Targeted Delivery of Sucrose-Coated Nanocarriers with Chemical Cargoes to the Plant Vasculature Enhances Long-Distance Translocation.
Current practices for delivering agrochemicals are inefficient, with only a fraction reaching the intended targets in plants. The surfaces of nanocarriers are functionalized with sucrose, enabling rapid and efficient foliar delivery into the plant phloem, a vascular tissue that transports sugars, signaling molecules, and agrochemicals through the whole plant. The chemical affinity of sucrose molecules to sugar membrane transporters on the phloem cells enhances the uptake of sucrose-coated quantum dots (sucQD) and biocompatible carbon dots with β-cyclodextrin molecular baskets (suc-β-CD) that can carry a wide range of agrochemicals. The QD and CD fluorescence emission properties allowed detection and monitoring of rapid translocation (<40 min) in the vasculature of wheat leaves by confocal and epifluorescence microscopy. The suc-β-CDs more than doubled the delivery of chemical cargoes into the leaf vascular tissue. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that the fraction of sucQDs loaded into the phloem and transported to roots is over 6.8 times higher than unmodified QDs. The sucrose coating of nanoparticles approach enables unprecedented targeted delivery to roots with ≈70% of phloem-loaded nanoparticles delivered to roots. The use of plant biorecognition molecules mediated delivery provides an efficient approach for guiding nanocarriers containing agrochemicals to the plant vasculature and whole plants.


A rare case of giant cutaneous horn.
Cutaneous horn, a clinical manifestation of hyper-proliferation of compact keratin, can represent a wide array of underlying benign and malignant pathologies. Here we report a unique case of a giant cutaneous horn (7x4x3 cm) that developed on a chronic ulcer in a non sun-exposed area. This case presented challenges in terms of diagnosis and treatment. We also review the literature about this rare condition.


Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial.
Sub-Saharan Africa and southern Asia account for almost 85% of global maternal deaths from post-partum haemorrhage. Early administration of tranexamic acid, within 3 h of giving birth, was shown to reduce the risk of death due to bleeding in women with post-partum haemorrhage in the World Maternal Antifibrinolytic (WOMAN) trial. We aimed to assess the cost-effectiveness of early administration of tranexamic acid for treatment of post-partum haemorrhage. For this economic evaluation we developed a decision model to assess the cost-effectiveness of the addition of tranexamic acid to usual care for treatment of women with post-partum haemorrhage in Nigeria and Pakistan. We used data from the WOMAN trial to inform model parameters, supplemented by estimates from the literature. We estimated costs (calculated in 2016 US$), life-years, and quality-adjusted life-years (QALYs) with and without tranexamic acid, calculated incremental cost-effectiveness ratios (ICERs), and compared these to threshold values in each country. Costs were assessed from the health-care provider perspective and discounted at 3% per year in the base case analysis. We did a series of one-way sensitivity analyses and probabilistic sensitivity analysis to assess the robustness of the results to parameter uncertainty. Early treatment of post-partum haemorrhage with tranexamic acid generated an average gain of 0·18 QALYs at an additional cost of $37·12 per patient in Nigeria and an average gain of 0·08 QALYs at an additional cost of $6·55 per patient in Pakistan. The base case ICER results were $208 per QALY in Nigeria and $83 per QALY in Pakistan. These ICERs were below the lower bound of the cost-effectiveness threshold range in both countries. The ICERs were most sensitive to uncertainty in parameter inputs for the relative risk of death due to bleeding with tranexamic acid, the discount rate, the cost of the drug, and the baseline probability of death due to bleeding. Early treatment of post-partum haemorrhage with tranexamic acid is highly cost-effective in Nigeria and Pakistan, and is likely to be cost-effective in countries in sub-Saharan Africa and southern Asia with a similar baseline risk of death due to bleeding. London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.


Maternal measles antibody decay in rural Bangladeshi infants--implications for vaccination schedules.
Considerable numbers of measles cases occur below the target age for vaccination in the Indian sub-continent. The immunogenicity of measles vaccine in infancy is dependent on the rate of decay in maternal antibody since this antibody interferes with vaccine induced seroconversion. This study investigated maternal antibody decay in a rural population in Bangladesh and evaluated possible risk factors for early decay. Measles antibodies were assessed using both ELISA and Plaque Reduction Neutralization (PRN) test in 330 infant-mother pairs in a cross-sectional survey. PRN was more sensitive method than ELISA for determining antibody levels. Antibody levels decreased rapidly in infants with increasing age. By the age of 5 months, 67% (28/42) infants had practically no protective antibody left (30 mIU ml-1 or below). Only 12% infants at 5 months of age, and 5% at 8 months, had levels greater than 120 mIU ml-1--stated to 'protect' children. Multiple regression showed that maternal age was the only variable associated with the level of antibody (maternal weight, height and MUAC were not associated), decreasing by 1.06 mIU ml-1 for each year of age (P = 0.002). Infant's antibody concentration decreased with age by an average 2 mIU mL-1 for every month of life (P < 0.0001), and was determined by the maternal antibody concentration (P < 0.0001) (child's length, weight, MUAC, mother's gestational age and parity were not associated). The relatively rapid antibody decay suggests that the target age for measles vaccination might be reduced. Further, as the cohort of vaccinated mothers enters reproductive age in Bangladesh, a more rapid decay of antibody may be expected in future generations of Bangladeshi children. The information presented here suggests that a formal trial of standard measles vaccine at younger ages is justified in this population as it could confer considerable benefit in reducing infant measles.


Scapular kinematics during manual wheelchair propulsion in able-bodied participants.
Altered scapular kinematics have been associated with shoulder pain and functional limitations. To understand kinematics in persons with spinal cord injury during manual handrim wheelchair propulsion, a description of normal scapular behaviour in able-bodied persons during this specific task is a prerequisite for accurate interpretation. The primary aim of this study is to describe scapular kinematics in able-bodied persons during manual wheelchair propulsion. Sixteen able-bodied, novice wheelchair users without shoulder complaints participated in the study. Kinematic and kinetic data were collected during a standardized pose in the anatomic posture, frontal-plane arm elevation and low-intensity steady-state handrim wheelchair propulsion and upper-body Euler angles were calculated. Scapulothoracic joint orientations in a static position were 36.7° (SD 5.4°), 6.4° (SD 9.1°) and 9.1° (SD 5.7°) for respectively protraction, lateral rotation and anterior tilt. At 80° of arm elevation in the frontal plane, the respective values of 33.4° (SD 8.0°), 23.9° (SD 5.4°) and 4.1° (SD 11.3°) were found. During the push phase of manual wheelchair propulsion, the mean scapular rotations were respectively 32.7° (SD 7.1°), 7.1° (SD 9.2°) and 9.8° (SD 8.3°). The orientation of the scapula in a static pose, during arm elevation and in manual wheelchair propulsion in able-bodied participants showed similar patterns to a previous study in persons with para- and tetraplegia. These values provide a reference for the investigation of the scapular movement pattern in wheelchair-dependent persons and its relation to shoulder complex abnormalities.


Influence of tyrosine-derived moieties and drying conditions on the formation of helices in gelatin.
The single and triple helical organization of protein chains strongly influences the mechanical properties of gelatin-based materials. A chemical method for obtaining different degrees of helical organization in gelatin is covalent functionalization, while a physical method for achieving the same goal is the variation of the drying conditions of gelatin solutions. Here we explored how the introduction of desaminotyrosine (DAT) and desaminotyrosyl tyrosine (DATT) linked to lysine residues of gelatin influenced the kinetics and thermodynamic equilibrium of the helicalization process of single and triple helices following different drying conditions. Drying at a temperature above the helix-to-coil transition temperature of gelatin (T > T(c), called v(short)) generally resulted in gelatins with relatively lower triple helical content (X(c,t) = 1-2%) than lower temperature drying (T < T(c), called v(long)) (X(c,t) = 8-10%), where the DAT(T) functional groups generally disrupted helix formation. While different helical contents affected the thermal transition temperatures only slightly, the mechanical properties were strongly affected for swollen hydrogels (E = 4-13 kPa for samples treated by v(long) and E = 120-700 kPa for samples treated by v(short)). This study shows that side group functionalization and different drying conditions are viable options to control the helicalization and macroscopic properties of gelatin-based materials.


Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.
The outcome of systemic chemotherapy in metastatic hepatocellular carcinoma (HCC) patients had been disappointing. Based on the demonstrated antitumor activities and different mechanisms of action and toxicity profiles, we designed a phase II trial of combination therapy with doxorubicin and cisplatin in metastatic HCC patients anticipating a synergistic interaction of the combination. From January 1998 to January 2003, 42 consecutive patients with metastatic HCC were accrued. The regimen consisted of doxorubicin 60 mg/m2 delivered as an intravenous infusion over 30 min on day 1, followed by cisplatin 60 mg/m2 infused over 1 h on day 1. The cycle was repeated every 28 days. The objective tumor response was evaluated after two or three courses of chemotherapy. The serum alpha-fetoprotein level was measured at the start of every cycle. In total, 122 cycles of the regimen were administered, with a median of three cycles per patient (range one to eight cycles). The median age of the patients was 45 years (range 19-61 years), and 37 were evaluable for treatment response. The objective response rate was 18.9% (95% CI 8.0-35%) with one complete response and six partial responses. Six patients (16.2%) had stable disease and 24 patients (64.9%) had progression. Median overall survival of 37 patients was 7.3 months (95% CI 5.9-8.6 months). The median time to progression of all evaluable patients was 6.6 months (95% CI 5.4-7.8 months). Of 37 evaluable patients, 12 32.4%, 95% CI 18.0-49.8%) showed more than 50% decrease in AFP level from their baseline AFP and the median time to decrease in AFP by more than 50% was 1.8 months with a range of 0.7-4.7 months. The chemotherapy was well tolerated and the most common grade 3/4 side effects were neutropenia (14.3%), thrombocytopenia (11.9%), and diarrhea (9.5%). Combination chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed modest antitumor activity with relatively tolerable adverse effects. The objective response rate of the regimen was comparable to those found in other phase II trials, but the search for the optimal chemotherapy should be continued.


