60% of patients treated intrathecally (P = .3). Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months in the i.t. MTX group (P = .003). HD i.v. MTX is easily administered and well tolerated. This regimen achieves prolonged cytotoxic serum MTX concentrations and CSF concentrations at least comparable to those achieved with standard i.t. therapy. Cytologic clearing and survival may be superior in patients treated with HD i.v. MTX. Prospective studies and a reconsideration of the use of i.t. chemotherapy for patients with neoplastic meningitis are warranted.


Primary malignant melanoma of the vagina.
Malignant melanoma originating in the vagina is considered extremely rare and has a very poor prognosis. We report a case of a 70-year-old woman with primary malignant melanoma of the vagina, and discuss the importance of prognostic factors and the efficacy of adjuvant chemotherapy.


The effects of prior exposure to prism lenses on de novo motor skill learning.
Motor learning involves plasticity in a network of brain areas across the cortex and cerebellum. Such traces of learning have the potential to affect subsequent learning of other tasks. In some cases, prior learning can interfere with subsequent learning, but it may be possible to potentiate learning of one task with a prior task if they are sufficiently different. Because prism adaptation involves extensive neuroplasticity, we reasoned that the elevated excitability of neurons could increase their readiness to undergo structural changes, and in turn, create an optimal state for learning a subsequent task. We tested this idea, selecting two different forms of learning tasks, asking whether exposure to a sensorimotor adaptation task can improve subsequent de novo motor skill learning. Participants first learned a new visuomotor mapping induced by prism glasses in which prism strength varied trial-to-trial. Immediately after and the next day, we tested participants on a mirror tracing task, a form of de novo skill learning. Prism-trained and control participants both learned the mirror tracing task, with similar reductions in error and increases in distance traced. Both groups also showed evidence of offline performance gains between the end of day 1 and the start of day 2. However, we did not detect differences between groups. Overall, our results do not support the idea that prism adaptation learning can potentiate subsequent de novo learning. We discuss factors that may have contributed to this result.