Low EGF in myeloablative allotransplantation: association with severe acute GvHD in BMT CTN 0402.
Epidermal growth factor (EGF) is a recently described biomarker of acute GvHD (aGvHD). Whether low plasma EGF prior to hematopoietic cell transplantation (HCT) predisposes to the development of aGvHD, or whether EGF levels fall because of severe aGvHD, is unknown. To evaluate this, we tested plasma samples collected at pre-HCT baseline, day +28 and day +100 during the course of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. We found that baseline EGF plasma concentrations were three-fold lower in HCT recipients compared to donors (24.3 vs 76.0 pg/mL, P<0.01). Ninety-one patients (43%) had a markedly low plasma EGF at pre-HCT baseline, defined as <2.7 pg/mL-an optimal cutpoint associated with development of grade III-IV aGvHD. Patients with these low EGF levels at pre-HCT baseline had a 2.9-fold increased risk of grade III-IV aGvHD by day +100. Patients with low EGF at day +28 after HCT had an increased risk of death (relative risk 2.3, P=0.02) by 1 year due to transplant-related toxicities, especially aGvHD. Our results suggest that very low plasma EGF early in the HCT process may predispose patients to an increased risk of death, potentially due to epithelial damage and limited repair capacity.


ABO/Rh Blood Groups and Risk of HIV Infection and Hepatitis B Among Blood Donors of Abidjan, Côte D'ivoire.
Hepatitis B and HIV infection are two viral infections that represent real global public health problems. In order to improve their management, some hypotheses suggest that genetic predispositions like ABO and Rh blood groups would influence the occurrence of these diseases. The aim of the present study was to examine the association between ABO and Rhesus blood groups and the susceptibility to HIV infection and hepatitis B. We conducted a cross-sectional and analytical study in a population of voluntary blood donors in the Blood Transfusion Center of Abidjan. All blood donors who donated blood between January and June 2014 were tested for HBs antigen and anti-HIV antibodies (ELISA tests) and were ABO typed. The total number of examined blood donors during this period was 45,538, of which 0.32% and 8.07% were respectively infected with HIV and hepatitis B virus. O-group donors were more infected than non-O donors. Our study is an outline concerning the search for a link between ABO and Rh blood groups and hepatitis B and HIV infection. Further studies should be conducted to confirm the interaction between these two infections and contribute to the search for new therapeutic approaches.


The ethylene response factor Pti5 contributes to potato aphid resistance in tomato independent of ethylene signalling.
Ethylene response factors (ERFs) comprise a large family of transcription factors that regulate numerous biological processes including growth, development, and response to environmental stresses. Here, we report that Pti5, an ERF in tomato [Solanum lycopersicum (Linnaeus)] was transcriptionally upregulated in response to the potato aphid Macrosiphum euphorbiae (Thomas), and contributed to plant defences that limited the population growth of this phloem-feeding insect. Virus-induced gene silencing of Pti5 enhanced aphid population growth on tomato, both on an aphid-susceptible cultivar and on a near-isogenic genotype that carried the Mi-1.2 resistance (R) gene. These results indicate that Pti5 contributes to basal resistance in susceptible plants and also can synergize with other R gene-mediated defences to limit aphid survival and reproduction. Although Pti5 contains the ERF motif, induction of this gene by aphids was independent of ethylene, since the ACC deaminase (ACD) transgene, which inhibits ethylene synthesis, did not diminish the responsiveness of Pti5 to aphid infestation. Furthermore, experiments with inhibitors of ethylene synthesis revealed that Pti5 and ethylene have distinctly different roles in plant responses to aphids. Whereas Pti5 contributed to antibiotic plant defences that limited aphid survival and reproduction on both resistant (Mi-1.2+) and susceptible (Mi-1.2-) genotypes, ethylene signalling promoted aphid infestation on susceptible plants but contributed to antixenotic defences that deterred the early stages of aphid host selection on resistant plants. These findings suggest that the antixenotic defences that inhibit aphid settling and the antibiotic defences that depress fecundity and promote mortality are regulated through different signalling pathways.


Contact Allergy Cross-reactions: Retrospective Clinical Data and Review of the Literature.
We discuss cross-reactions that can occur when a patient allergic to a specific allergen also reacts to a similar allergen. Currently, The American Contact Dermatitis Society Contact Allergy Management Program, which allows physicians to identify safe products for their patients, uses a 10% threshold to distinguish significant cross-reactors. New clinical data from a patch testing center along with previous data in the literature are analyzed to help determine whether current cross-reactor definitions are reasonable or should be altered.


The Cdc2/Cdk1 inhibitor, purvalanol A, enhances the cytotoxic effects of taxol through Op18/stathmin in non-small cell lung cancer cells in vitro.
Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation. In combination, purvalanol A and taxol mainly decreased the expression of oncoprotein 18 (Op18)/stathmin and phosphorylation at Ser16 and Ser38, while purvalanol A alone inhibited the phosphorylation of Op18/stathmin at all 4 serine sites. Co-treatment with purvalanol A and taxol weakened the expression of Bcl-2 and activated the extrinsic cell death pathway through the activation of caspase-3 and caspase-8. Further experiments indicated that Cdc2 kinase activities, including the expression of Cdc2 and the level of phospho-Cdc2 (Thr161) were significantly higher in taxol-resistant NCI-H1299 cells compared with the relatively sensitive CNE1 cells before and following treatment with taxol. These findings suggest that Cdc2 is positively associatd with the development of taxol resistance. The Cdc2 inhibitor, purvalanol A, enhanced the cytotoxic effects of taxol through Op18/stathmin. Our findings may prove to be useful in clinical practice, as they may provide a treatment strategy with which to to reduce the doses of taxol applied clinically, thus alleviating the side-effects.


[The role of nephrologist in treatment of multiple myeloma].
Multiple myeloma (MM) is malignant disease caused by proliferation of malignant clone of terminally differentiated plasma-cells. Clinical features may include symptoms of bone disease, unexplained back-pain, fractures, anaemia, kidney failure, oedema, hypercalcaemia, bacterial infections, impaired hemostasis, peripheral neuropathy and hyperviscosity. Impairment of renal function occurs in 50% of patients with different forms of kidney disease. Majority of patients have precipitation of monoclonal immunoglobulins or their fragments in kidney. Hypercalcemia, dehydration, infections and nephrotoxic drugs contribute to development of kidney injury. Treatment consists of chemotherapy for primary disease, with plasma exchange in cases of hyperviscosity. Supportive treatment should include rehydration, treatment of hyperuricemia and hypercalcaemia. Patients with end-stage renal disease could be treated with peritoneal dialysis or haemodialysis. Renal transplantation is rarely offered to this group of patients.


Childhood blindness: dateline Africa.
Prevalence rates of childhood blindness and infant and childhood mortality in Africa are the highest in the world. Major factors contributing to these high rates are similar for both blindness and mortality: malnutrition, measles and other acute febrile infections, malnutrition with xerophthalmia, and limited or poor access to preventive and curative health services. Because of high national growth rates, stagnant economies, and the failure of national health care systems to expand with rapidly growing populations, childhood blindness in Africa likely will remain a significant international public health problem for the foreseeable future.


Synthesis and nematocidal activity of aralkyl- and aralkenylamides related to piperamide on second-stage larvae of Toxocara canis.
Seventy-nine aralkyl- and aralkenylamides related to piperamides were synthesized and their nematocidal activity against second-stage larvae of dog roundworm, Toxocara canis, was examined. The activity was greatly dependent on the alkyl chain length and the nature of the amine moiety, but was scarcely affected by the presence or absence of double bond(s) in the chain. The alkyl chain lengths which showed the strongest activity in a series of homologues were m = 11 for the pyrrolidine amides and m = 13 for the N-methylpiperazine amides. Although piperamides (3,4-methylenedioxyphenyl homologues) showed the strongest activity among the homologues tested, methoxy substituent(s) on the aromatic ring did not have much effect on the activity. However, conversion of the methoxy group to a hydroxy group greatly decreased the activity and shortened the chain length giving the strongest activity. Calculated log P values of non-phenolic aryl-piperamides fell in the range from 3.5 to 4.5, whereas those of hydroxyphenyl-piperamides were smaller, suggesting that different mechanisms are involved in the nematocidal activity of phenolic and non-phenolic compounds.


Pandemic Seasonal H1N1 Reassortants Recovered from Patient Material Display a Phenotype Similar to That of the Seasonal Parent.
We have previously shown that 11 patients became naturally coinfected with seasonal H1N1 (A/H1N1) and pandemic H1N1 (pdm/H1N1) during the Southern hemisphere winter of 2009 in New Zealand. Reassortment of influenza A viruses is readily observed during coinfection of host animals and in vitro; however, reports of reassortment occurring naturally in humans are rare. Using clinical specimen material, we show reassortment between the two coinfecting viruses occurred with high likelihood directly in one of the previously identified patients. Despite the lack of spread of these reassortants in the community, we did not find them to be attenuated in several model systems for viral replication and virus transmission: multistep growth curves in differentiated human bronchial epithelial cells revealed no growth deficiency in six recovered reassortants compared to A/H1N1 and pdm/H1N1 isolates. Two reassortant viruses were assessed in ferrets and showed transmission to aerosol contacts. This study demonstrates that influenza virus reassortants can arise in naturally coinfected patients. Reassortment of influenza A viruses is an important driver of virus evolution, but little has been done to address humans as hosts for the generation of novel influenza viruses. We show here that multiple reassortant viruses were generated during natural coinfection of a patient with pandemic H1N1 (2009) and seasonal H1N1 influenza A viruses. Though apparently fit in model systems, these reassortants did not become established in the wider population, presumably due to herd immunity against their seasonal H1 antigen.


Anti-ribosomal antibodies bind the Sm proteins D and B/B'.
In order to analyse the specificity of human anti-ribosomal P protein antibodies, anti-ribosomal P protein antibodies were affinity-purified from the sera of lupus patients. Their binding capacity towards recombinant SmD protein and recombinant SmB/B' protein was evaluated by immunoblot and ELISA. Epitope mapping of SmD was performed by means of synthetic peptides. Anti-ribosomal P protein antibodies bound recombinant SmD (5/10) and SmB/B' (4/10) on immunoblot; 6/10 showed binding capacity to SmD on ELISA. Inhibition experiments using ELISA confirmed the specificity of this binding. Our data indicate the cross-reactivity of spontaneously developed anti-ribosomal P protein antibodies with the B/B' and D constituents of the Sm complex. The coexistence of anti-Sm and anti-ribosomal antibodies in lupus sera may therefore be due, at least in part, to the reactivity of a single autoantibody population.


Cure in a case of primary hepatic lymphoma.
Primary hepatic lymphoma is rare malignancy. Cures in this disease are uncommon. We report a young male who was diagnosed as a case of primary lymphoma of the liver in 1992. He was treated with chemotherapy only, which included CHOP (Cyclophosphamide, Adriamycin, Vincristine and Prednisolone) - six cycles; and IMVP-16 (Ifosfamide, Methotrexate and Etoposide) -four cycles. The patient is now disease free and alive for more than five years.


ap-9-(meta-tert-butylphenyl)fluorene.
The title compound, C(23)H(22), (I), crystallizes in an ap conformationThe designations sp (synperiplanar) and ap (antiperiplanar) for these fluorene rotamers are in accordance with Rule E-6.6, IUPAC Tentative Rules, Section E, Fundamental Stereochemistry [J. Org. Chem. (1970), 35, 2861]. and its melt readily recrystallizes on cooling, in contrast to the corresponding 9-fluorenol compound, (II), which is sp and which melts without decomposition and fails to recrystallize over a long period. Both of these differences are ascribed to the intermolecular hydrogen bonding in (II), which is absent in (I) and which leads to distinctly different molecular packing in the two compounds.


In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway.
Estrone and estradiol concentrations in breast tumor tissue are an order of magnitude higher than circulating plasma levels in postmenopausal women with breast cancer. Local production of estrogen in the neoplastic tissue is one of several possible explanations for this plasma/tissue gradient. This study evaluated breast tumor estrogen production via the estrone sulfate to estrone (sulfatase) pathway and compared this with the androstenedione to estrone (aromatase) system in human and rodent mammary tumors. Estrogen production from estrone sulfate was related linearly with time and tissue concentrations, exhibited an apparent Km of 20 microM, and produced a linear Eadie-Hofstee kinetic plot consistent with a single class of enzymatic sites. Measurement of sulfatase in 35 human breast tumors using enzyme saturating conditions revealed estrone production ranging from 0.8-125 mumol/g protein . h. The corresponding range in host mammary tumors was 3.5-7.1 mumol/g protein . h. In human breast tumors, sulfatase activity did not correlate with the levels of estrogen receptor or progesterone receptor. Comparison of sulfatase with aromatase activity in human tumors at physiological levels of substrate revealed estrone formation via sulfatase of 2.8 pmol estrone produced/g protein . h, while aromatase produced only 0.27 pmol/g protein . h. In rat mammary tumors, sulfatase activity was similar to that in human tumors, whereas aromatase activity could not be detected, even with a highly sensitive assay. Thus, estrone sulfatase appears to be the enzyme primarily responsible for intratissue estrone production in hormone-dependent breast carcinomas.


Mycobacterium xenopi infection and aspergilloma.
In 11 patients with pulmonary disease due to Mycobacterium xenopi, definite aspergilloma subsequently developed in five and probable aspergilloma in a further three. Those patients with evidence of Aspergillus infection formed a much higher proportion (73%) than in previous reports of patients with mycobacterial disease. Patients with both Mycobacterium xenopi infection and aspergilloma appear to have a poor prognosis.


[Effect of baicalin on HSP70 expression of hippocampal neurons in focal brain ischemia-reperfusion injury rats].
To investigate the effect of baicalin on the hippocampal neuronal apoptosis and the expression of HSP70 in rats with focal brain ischemia-reperfusion injury. One hundred and twenty male Wistar rats were randomly divided into six groups:sham operated group, ischemia-reperfusion group, nimodipine group and three baicalin groups,to which baicalin was administered at doses of 50, 100 and 200 mg x kg(-1), separately. The models of focal brain ischemia-reperfusion injury induced by middle cerebral artery occlusion (MCAO) were used in this study. HE stain was used to observe the pathological changes. Flow cytometry (FCM) was used for determination of neuronal apoptosis. HSP70 protein expression of the neurons was detected with immunohistochemistry. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of the mRNA level of HSP70. Baicalin can significantly relieve the pathological changes and inhibit apoptosis in hippocampus CA1 area, and at the same time increase the expression of HSP70 and HSP70 mRNA. Baicalin can relieve brain damage induced by focal brain ischemia-reperfusion in rats, which may be related to inhibiting the process of the neuronal apoptosis. The mechanism of antiapoptosis effect of baicalin may be related to the promotion of transcription of HSP70 mRNA and increasing the expression of the protein.


In silico drug discovery: solving the "target-rich and lead-poor" imbalance using the genome-to-drug-lead paradigm.
Advances in genomics, proteomics, and structural genomics have identified a large number of protein targets. Virtual screening has gained popularity in identifying drug leads by computationally screening large numbers of chemicals against experimentally determined protein targets. In that context, there continues to be a "target-rich and lead-poor" imbalance, reflecting an insufficiency of chemists pursuing drug discovery in academia, the challenge of engaging more chemists in this area of research, and a paucity of available protein target structures. This imbalance in manpower and structural information can be ameliorated, in part, by adapting a "genome-to-drug-lead" approach, in which chemicals can be virtually screened against computer-predicted protein targets, within the context of the US National Science Foundation's petascale computing initiative. This approach offers a solution to reduce manpower requirements for more chemists to experimentally search for drug leads, which represent one of the greatest limitations to drug discovery and better exploits the extensive availability of drug targets at the gene level, ultimately improving the success of moving discoveries from the laboratory to the patient.


The Effects of Hormone Contraceptives and Menstruation on Object Memory and Spatial Ability in Young Women.
The aim of this study is to examine the relationship between hormone contraceptive use and menstruation on cognitive performance in young women. The object array task assessed object memory and a mental rotations test assessed spatial ability in women taking hormone contraceptives and naturally cycling women. Women taking hormone contraceptives were significantly better than naturally cycling women at identifying novel objects on an object array, but not on performance of a mental rotations task. There were also no significant differences in either task between naturally cycling women who were menstruating and those who were not menstruating during testing. The results of this study suggest that women taking hormone contraceptives outperformed naturally cycling women in recalling the identities of objects. The findings from this study help to further demonstrate the relationship between ovarian hormones and cognitive performance and add to the understanding of how hormone contraceptives affect cognition.


Specificities and clinical significance of anti-cytoskeleton antibodies in anti-smooth muscle antibody-positive patients with chronic liver disease C.
We investigated the specificities and characteristics of anti-cytoskeleton antibodies in 13 anti-smooth muscle antibody (ASMA)-positive patients with chronic liver disease C (CLD-C), and compared them with those in 7 ASMA-positive patients with autoimmune hepatitis (AIH), and 6 ASMA-positive patients with chronic liver disease B (CLD-B). Anti-microfilaments (anti-MF) were found not only in 6/7 AIH patients (85.7%), but also in 8/13 CLD-C patients (61.5%) with a relatively high incidence, when compared with 1/6 CLD-B patients (16.7%), while, there was no significant difference in the incidence of anti-intermediate filaments (anti-IMF), especially anti-IMF IgM, among these patient groups. Among the patients with CLD-C, the mean levels of serum gammaglobulin and IgG in the anti-MF-positive patients were 2.46 +/- 1.03 g/dl and 3277 +/- 1089 mg/dl, respectively, which were higher than those in the anti-MF-negative patients (1.60 +/- 0.53 g/dl, 2245 +/- 610 mg/dl) and those in the patients with CLD-B (1.60 +/- 0.57 g/dl, 2192 +/- 339 mg/dl). Furthermore, 4 of the 8 anti-MF-positive patients with CLD-C satisfied the serological criteria for the diagnosis of AIH. These findings suggest that autoimmune mechanisms might be involved in the pathogenesis of anti-MF-positive CLD-C, and that anti-MF might be used as a marker.


IFN beta accelerates autoimmune type 1 diabetes in nonobese diabetic mice and breaks the tolerance to beta cells in nondiabetes-prone mice.
Genetic and environmental factors are decisive in the etiology of type 1 diabetes. Viruses have been proposed as a triggering environmental event and some evidences have been reported: type I IFNs exist in the pancreata of diabetic patients and transgenic mice expressing these cytokines in beta cells develop diabetes. To determine the role of IFNbeta in diabetes, we studied transgenic mice expressing human IFNbeta in the beta cells. Autoimmune features were found: MHC class I islet hyperexpression, T and B cells infiltrating the islets and transfer of the disease by lymphocytes. Moreover, the expression of beta(2)-microglobulin, preproinsulin, and glucagon in the thymus was not altered by IFNbeta, thus suggesting that the disease is caused by a local effect of IFNbeta, strong enough to break the peripheral tolerance to beta cells. This is the first report of the generation of NOD (a model of spontaneous autoimmune diabetes) and nonobese-resistant (its homologous resistant) transgenic mice expressing a type I IFN in the islets: transgenic NOD and nonobese-resistant mice developed accelerated autoimmune diabetes with a high incidence of the disease. These results indicate that the antiviral cytokine IFNbeta breaks peripheral tolerance to beta cells, influences the insulitis progression and contributes to autoimmunity in diabetes and nondiabetes- prone mice.


Plutonium content of human placental tissues after occupational exposure.
The placenta and umbilical cord were obtained following a normal live delivery from a volunteer donor who had received an accidental inhalation intake of plutonium 12 years prior to her pregnancy (Case 0777). Her employer estimated the intake to be about 73 Bq Class W plutonium. Based on bioassay results and clearance models in use at that time, they calculated her body content at the beginning of pregnancy to be about 5.6 Bq with an average concentration of approximately 60 mBq kg(-1). The placenta and cord from this pregnancy, along with the placenta and cord from a donor with no known exposure to plutonium (Case 0835), were divided and assayed for plutonium by ultrasensitive fission track analysis at two collaborating laboratories. Placental 239Pu concentration values obtained by the two laboratories for Case 0777 agreed within a factor of 2 and were several-fold greater than for the control, Case 0835, as well as values that had been reported by others for unexposed populations. There was no elevated concentration of plutonium in the umbilical cord from the exposed person. The data yielded values of 0.16 and 0.27 for placental to maternal concentrations (CPl: CM) that were of the same order of magnitude as the value of 0.1 the ICRP calculated for intakes before pregnancy.


Sunscreen-Based Photocages for Topical Drugs: A Photophysical and Photochemical Study of A Diclofenac-Avobenzone Dyad.
Photosensitization by drugs is a problem of increasing importance in modern life. This phenomenon occurs when a chemical substance in the skin is exposed to sunlight. Photosensitizing drugs are reported to cause severe skin dermatitis, and indeed, it is generally advised to avoid sunbathing and to apply sunscreen. In this context, the nonsteroidal anti-inflammatory drug (NSAID) diclofenac is a photosensitive drug, especially when administered in topical form. In this work, efforts have been made to design and study an innovative pro-drug/pro-filter system containing diclofenac and the UVA filter avobenzone in order to develop a safer use of this topical drug. The design is based on the presence of a well-established photoremovable phenacyl group in the avobenzone structure. Steady-state photolysis of the dyad in hydrogen-donor solvents, monitored by UV-Vis spectrophotometry and HPLC, confirms the simultaneous photorelease of diclofenac and avobenzone. Laser flash photolysis and phosphorescence emission experiments allow us to gain insight into the photoactive triplet excited-state properties of the dyad. Finally, it is shown that avobenzone provides partial photoprotection to diclofenac from photocyclization to carbazole derivatives.


Experimental inoculation of North American opossums (Didelphis virginiana) with Mycobacterium bovis.
Eight North American opossums (Didelphis virginiana) were inoculated with 1 x 10(5) colony forming units of Mycobacterium bovis to investigate their potential as reservoir hosts for bovine tuberculosis in Michigan. Four animals received this dose orally and four were inoculated intramuscularly (i.m.). In each group, two animals were euthanized 1 mo postinoculation (PI) and two at 2 mo PI. Four control animals were housed separately and sacrificed in the same manner as those inoculated. One of four orally inoculated opossums and three of four i.m.-inoculated opossums were positive for M. bovis by culture of tissues obtained at necropsy. The oral recipient had positive cultures from intestine and pooled lymphoid samples. Pooled lymphoid samples were positive in three i.m.-inoculated animals and two of these also had positive liver and lung cultures. One animal with gross and histologic lesions compatible with tuberculosis had negative tissue cultures. The findings suggest that opossums are susceptible to M. bovis infection by multiple routes, although their relative susceptibility compared to true reservoir hosts appears to be low.


Survival prognosis model for elderly women with epithelial ovarian cancer based on the SEER database.
We aimed to analyze the risk factors of elderly women with epithelial ovarian cancer (EOC) using data on the SEER database, and to generate a nomogram model their 1-, 3-, and 5-year prognoses. The resulting nomogram model should be useful for clinical diagnoses and treatment. We collected clinical data of women older than 70 years with epithelial ovarian cancer (diagnosed on the basis of surgical pathology) from the SEER database including datasets between 2010 and 2019. We randomly grouped the data into two groups (7:3 ratio) using the R language software. We divided the independent prognostic factors obtained by univariate and multi-factor Cox regression analyses into training and validation sets, and we plotted the same independent prognostic factors in a nomogram model of overall survival (OS) at 1, 3, and 5 years. We used the C-index, calibration curve, and area under the curve to validate the nomograms. We further evaluated the model and its clinical applicability using decision curve analyses. We identified age, race, marital status, histological type, AJCC staging, differentiation degree, unilateral and bilateral tumor involvement, number of positive lymph nodes, chemotherapy, surgery, sequence of systemic treatment versus surgery, and time from diagnosis to treatment as independent prognostic factors for elderly women with EOC (P < 0.5). The C-indexes were 0.749 and 0.735 in the training and validation sets, respectively; the ROC curves showed that the AUC of each prognostic factor was greater than 0.7; and, the AUC values predicted by the line plot were similar in the training and validation sets. The decision curves suggest that this line plot model has a high clinical value for predicting overall survivals at 1, 3, and 5 years in elderly women with EOC. The nomogram model in this study can provide an accurate assessment of the overall survival of women older than 70 years with EOC at the time of the first treatment, and it provides a basis for individualized clinical treatment.


Disposition of 1,2-[14C]Dibromoethane in male Wistar rats.
In this study the disposition of 1,2-[14C]dibromoethane (1, 2-[14C]DBE) was investigated in male Wistar rats. 1,2-DBE is a cytotoxic and carcinogenic compound that has been used as an additive in leaded gasoline and as a fumigant. 1,2-[14C]DBE was administered orally or iv. Radioactivity was recovered (mostly within 48 hr after administration) in urine (75-82% of the dose), feces (3.2-4% of the dose), and expired air (0.53-7.2% of the dose). One hundred-sixty-eight hours after administration of 1,2-[14C]DBE, most of the radioactivity in tissues was found in the liver, lungs, and kidneys (<1% of the dose) and the red blood cells (0.3% of the dose). Identified urinary metabolites were S-(2-hydroxyethyl)mercapturic acid, thiodiacetic acid, and thiodiacetic acid sulfoxide, together accounting for, on average, 78% of the total amount of radioactivity in urine. In addition to S-(2-hydroxyethyl)mercapturic acid, thiodiacetic acid, and thiodiacetic acid sulfoxide, several compounds were anticipated as potential urinary metabolites of 1,2-DBE, i.e. S-(carboxymethyl)mercapturic acid, S-(2-hydroxyethyl)thioacetic acid, S-(2-hydroxyethyl)thiopyruvic acid, S-(carboxymethyl)thiopyruvic acid, S-(2-hydroxyethyl)thiolactic acid, and S-(carboxymethyl)thiolactic acid. All of the postulated urinary metabolites were synthesized and searched for in urine samples. None of these metabolites could be detected in urine, however. The data obtained in the present study might be useful for risk assessment and biomonitoring studies of 1,2-DBE and will also be used to further validate a physiologically based pharmacokinetic model for 1, 2-DBE in rats and humans that was recently developed.


Toward a framework for patient education. An analysis of enablement.
Patient education is an activity that nurses engage in on a regular basis, yet in the literature it is seldom examined as a patient-centered process. The desire to describe the process of patient education in terms that were not content-driven was the guiding force for an examination of the concept of enablement. The purpose of this article is to describe an analysis that resulted in a definition of enablement and the identification of three components: means, abilities, and opportunities. Model, related, and contrary cases are provided. The findings of this examination are used to propose a potential framework for designing, implementing, and evaluating patient education across content areas.


Investigation of Demodex folliculorum frequency in patients with polycystic ovary syndrome.
Background: Demodex mites are acari that reside in the pilosebaceous unit of the skin and have been associated with skin disorders. The objective of this study was to investigate the prevalence of Demodex folliculorum (D. folliculorum) mites in polycystic ovary syndrome patients as well as to examine the relationship between Demodex infestation and the presence of acne and oily or dry skin types in polycystic ovary syndrome patients. 41 polycystic ovary syndrome patients and 47 non-polycystic ovary syndrome control subjects were enrolled in the study. polycystic ovary syndrome was diagnosed according to the revised 2003 ESHRE/ASRM polycystic ovary syndrome Consensus Workshop Group diagnostic criteria. Microscopic examination of D. folliculorum mites was carried out by standardized skin surface biopsy. The result was considered positive when there were more than 5 mites per cm2. D. folliculorum was positive in 53.7% of the polycystic ovary syndrome patients and 31.9% of the non-polycystic ovary syndrome group (p=0.052). Demodex positivity was significantly associated with acne (p=0.003) and oily skin (p=0.005) in the polycystic ovary syndrome patients but not in the controls. Our study is limited by the relatively small number of subjects and the observational nature of the study design. Demodex mites might have a role in acne pathogenesis in patients with polycystic ovary syndrome. Anti-Demodex treatment may increase the response to treatment of acne. Further studies are indicated.


[Identification of an old frozen alcohol blood sample using a genetic probe technique].
Determination of ethanol concentration in a blood sample drawn from a person who caused a serious car crash showed a level which was markedly above the upper limit tolerated legally i.e. 0.08%. At the court hearing the accused car driver challenged the drunken driving charge and claimed that there might have been a mix up of the blood samples, whereby his was replaced by another blood sample, since the tube containing his blood was not marked with his name. The blood sample had been stored without anticoagulants for about 6 months at -20 degrees C. Due to haemolysis it was impossible to determine conventional haemogenetic marker systems. We therefore tried to extract DNA from the blood sample and to determine the restriction fragment length polymorphism (RFLP) by means of five DNA probes recognizing highly polymorphic single-locus systems as described by Jeffreys et al. We analyzed the RFLP's of both the old blood sample and of fresh blood drawn from the accused car driver and we were able to identify the blood sample as certainly having been taken from the accused.


Development of an Off-the-Shelf Tissue-Engineered Sinus Valve for Transcatheter Pulmonary Valve Replacement: a Proof-of-Concept Study.
Tissue-engineered heart valves with self-repair and regeneration properties may overcome the problem of long-term degeneration of currently used artificial prostheses. The aim of this study was the development and in vivo proof-of-concept of next-generation off-the-shelf tissue-engineered sinus valve (TESV) for transcatheter pulmonary valve replacement (TPVR). Transcatheter implantation of off-the-shelf TESVs was performed in a translational sheep model for up to 16 weeks. Transapical delivery of TESVs was successful and showed good acute and short-term performance (up to 8 weeks), which then worsened over time most likely due to a non-optimized in vitro valve design. Post-mortem analyses confirmed the remodelling potential of the TESVs, with host cell infiltration, polymer degradation, and collagen and elastin deposition. TESVs proved to be suitable as TPVR in a preclinical model, with encouraging short-term performance and remodelling potential. Future studies will enhance the clinical translation of such approach by improving the valve design to ensure long-term functionality.


MiRSEA: Discovering the pathways regulated by dysfunctional MicroRNAs.
Recent studies have shown that dysfunctional microRNAs (miRNAs) are involved in the progression of various cancers. Dysfunctional miRNAs may jointly regulate their target genes and further alter the activities of canonical biological pathways. Identification of the pathways regulated by a group of dysfunctional miRNAs could help uncover the pathogenic mechanisms of cancer and facilitate development of new drug targets. Current miRNA-pathway analyses mainly use differentially-expressed miRNAs to predict the shared pathways on which they act. However, these methods fail to consider the level of differential expression level, which could improve our understanding of miRNA function. We propose a novel computational method, MicroRNA Set Enrichment Analysis (MiRSEA), to identify the pathways regulated by dysfunctional miRNAs. MiRSEA integrates the differential expression levels of miRNAs with the strength of miRNA pathway associations to perform direct enrichment analysis using miRNA expression data. We describe the MiRSEA methodology and illustrate its effectiveness through analysis of data from hepatocellular cancer, gastric cancer and lung cancer. With these analyses, we show that MiRSEA can successfully detect latent biological pathways regulated by dysfunctional miRNAs. We have implemented MiRSEA as a freely available R-based package on CRAN (https://cran.r-project.org/web/packages/MiRSEA/).


Amoebae, Giant Viruses, and Virophages Make Up a Complex, Multilayered Threesome.
Viral infection had not been observed for amoebae, until the Acanthamoeba polyphaga mimivirus (APMV) was discovered in 2003. APMV belongs to the nucleocytoplasmatic large DNA virus (NCLDV) family and infects not only A. polyphaga, but also other professional phagocytes. Here, we review the Megavirales to give an overview of the current members of the Mimi- and Marseilleviridae families and their structural features during amoebal infection. We summarize the different steps of their infection cycle in A. polyphaga and Acanthamoeba castellani. Furthermore, we dive into the emerging field of virophages, which parasitize upon viral factories of the Megavirales family. The discovery of virophages in 2008 and research in recent years revealed an increasingly complex network of interactions between cell, giant virus, and virophage. Virophages seem to be highly abundant in the environment and occupy the same niches as the Mimiviridae and their hosts. Establishment of metagenomic and co-culture approaches rapidly increased the number of detected virophages over the recent years. Genetic interaction of cell and virophage might constitute a potent defense machinery against giant viruses and seems to be important for survival of the infected cell during mimivirus infections. Nonetheless, the molecular events during co-infection and the interactions of cell, giant virus, and virophage have not been elucidated, yet. However, the genetic interactions of these three, suggest an intricate, multilayered network during amoebal (co-)infections. Understanding these interactions could elucidate molecular events essential for proper viral factory activity and could implicate new ways of treating viruses that form viral factories.


Structure elucidation and antioxidant activity of (-)-isosilandrin isolated from Silybum marianum L.
A regioisomer of the known flavanolignan (-)-silandrin (3a), named (-)-isosilandrin (8a), was isolated from the fruits of a white-flowered variant of Silybum marianum L. populated in Hungary. Its structure was established both by spectroscopic methods and total synthesis, and its absolute configuration was determined by means of circular dichroism. This compound showed stronger inhibitory activity on the superoxide anion (O2*-) release by human polymorphonuclear leukocytes (PMNL) than (+)-silybin (1a,b).


Psoriasis and Psoriatic Arthritis.
Psoriasis is a dynamic systemic disease that can have a profound affect on a patient's self-esteem. Fortunately, numerous therapeutic advances have been made over the last 10 years. In order to help patients manage their disease, healthcare providers should be aware of the modifiable risk factors that may exacerbate psoriasis. Additionally, exploring the impact the disease has on a patient and how it may change over their lifespan will help ensure appropriate therapies are used. Patients are unique so one medication will not fit all of our patients' needs. In this paper, the authors look at available treatment options for psoriasis and psoriatic arthritis. Educating psoriasis patients, in addition to collaborating with patients and other healthcare providers, may help initiate therapies that will result in patients living their lives to the fullest.


Cartilaginous Choristoma of Tonsil: A hidden clinical entity.
Choristoma is a tumor like mass which is an ectopic rest of normal tissue due to embryological developmental defect. The presence of choristoma in tonsil is extremely rare. On histopathological examination, mature hyaline cartilage were found surrounded by lymphoid follicles. We present a case of cartilaginous choristoma with the complaint of recurrent tonsillitis.


Intravenous Lidocaine for Acute Pain: A Systematic Review.
This systematic review evaluates the safety and efficacy of intravenous (IV) lidocaine for the treatment of acute pain in adult patients. The PubMed database was searched for randomized controlled trials, retrospective cohort studies, case series, and case reports evaluating the use of IV lidocaine for the treatment of acute pain in adult patients, published between January 1970 and January 2018. The primary outcome was pain reduction via the Visual Analog Scale, Verbal Rating Scale, or Numeric Rating Scale among patients treated with IV lidocaine and placebo or active controls. Safety outcomes included both nonserious and serious adverse events. A total of 347 titles and abstracts were screened, and after full-text review, 13 studies met the inclusion criteria involving 512 patients. The four active controls studied were IV morphine, IV ketorolac, IV dihydroergotamine (DHE), and IV chlorpromazine (CPZ). The dosing of IV lidocaine varied among studies between a weight-based dose of a 1- to 2-mg/kg bolus, a fixed-bolus dose of 50-100 mg, and a 1-mg/kg/hour continuous infusion. Monitoring of serum lidocaine concentrations was not done routinely. Intravenous lidocaine had superior efficacy to morphine for renal colic and critical limb ischemia, superior efficacy to DHE for acute migraine, and equivalent efficacy to ketorolac for acute radicular lower back pain. However, lidocaine was less effective than CPZ for the treatment of acute migraine. The most common adverse event reported among all studies were neurologic effects such as altered mental status and slurred speech. Due to the inconsistency in dosing, length of administration, and lack of serum monitoring, the absolute safety of IV lidocaine for acute pain is unknown. Larger, prospective studies are needed before the routine use of IV lidocaine can be recommended for all types of acute pain.


Self-consistent molecular field theory for packing in classical liquids.
Building on a quasichemical formulation of solution theory, this paper proposes a self-consistent molecular field theory for packing problems in classical liquids, and tests the theoretical predictions for the excess chemical potential of the hard sphere fluid. Results are given for the self-consistent molecular fields obtained, and for the probabilities of occupancy of a molecular observation volume. For this system, the excess chemical potential predicted is nearly as accurate as the most accurate prior theories, specifically the scaled particle (Percus-Yevick compressibility) theory. A compact formula is obtained to throw light on the variation of the chemical potential with the radius of a distinguished hard sphere solute in general solvents. It is argued that the present approach is particularly simple, permits a natural description of possibilities for multiphasic behavior of the solution, and should provide a basis for a molecular-scale description of more complex solutions.


Myasthenia gravis in otolaryngological practice.
A retrospective study of 48 unselected patients with myasthenia gravis was undertaken to evaluate the head and neck manifestations of this disease and to examine the role of the otolaryngologist in diagnosis and management. Oropharyngeal features were found in 56% of patients at presentation. In 20 the initial complaint was of one or more symptoms referable to the upper aerodigestive tract, whilst in 9 (18.8%) these were the only symptoms. The importance of maintaining a high index of clinical suspicion is emphasized, as the early muscle weakness is invariably mild and fluctuant. Contemporary aspects of the aetiology, diagnosis and management are considered. Particular attention is focused on the characteristics of the stapedius reflex in this disorder, as this is probably the most sensitive objective test for assessing defective neuromuscular transmission.


Comparison of the immune response to vaccination with pigeon circovirus recombinant capsid protein (PiCV rCP) in pigeons uninfected and subclinically infected with PiCV.
Infections with immunosuppressive pigeon circovirus (PiCV) pose the most severe health problem to the global pigeon breeding. The vaccination with immunogenic PiCV recombinant capsid protein (PiCV rCP) is a potential tool for disease control. Because of the high prevalence of PiCV asymptomatic infections, the subclinically infected pigeons will be vaccinated in practice. The aim of this study was to answer a question if vaccination of asymptomatic, infected with PiCV pigeons induces a similar immune response to PiCV rCP as in uninfected birds. One hundred and twenty 6-week-old carrier pigeons were divided into 4 groups (2 groups of naturally infected and uninfected with PiCV individuals). Birds from groups V and V1 were vaccinated twice with PiCV rCP mixed with an adjuvant, whereas pigeons from groups C and C1 were immunized with an adjuvant only. The expression of genes encoding IFN-γ, CD4, and CD8 T lymphocyte receptors; the number of anti-PiCV rCP IgY-secreting B cells (SBC) and anti-PiCV rCP IgY were evaluated 2, 21, 39 and 46 days post vaccination (dpv). Study results showed that the expression of CD8 and IFN-γ genes was higher in both groups of infected pigeons than in the uninfected birds, irrespective of vaccination. In the uninfected birds, the expression of these genes was insignificantly higher in the vaccinated pigeons. The anti-PiCV rCP IgY-SBC were detected on 2 and 23 dpv and seroconversion was noted on 23 and 39 dpv in V and V1 groups, respectively. In the light of the results obtained, it could be concluded that pigeon circovirus recombinant capsid protein elicits the immune response in both naturally infected and uninfected pigeons, but its rate varies depending on PiCV infectious status. The infection with PiCV masks the potential cellular immune response to the vaccination with PiCV rCP and leads to the suppression of humoral immunity.


Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice.
Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviours and their effects on homeostatic functions in a live mammal remains unclear. Here we capture the spatiotemporal dynamics of individual epithelial behaviours by imaging wound re-epithelialization in live mice. Differentiated cells migrate while the rate of differentiation changes depending on local rate of migration and tissue architecture. Cells depart from a highly proliferative zone by directionally dividing towards the wound while collectively migrating. This regional coexistence of proliferation and migration leads to local expansion and elongation of the repairing epithelium. Finally, proliferation functions to pattern and restrict the recruitment of undamaged cells. This study elucidates the interplay of cellular repair behaviours and consequent changes in homeostatic behaviours that support tissue-scale organization of wound re-epithelialization.


Comparing surgically induced astigmatism calculated by means of simulated keratometry versus total corneal refractive power.
To evaluate surgically induced astigmatism as computed by means of either simulated keratometry (KSIM) or total corneal refractive power (TCRP) after temporal incisions. Prospective observational study including 36 right eyes undergoing cataract surgery. Astigmatism was measured preoperatively during the 3-month follow-up period using Pentacam. Surgically induced astigmatism was computed considering anterior corneal surface astigmatism at 3 mm with KSIM and considering both corneal surfaces with TCRP from 1 to 8 mm (TCRP3 for 3 mm). The eyes under study were divided into two balanced groups: LOW with KSIM astigmatism <0.90 D and HIGH with KSIM astigmatism ≥0.90 D. Resulting surgically induced astigmatism values were compared across groups and measuring techniques by means of flattening, steepening, and torque analysis. Mean surgically induced astigmatism was higher in the HIGH group (0.31 D @ 102°) than in the LOW group (0.04 D @ 16°). The temporal incision resulted in a steepening in the HIGH group of 0.15 D @ 90°, as estimated with KSIM, versus 0.28 D @ 90° with TCRP3, but no significant differences were found for the steepening in the LOW group or for the torque in either group. Differences between KSIM- and TCRP3-based surgically induced astigmatism values were negligible in LOW group. Surgically induced astigmatism was considerably higher in the high-astigmatism group and its value was underestimated with the KSIM approach. Eyes having low astigmatism should not be included for computing the surgically induced astigmatism because steepening would be underestimated.


A systematic review and meta-analysis of outcomes in hybrid constructs for multi-level lumbar degenerative disc disease.
A systematic review and meta-analysis was performed to assess the effect of hybrid constructs which involve a total disc arthroplasty (TDA) with stand-alone anterior lumbar interbody fusion (ALIF) versus non-hybrid constructs including multi-level TDA, multi-level transforaminal lumbar interbody fusion (TLIF) with posterior transpedicular fixation or multi-level stand-alone ALIF as a surgical intervention for degenerative disc disease (DDD) in the lumbar spine. Primary outcomes analysed included the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for back pain. A systematic search of Medline, Embase, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Google Scholar was undertaken by two separate reviewers and a meta-analysis of the outcomes was performed. Three studies met our search criteria. When comparing hybrid constructs to multi-level TDA or lumbar fusion (LF) improvements in back pain were found with a VAS back pain score reduction of 1.38 (P<0.00001) postoperatively and a VAS back pain score reduction of 0.99 points (P=0.0006) at 2-years follow-up. Results so far slightly favour clinically significant improved VAS back pain score outcomes postoperatively and at 2-years follow-up for hybrid constructs in multi-level lumbar DDD of the spine when compared with non-hybrid multi-level LF or TDA. It cannot however be concluded that a hybrid construct is superior to multi-level LF or TDA based on this meta-analysis. The results highlight the need for further prospective studies to delineate best practice in the management of degenerative disc disease of the lumbar spine.


Measuring the internalized stigma of parents of persons with a serious mental illness: the factor structure of the parents' internalized stigma of mental illness scale.
Research has revealed that approximately one third of persons with a serious mental illness (SMI) experience elevated internalized stigma, which is associated with a large number of negative outcomes. Family members of persons with SMI are also often subject to stigma, but the degree to which these experiences are internalized and lead to self-stigma has rarely been studied. The present study investigated the factor structure of a modification of the Internalized Stigma of Mental Illness (ISMI) scale by Ritsher, Otilingam, and Grajales (Psychiatry Res 121:31-49, 2003). A central assumption of this investigation was that the factor structure of the Parents' Internalized Stigma of Mental Illness (PISMI) scale would be similar to the factor structure of the ISMI scale. A total of 194 parents of persons with SMI completed the PISMI scale. The results revealed that the PISMI scale has high internal consistency and that it is made up of three distinctive factors: discrimination experience, social withdrawal and alienation, and stereotype endorsement. These factors are similar, but not identical, to the factors that underlie the ISMI scale. This study's findings also indicate that parents' prominent reaction to self-stigma is stereotype endorsement.


Drug misuse/abuse intervention: a schematic tool for decision making and planning.
A catalytic conceptual tool is presented to facilitate the concerned reader's decision making with regard to personally developing and/or participating in more effective drug misuse/abuse intervention efforts. The reader is asked to consider and select the interface between 16 areas of potential intervention, 4 sources of drug abuse typologies, and 6 foci for intervention which is most suitable to his/her roles, skills, interests, and concerns.


Sleep regulation of the distribution of cortical firing rates.
Sleep is thought to mediate both mnemonic and homeostatic functions. However, the mechanism by which this brain state can simultaneously implement the 'selective' plasticity needed to consolidate novel memory traces and the 'general' plasticity necessary to maintain a well-functioning neuronal system is unclear. Recent findings show that both of these functions differentially affect neurons based on their intrinsic firing rate, a ubiquitous neuronal heterogeneity. Furthermore, they are both implemented by the NREM slow oscillation, which also distinguishes neurons based on firing rate during sequential activity at the DOWN→UP transition. These findings suggest a mechanism by which spiking activity during the slow oscillation acts to maintain network statistics that promote a skewed distribution of neuronal firing rates, and perturbation of that activity by hippocampal replay acts to integrate new memory traces into the existing cortical network.


Controlling light by light in a one-dimensional resonant photonic crystal.
We consider the interaction and stability of gap solitons in a one-dimensional, resonant, photonic crystal with a defect state produced by a linear localized mode, or by an incoherent pump. Soliton propagation is investigated using both an analytical treatment and the direct numerical integration of the two-wave Maxwell-Bloch equations. Our results demonstrate that the soliton can be trapped, reflected from, or tunnel through the defect state.


Determinants of genetic diversity.
Genetic polymorphism varies among species and within genomes, and has important implications for the evolution and conservation of species. The determinants of this variation have been poorly understood, but population genomic data from a wide range of organisms now make it possible to delineate the underlying evolutionary processes, notably how variation in the effective population size (Ne) governs genetic diversity. Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' - the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels. It seems that linked selection plays an important part both in the overall genetic diversity of a species and in the variation in diversity within the genome. Genetic diversity also seems to be predictable from the life history of a species.


Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance.
The lymphocyte-specific Cas family protein Cas-L (Crk-associated substrate lymphocyte type) has been implicated to function in lymphocyte movement, mediated mainly by integrin signaling. However, its physiological role is poorly understood. In this study we analyzed the function of Cas-L in lymphocytes using gene-targeted mice. The mutant mice showed a deficit of marginal zone B (MZB) cells and a decrease of cell number in secondary lymphoid organs. An insufficient chemotactic response and perturbed cell adhesion were observed in Cas-L-deficient lymphocytes, suggesting that the aberrant localization was responsible for the deficit of MZB cells. Moreover, we found that lymphocyte trafficking was altered in Cas-L-deficient mice, which gave a potential reason for contraction of secondary lymphoid tissues. Thus, Cas-L affects homeostasis of MZB cells and peripheral lymphoid organs, which is considered to be relevant to impaired lymphocyte migration and adhesion.


The influence of interface roughness on Mössbauer filtration of synchrotron radiation at an isotope interface.
The influence of interface irregularities on synchrotron radiation Mössbauer filtration at an isotope interface is examined theoretically. Calculations are performed for a random-roughness interface model for a (56)Fe/(57)Fe isotope interface. The analysis shows that, despite a drop in the efficiency in the real structures compared with the idealized structures, the efficiency of Mössbauer filtration of synchrotron radiation remains high enough to ensure a successful experiment. In particular it was found that, as well as a regular saw-like profile of the external interface, a randomly rough profile of the external interface may also be used in the Mössbauer filtration experiment if the roughness parameters satisfy certain demands.


Linear dielectric response of clustered living cells.
The dielectric behavior of a linear cluster of two or more living cells connected by tight junctions is analyzed using a spectral method. The polarizability of this system is obtained as an expansion over the eigenmodes of the linear response operator, showing a clear separation of geometry from electric parameters. The eigenmode with the second largest eigenvalue dominates the expansion as the junction between particles tightens, but only when the applied field is aligned with the cluster axis. This effect explains a distinct low-frequency relaxation observed in the impedance spectrum of a suspension of linear clusters.


Synthesis of single-walled carbon nanotubes through micropores of surface-treated zeolites by catalyst-supported chemical vapor deposition.
Cobalt nanoparticle-loaded Y-type zeolite (HSZ390HUA) without outer-surface Co aggregates is successfully prepared by Co impregnation reaction followed by surface treatment using tetraethylammoniumbromide having larger molecule size than the orifice size of the Y-type zeolite. Single-wall carbon nanotubes (SWCNTs) have been synthesized by ethanol catalyst-supported chemical vapor deposition at 973 K for 10 min using as-produced and surface-treated Co-loaded zeolites. The SWCNTs synthesized are characterized by transmission electron microscopy, Raman spectroscopy and photoluminescence spectroscopy. The products synthesized by using the as-produced Co-loaded zeolites are mostly multi-wall carbon nanotubes (MWCNTs) with larger diameter than the orifice of zeolite and carbon nanocapsules (CNCs). In contrast, SWCNTs with diameters of 0.66-0.85 nm, which are approximately the same as that of the orifice size, are selectively synthesized by using the surface-treated Co-loaded zeolites.


A case of secondary erythromelalgia with unusual histological findings.
Erythromelalgia clinically presents with episodic burning, erythema, and warmth of acral sites. It can be divided into primary and secondary associated with myeloproliferative and autoimmune conditions. Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular edema, and chronic inflammation with sparse lymphocytic infiltrate. We report a case of a 55-year-old man with classical secondary erythromelalgia clinically; however, he had unusual histological findings on biopsy comprising of acute perivascular infiltrate and perivascular mucin. This is the first report of such findings in the context of secondary erythromelalgia.


Non-selective signal loss in the 13C CPMAS NMR spectra of soil organic matter. Investigations of particle size fractions.
In 13C cross-polarisation magic angle spinning (CPMAS) spectra of soil samples, the paramagnetic soil constituents partially discriminate against the signal intensity of the 13C atoms. The aim of the present study was to check to what extent this signal depression depends on the paramagnetic ion content and if it is selective for a certain kind of carbon species. The spectra of a variety of particle size fractions of five quite different soils were recorded. A procedure was developed to compare quantitatively the relative carbon content of the different spectra. It was found that iron ions differ in their efficiency to discriminate against the carbon signals. Nevertheless a strong linear correlation between the detectability of carbon and cube root(wt.%Fe) was observed for both the total signal and the signal of the different carbon species as well. This underlines that iron ions mainly influence the depression of the 13C signal in soil spectra. Furthermore we found, that for C: Fe ratios of 1.5 to 20 non-selective signal losses dominate. Despite a high percentage of non-detectable carbon (up to 90%), the 13C CPMAS spectra of our soil samples correctly reflect the relative composition of soil organic matter.


Size-resolved infrared spectroscopic study of structural transitions in sodium-doped (H₂O)n clusters containing 10-100 water molecules.
In water clusters containing 10-100 water molecules the structural transition takes place between "all surface" structures without internally solvated water molecules to amorphous water clusters with a three dimensionally structured interior. This structural evolution is explored with rigorous size selection by IR excitation modulated photoionization spectroscopy of sodium-doped (H2O)n clusters. The emergence of fully coordinated interior water molecules is observed by an increased relative absorption from 3200 to 3400 cm(-1) in agreement with theoretical predictions and earlier experimental studies. The analysis has also shown that the intermediate-sized water clusters (n = 40-65) do not smoothly link the structures in the largest and smallest analyzed size regions (n = 15-35 and n = 100-150) in line with previous reports suggesting the appearance of exceptionally stable water cluster isomers at n = 51, 53, 55, and 57. In the size range from n = 49 to n = 55 a reduced ion yield, a plateau in the total IR signal gain and signatures in the distribution of free OH stretch oscillator absorption have been observed. Recently reported putative global minima structures for n = 51 and n = 54 point to the presence of periplanar interior rings in odd-numbered clusters in this size range, which may affect cluster (surface) stability and the shape of the free OH stretch absorption peak. Potential links between pure and sodium-doped water cluster structures and the signatures of solvated electrons in photoelectron spectra of anionic water clusters are discussed.


Use of the Medicare database in epidemiologic and health services research: a valuable source of real-world evidence on the older and disabled populations in the US.
Medicare is the federal health insurance program for individuals in the US who are aged ≥65 years, select individuals with disabilities aged <65 years, and individuals with end-stage renal disease. The Centers for Medicare and Medicaid Services grants researchers access to Medicare administrative claims databases for epidemiologic and health outcomes research. The data cover beneficiaries' encounters with the health care system and receipt of therapeutic interventions, including medications, procedures, and services. Medicare data have been used to describe patterns of morbidity and mortality, describe burden of disease, compare effectiveness of pharmacologic therapies, examine cost of care, evaluate the effects of provider practices on the delivery of care and patient outcomes, and explore the health impacts of important Medicare policy changes. Considering that the vast majority of US citizens ≥65 years of age have Medicare insurance, analyses of Medicare data are now essential for understanding the provision of health care among older individuals in the US and are critical for providing real-world evidence to guide decision makers. This review is designed to provide researchers with a summary of Medicare data, including the types of data that are captured, and how they may be used in epidemiologic and health outcomes research. We highlight strengths, limitations, and key considerations when designing a study using Medicare data. Additionally, we illustrate the potential impact that Centers for Medicare and Medicaid Services policy changes may have on data collection, coding, and ultimately on findings derived from the data.


Characterization Study of Patients Presenting to an Acute Care Pediatric Hospital Identified With Avoidant/Restrictive Food Intake Disorder.
Nearly one-quarter of individuals diagnosed with avoidant/restrictive food intake disorder (ARFID) require medical admission. There have been efforts to characterize ARFID in outpatient and intensive day treatment settings; however, authors of few studies have examined this presentation in the inpatient pediatric hospital setting. In this study, we aim to further characterize patients presenting to the hospital with concerns for ARFID. This study involved a retrospective chart review of medically admitted patients with ARFID seen by the psychiatry consultation service at a tertiary care New England pediatric hospital from 2015 to 2016. The typical hospitalized patient with ARFID was a 12.9-year-old, white girl with previous history of outpatient mental health treatment, anxiety disorder, and gastrointestinal-related diagnoses admitted to adolescent medicine or pediatric hospitalist services with >1 year of feeding difficulties often triggered by a precipitating event. Despite >80% of subjects receiving evaluations as outpatients for feeding-related concerns, including 60.5% seeing their primary care provider, <20% were diagnosed with ARFID before hospitalization. The average length of admission was 8 days. All imaging, scopes, and swallow studies conducted during the admission were nonrevealing. Almost half of patients required enteral tube feeds, and 63.2% required psychiatric medications during the admission. Only 31.6% of patients had the ARFID diagnosis documented in their discharge notes. Consistent identification of ARFID remains variable, underrecognized by community providers, and underdocumented by hospital providers. Accurate recognition of ARFID and additional study into contributory factors and treatment approaches may help improve effective health care use and treatment outcomes.


Tetra-Sensitive Graft Copolymer Gels as Active Material of Chemomechanical Valves.
Stimuli-responsive hydrogels combine sensor and actuator properties by converting an environmental stimulus into mechanical work. Those materials are highly interesting for applications as a chemomechanical valve in microsystem technologies. However, studies about key characteristics of hydrogels for this application are comparatively rare, and further research is needed to emphasize their real potential. The first part of this study depicts the synthesis of grafted hydrogels based on a poly(N-isopropylacrylamide) backbone and pH-sensitive poly(acrylic acid) graft chains. The chosen approach of grafted hydrogels provides the preparation of multiresponsive hydrogels, which retain temperature sensitivity besides being pH-responsive. A pronounced salt and solvent response is additionally achieved. Key characteristics for an application as a chemomechanical valve of the graft hydrogels are revealed: (1) independently addressable response to all stimuli, (2) significant volume change, (3) sharp transition, (4) reversible swelling-shrinking behavior, and (5) accelerated response time. To prove the concept of multiresponsive hydrogels for flow control, a net-poly(N-acrylamide)-g-poly(acrylic acid) hydrogel containing 0.6 mol % poly(acrylic acid)-vinyl is employed as active material for chemomechanical valves. Remarkably, the chemomechanical valve can be opened and closed in a fluidic platform with four different stimuli.


Pick-and-Place Assembly of Single Microtubules.
Intracellular transport is affected by the filament network in the densely packed cytoplasm. Biophysical studies focusing on intracellular transport based on microtubule-kinesin system frequently use in vitro motility assays, which are performed either on individual microtubules or on random (or simple) microtubule networks. Assembling intricate networks with high flexibility requires the manipulation of 25 nm diameter microtubules individually, which can be achieved through the use of pick-and-place assembly. Although widely used to assemble tiny objects, pick-and-place is not a common practice for the manipulation of biological materials. Using the high-level handling capabilities of microelectromechanical systems (MEMS) technology, tweezers are designed and fabricated to pick and place single microtubule filaments. Repeated picking and placing cycles provide a multilayered and multidirectional microtubule network even for different surface topographies. On-demand assembly of microtubules forms crossings at desired angles for biophysical studies as well as complex networks that can be used as nanotransport systems.


Differential diagnosis of back pain.
Back pain (BP) is among the most common reasons for seeking medical attention worldwide. The nature of BP depends on the causative stimulus and its anatomical location. Clinically, BP is manifested by pain, muscle tension, and stiffness. The development of BP is a very complex, multifactorial process in which not only somatic stimuli (anatomical structures), but also psychosocial effects are involved. Using a variety of criteria, BP can be divided into specific where the cause of pain is known, nonspecific wherein the cause remains unclear, or according to its duration (i.e., acute, subacute, and chronic back pain). Simple low back pain must be distinguished from inflammatory BP. Inflammatory BP is one of the symptoms of spondyloarthritides. It is typically a resting pain of insidious onset, peaking at night or in the morning associated with morning stiffness, improved with exercise, and responding to non-steroidal antirheumatic drugs. A red-flag system was developed for the early identification of at-risk patients with a potentially severe disease presenting with BP. Early diagnosis and identification of the cause of complaints often requires multidisciplinary cooperation. The treatment involves pharmacological agents (analgesic and muscle relaxation therapies) and nonpharmacological approaches (rehabilitation, surgical intervention, etc.).


Measles among healthcare workers in a teaching hospital in central Italy.
The aim of this report is to describe a measles cluster involving health-care workers (HWCs) that occurred in a teaching hospital in central Italy during winter 2011 and the efforts made to promptly identify all the susceptible contacts in order to stop, as soon as possible, transmission of the infection within the hospital. An epidemiological investigation took place. The immunization status of all the exposed individuals was assessed by personal interviews (history of measles or measles vaccine). Serologie screening for personnel not immune to measles was performed. Four cases of measles infection in HCWs were identified; of the 72 HCWs tested for measles immunity, 50 reported a past history of measles, while 22 underwent serological screening, which showed that all were IgG positive except for one case, which was excluded from duty as recommended. Strict adherence to use of alcohol-based hand rub and rapid implementation of appropriate isolation precautions are essential but insufficient to prevent measles outbreaks in hospital settings. Vaccination is the only reliable protection against nosocomial spread of measles. Therefore, assessing the immunization status of HCW and implementing vaccination strategies are needed in order to virtually set to zero the risk of acquiring and spreading measles in healthcare settings.


A new naphthaquinone antibiotic from a new species of yeast.
A fusiform yeast producing limited pseudomycelium and limited true mycelium on malt extract agar has been isolated. This non-fermentative yeast has hyaline cell walls but produces a thick, black oily exudate which is water insoluble and gives the colony a smooth black lacquered appearance. On the basis of morphology and physiology, this organism is distinctive enough to warrant the designation of a new genus. During stationary phase of cultures on chemically defined medium, a deep red substance is produced which has strong antibiotic activity against Staphylococcus aureus in vitro. The substance has been identified as a new natural naphthaquinone of the empirical formula C16H16O7 .


Physical modelling of a harp from Central Africa.
Central Africa harps are string instruments, often anthropomorphic, serving an essential cultural role. Compared to pedal harps, their body is small in size with a soundboard mainly made of animal skin and a neck made of a wood beam. In this paper, a physical model is developed as a tool for assessing the specificities of these musical instruments, from a vibro-acoustic perspective. The modeling strategy is based on the modal Udwadia-Kalaba formalism which is a multibody substructuring technique. Input modal parameters of the body and the strings are experimentally identified and the main steps of the estimation procedures are detailed. The reliability of the physical model is investigated via the comparison between simulated and experimental data for several plucking configurations. Different hypotheses are assessed such as the string/neck coupling which proves to strongly influence the dynamic response of the body when there is a coincidence between string and neck modal frequencies. The inclusion of geometrical nonlinearities proves to be of major importance, even for a weak plucking, as it allows qualitative representation of double frequency terms in the simulations. Overall, physical simulations of the soundboard motion are in good agreement with measurements indicating characteristic features of the instrument are captured.


Retarding Ostwald Ripening to Directly Cast 3D Porous Graphene Oxide Bulks at Open Ambient Conditions.
Graphene aerogels (GAs) with attractive properties have shown tremendous potentials in energy- and environment-related applications. Unfortunately, current assembly methods for GAs such as sol-gel and freeze-casting processes must be conducted in enclosed spaces with unconventional conditions, thus being literally inoperative for in situ and continuous productions. Herein, a direct slurry-casting method at open ambient conditions is established to arbitrarily prepare three-dimensional (3D) porous graphene oxide (GO) bulks without macroscopic dimension limits on a wide range of solid surfaces by retarding Ostwald ripening of 3D liquid GO foams when being dried in air. A subsequent fast thermal reduction (FTR) of GO foams leads to the formation of graphene aerogels (denoted as FTR-GAs) with hierarchical closed-cellular graphene structures. The FTR-GAs show outstanding high-temperature thermal insulation (70% decrease for 400 °C), as well as superelasticity (>1000 compression-recovery cycles at 50% strain), ultralow density (10-28 mg cm-3), large specific surface area (BET, 206.8 m2 g-1), and high conductivity (ca. 100 S m-1). This work provides a viable method to achieve in situ preparations of high-performance GAs as multifunctional structural materials in aircrafts, high-speed trains, or even buildings for the targets of energy efficiency, comfort, and safety.


Three-dimensional finite element analysis of zirconia all-ceramic cantilevered fixed partial dentures with different framework designs.
The purpose of this study were: to perform stress analyses using three-dimensional finite element analysis methods; to analyze the mechanical stress of different framework designs; and to investigate framework designs that will provide for the long-term stability of both cantilevered fixed partial dentures (FPDs) and abutment teeth. An analysis model was prepared for three units of cantilevered FPDs that assume a missing mandibular first molar. Four types of framework design (Design 1, basic type; Design 2, framework width expanded buccolingually by 2 mm; Design 3, framework height expanded by 0.5 mm to the occlusal surface side from the end abutment to the connector area; and Design 4, a combination of Designs 2 and 3) were created. Two types of framework material (yttrium-oxide partially stabilized zirconia and a high precious noble metal gold alloy) and two types of abutment material (dentin and brass) were used. In the framework designs, Design 1 exhibited the highest maximum principal stress value for both zirconia and gold alloy. In the abutment tooth, Design 3 exhibited the highest maximum principal stress value for all abutment teeth. In the present study, Design 4 (the design with expanded framework height and framework width) could contribute to preventing the concentration of stress and protecting abutment teeth.


A rare vascular anomaly in the form of double left brachiocephalic vein detected incidentally during cardiac implantable electronic device (CIED) placement.
The growing number of transvenous cardiac implantable electronic device (CIED) implantation procedures helps detect rare vascular anomalies. Genetic disturbances in vascular development can produce systemic vein anomalies, including the left brachiocephalic vein (BCV). BCV anomalies commonly coexist with a persistent left superior vena cava (PLSVC), detected in 0.3-0.5% of the general population. The three known anatomical variations of PLSVC are two variations involving a BCV bridge and the third with BCV agenesis. BCV anomalies occur in 1% of patients with congenital heart defects, whereas the estimated proportion of BCV anomalies in the population with no cardiovascular symptoms is below 0.4%. A rarely observed, and thus rarely reported, BCV variation is a double left BCV, with the additional vessel typically found inferior and posterior to the ascending aorta prior to draining into the superior vena cava. This case report presents a previously unreported variation of double left BCV, with both vessels coursing parallel to each other, superior to the aortic arch. (Folia Morphol 2018; 77, 1: 161-165).


A conceptual model for translating omic data into clinical action.
Genomic, proteomic, epigenomic, and other "omic" data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called "the omic funnel." This model parallels the classic "Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice.


Genetically engineered mouse melanoma and mouse Lewis lung carcinoma models.
Melanoma B16-F10 cells and Lewis lung carcinoma LL/2 cells were engineered with a bacterial gene -- chloramphenicol acetyl transferase (CAT) -- by establishing stable transductants. Expression of CAT in both cell types did not alter the ability of these cells to grow into tumors when injected subcutaneously into mice. In addition, the measurement of CAT levels in the lung using a simple ELISA assay revealed a close correlation with direct counting of metastatic nodules. Thus, the CAT-expressing cells will likely have wide ranging applications to quantify tumor metastasis especially in situations where visual counting is difficult. The availability of genetically labeled mouse B16-F10 melanoma and Lewis lung carcinoma cell lines will facilitate future studies of the mechanism and progression of cancer and the discovery of new therapies.


Paeoniflorin Protects H9c2 Cardiomyocytes against Hypoxia/Reoxygenation Induced Injury via Regulating the AMPK/Nrf2 Signaling Pathway.
Myocardial ischemia/reperfusion (MIR) injury contributes to the exacerbation of heart disease by causing cardiac arrhythmias, myocardial infarction, and even sudden death. Studies have found that paeoniflorin (PF) has a protective effect on coronary artery disease (CAD). However, the mechanism of PF in MIR has not been fully investigated. The purpose of this study was to investigate the functional role of PF in H9c2 cells subjected to hypoxia/reoxygenation (H/R). Here, PF treatment enhanced cell viability in H/R-stimulated H9c2 cells. In H9c2 cells, PF treatment reduced the formation of reactive oxygen species (ROS) induced by H/R. In H/R-stimulated H9c2 cells, PF also increased the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Furthermore, PF protected H9c2 cells against H/R-induced apoptosis, as demonstrated by increased Bcl-2 expression, decreased Bax expression, and decreased caspase-3 activity. Furthermore, PF increased the levels of p-AMPK and nuclear Nrf2 expression in response to H/R stimulation. AMPK inhibition, on the other hand, abolished the PF-mediated increase in Nrf2 signaling and the cardiac-protective effect in H9c2 cells exposed to H/R. These data suggest that PF protected H9c2 cells against H/R-induced oxidative stress and apoptosis through modulating the AMPK/Nrf2 signaling pathway. Our findings support the therapeutic potential of PF in myocardial I/R damage.


American Board of Health Physics: the first 35 years.
1994 marked the 35th Anniversary of the founding of the American Board of Health Physics (ABHP) by the Health Physics Society. This paper attempts to identify the major elements in the evolution of the ABHP and, where possible, the individual(s) responsible through 1993. Areas discussed include the implementation of the ABHP by the first few Boards, the duties of the examination panels, the evolution of the various examinations, the development of the recertification program, the economic factors in ABHP operations, and the birth of the American Academy of Health Physics.


Moral consensus theory: paradigm cases of abortion and orthothanasia in Brazil.
Bioethics is a relatively new way of thinking about relationships in medical practice. It enables reflection on ethical conflicts, and opens up management options without dictating rules. Despite this historical context, medical ethics has been sidelined in the course of the development of bioethics. Bioethical reflection does not automatically result in changes to conflict resolution in daily doctor-patient relationships. However, these reflections are important because they promote the search for a "moral consensus" that establishes new ethical rules for day-to-day medical practice. We suggest that there is no conflict between bioethics and medical ethics; rather, these areas interact to establish new standards of behaviour among physicians. The legalisation of orthothanasia in Brazil is one example of how this theory of moral consensus might operate. On the other hand, the legal battle on abortion illustrates how the law cannot change without such a moral consensus.


Molecular Virology of SARS-CoV-2 and Related Coronaviruses.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global COVID-19 pandemic continues to threaten the lives of hundreds of millions of people, with a severe negative impact on the global economy. Although several COVID-19 vaccines are currently being administered, none of them is 100% effective. Moreover, SARS-CoV-2 variants remain an important worldwide public health issue. Hence, the accelerated development of efficacious antiviral agents is urgently needed. Coronavirus depends on various host cell factors for replication. An ongoing research objective is the identification of host factors that could be exploited as targets for drugs and compounds effective against SARS-CoV-2. In the present review, we discuss the molecular mechanisms of SARS-CoV-2 and related coronaviruses, focusing on the host factors or pathways involved in SARS-CoV-2 replication that have been identified by genome-wide CRISPR screening.


Sustainability as an Intrinsic Moral Concern for Solidaristic Health Care.
Environmental pollution and greenhouse gas emissions that contribute to climate change have adverse impacts on global health. Somewhat paradoxically, health care systems that aim to prevent and cure disease are themselves major emitters and polluters. In this paper we develop a justification for the claim that solidaristic health care systems should include sustainability as one of the criteria for determining which health interventions are made available or reimbursed - and which not. There is however a complication: most adverse health effects due to climate change do occur elsewhere in the world. If solidarity would commit us to take care of everyone's health, worldwide, it might imply that solidaristic health system cannot justifiably restrict universal access to their own national populations. In response we explain health solidarity is to be considered as a moral ideal. Such an ideal does not specify what societies owe to whom, but it does have moral implications. We argue that ignoring sustainability in political decision making about what health care is to be offered, would amount to betrayal of the ideal of solidarity.