Bone marrow transplantation for acute myeloblastic leukemia.
Fifty-seven patients with end-stage acute myeloblastic leukemia (AML) received a total of 65 bone marrow transplants between 1968 and 1976. Marrow from HLA genotypically identical allogeneic donors was administered to 32 patients, 13 received marrow from HLA-incompatible donors, donor-recipient HLA compatibility was undetermined for eight patients, and identical twins were marrow donors for four patients. None of the patients in the three latter groups survived beyond 9.4 months after transplantation. Two patients treated with marrow transplants from HLA-compatible donors currently are alive and free of leukemia with functioning grafts 13 and 38 months after transplantation. The 32 patients in the Registry series who received marrow from HLA-compatible donors were compared with a similar series of 46 patients in Seattle. Data for these 78 patients were pooled and analyzed for pretransplant factors that might have prognostic value. Patients with end-stage AML had approximately a 10% chance of surviving 20 months after high-dose chemoradiotherapy plus marrow transplantation. Patients younger than 21 years had a higher six-month survival rate than patients older than 30 years. Patients in the Registry series who received transplants with HLA-compatible marrow within eight months of diagnosis had a higher survival experience than patients who received transplants later.


Lipid rafts and caveolin-1 are required for invadopodia formation and extracellular matrix degradation by human breast cancer cells.
Invadopodia are ventral membrane protrusions through which invasive cancer cells degrade the extracellular matrix. They are thought to function in the migration of cancer cells through tissue barriers, which is necessary for cancer invasion and metastasis. Although many protein components of invadopodia have been identified, the organization and the role of membrane lipids in invadopodia are not well understood. In this study, the role of lipid rafts, which are cholesterol-enriched membrane microdomains, in the assembly and function of invadopodia in human breast cancer cells was investigated. Lipid rafts are enriched, internalized, and dynamically trafficked at invadopodia sites. Perturbation of lipid raft formation due to depleting or sequestering membrane cholesterol blocked the invadopodia-mediated degradation of the gelatin matrix. Caveolin-1 (Cav-1), a resident protein of lipid rafts and caveolae, accumulates at invadopodia and colocalizes with the internalized lipid raft membranes. Membrane type 1 matrix metalloproteinase (MT1-MMP), a matrix proteinase associated with invadopodia, is localized at lipid raft-enriched membrane fractions and cotrafficked and colocalized with Cav-1 at invadopodia. The small interfering RNA-mediated silencing of Cav-1 inhibited the invadopodia-mediated and MT1-MMP-dependent degradation of the gelatin matrix. Furthermore, Cav-1 and MT1-MMP are coexpressed in invasive human breast cancer cell lines that have an ability to form invadopodia. These results indicate that invadopodia are the sites where enrichment and trafficking of lipid rafts occur and that Cav-1 is an essential regulator of MT1-MMP function and invadopodia-mediated breast cancer cell invasion.


Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006.
The increasing incidence of thyroid cancer in the United States is well documented. In this study, we assessed the incidence patterns by histologic type according to demographic and tumor characteristics to further our understanding of these cancers. We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed during 1992-2006 to investigate patterns for the four major histologic types of thyroid cancer by gender, race/ethnicity, and age as well as registry, tumor stage, and size. Among women, papillary thyroid cancer rates were highest among Asians (10.96 per 100,000 woman-years) and lowest among blacks (4.90 per 100,000 woman-years); follicular cancer rates did not vary substantially by race/ethnicity (p-values >0.05), medullary cancer rates were highest among Hispanics (0.21 per 100,000 woman-years) and whites (0.22 per 100,000 woman-years), and anaplastic rates were highest among Hispanics (0.17 per 100,000 woman-years). Among men, both papillary and follicular thyroid cancer rates were highest among whites (3.58 and 0.58 per 100,000 man-years, respectively), medullary cancer rates were highest among Hispanics (0.18 per 100,000 man-years), and anaplastic rates were highest among Asians (0.11 per 100,000 man-years). Racial/ethnic-specific rates did not vary notably across registries. In contrast to age-specific rates of papillary thyroid cancer that peaked in midlife (age 50), especially pronounced among women, rates for follicular, medullary, and anaplastic types continued to rise across virtually the entire age range, especially for anaplastic carcinomas. Female-to-male incidence rate ratios among whites decreased with age most steeply for the follicular type and least steeply for the medullary type; it was <1 until the very oldest ages for the anaplastic type. We conclude that the similar age-specific patterns and lack of geographical variation across the SEER racial/ethnic groups indicate that detection effects cannot completely explain the observed thyroid cancer incidence patterns as variation in the amount or quality of healthcare provided has been shown to vary by SEER racial/ethnic groups, gender, and age. We find that the variations in age-specific patterns by gender and across histologic types are intriguing and recommend that future etiologic investigation focus on exogenous and endogenous exposures that are experienced similarly by racial/ethnic groups, more strongly among women, and distinctively by age.


Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility.
Reproductive diseases have become a growing worldwide problem and male factor plays an important role in the reproductive diagnosis, prognosis and design of assisted reproductive treatments. Sperm cell holds the mission of carrying the paternal genetic complement to the oocyte in order to contribute to an euploid zygote with proper DNA integrity. Sperm DNA fragmentation had been used for decades as a male fertility test, however, its usefulness have arisen multiple debates, especially around Intracytoplasmic Sperm Injection (ICSI) treatments. In the recent years, it has been described that different types of sperm DNA breaks (single and double strand DNA breaks) cause different clinical reproductive effects. On one hand, single-strand DNA breaks are present extensively as a multiple break points in all regions of the genome, are related to oxidative stress and cause a lack of clinical pregnancy or an increase of the conception time. On the other hand, double-strand DNA breaks are mainly localized and attached to the sperm nuclear matrix as a very few break points, are possibly related to a lack of DNA repair in meiosis and cause a higher risk of miscarriage, low embryo quality and higher risk of implantation failure in ICSI cycles. The present work also reviews different studies that may contribute in the understanding of sperm chromatin as well as treatments to prevent sperm DNA damage.


Synthesis and pharmacological studies of new pyrazole analogues of podophyllotoxin.
The pyrazole analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability ofthe chemicals. Initially, benzylide-neacetophenones (chalcones) were prepared in high yields by Claisen-Schmidt reaction of acetophenones with 4-(methylthio)benzaldehyde. The cyclopropyl ketones were prepared in good yields by the reaction of chalcones with trimethylsulfoxonium iodide. Tetralones were prepared in good yields by the Friedel-Craft's intramolecular cyclization reaction of cyclopropyle ketones in the presence of anhyd. stannic chloride and acetic anhydride. The tetralones on formylation to give substituted hydroxylmethylene tetralones. Condensation of substituted hydroxylmethylene tetralones with hydrazine hydrate afforded target compounds. The structures of the synthesized compounds were confirmed by IR, 'H-NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities. Among the synthesized compounds cyclopropyl ketones and pyrazole analogues of podophyllotoxin, compound 7-(Methytthio)-5-(4-(methylthio)phe- nyl)-4,5.-dihydro-2H-benzo[g]indazole is more active than 5-(4-(Methylthio)phenyl)-4,5-dihydro-2H-ben- zo[g]indazole, 7-Methyl-5-(4-(methylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole, 7-Methoxy-5-(4-(meth- ylthio)phenyl)-4,5-dihydro-2H-benzo[g]indazole and the key intermediate tetralones in 100, 200 and 400 ppm at 12, 18 and 24 hrs and also showed very good activity against screened bacteria and fungi compared to their standard.


Differences in total mitochondrial proteins and proteins synthesized by mitochondria from rat liver and Morris hepatomas 9618A, 5123C, and 5123tc.
Mitochondria were isolated from a slow-growing (9618A) and two intermediate-to-fast-growing (5123C, 5123tc) Morris hepatomas and host livers. The mitochondrial proteins were solubilized and fractionated on sodium dodecyl sulfate:polyacrylamide slab gels. One Coomassie blue-stained band was absent or reduced in amount in all tumors relative to host livers. In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects. Incubation of mitochondria with [35S]methionine and a suitable amino acid incorporation system resulted in labeling of specific mitochondrial proteins. Autoradiography of the slab gels disclosed four prominently labeled fractions and a number of minor fractions. Preparations from hepatoma 5123tc demonstrated two labeled bands that were absent or greatly reduced in host liver. Host liver preparations displayed a minor band that was absent or greatly reduced in hepatoma 5123C. However, no single change in labeling pattern was common to all three tumors, suggesting the absence of a causal relationship between carcinogenesis and mutations in mitochondrial DNA.


pH clock-operated mechanized nanoparticles.
Mechanized nanoparticles (MNPs) consisting of supramolecular machines attached to the surface of mesoporous silica nanoparticles are designed to release encapsulated guest molecules controllably under pH activation. The molecular machines are comprised of cucurbit[6]uril (CB[6]) rings that encircle tethered trisammonium stalks and can be tuned to respond under specific pH conditions through chemical modification of the stalks. Luminescence spectroscopy demonstrates that the MNPs are able to contain guest molecules within nanopores at neutral pH levels and then release them once the pH is lowered or raised.


Derivation of a No significant risk level (NSRL) for acrylamide.
Acrylamide is included on the State of California's Proposition 65 list as a carcinogen. Acrylamide is found in cigarette smoke and in many types of foods, including breads, cereals, coffee, cookies, French fries, and potato chips. In 1990, California's Office of Environmental Health Hazard Assessment (OEHHA) established a no significant risk level (NSRL) of 0.2 μg/day for acrylamide. Since then, multiple cancer studies have been published. In this report, we developed an updated NSRL for acrylamide. Using benchmark dose modeling and a weight-of-evidence, non-threshold approach to identify the most sensitive species, cancer slope factors (CSFs) were derived based on combined incidences of statistically significant neoplastic lesions in the Harderian gland, lung, and stomach in male mice. We then used a toxicokinetic (TK)-based scaling approach to convert the animal CSF to a human equivalent CSF, which served as the basis for the NSRL of 1.1 μg/day at the cancer risk level of 1 in 100,000. This NSRL can be used in quantitative exposure assessments to assess compliance with Proposition 65 to ascertain either the need for or exemption from the Proposition 65 labeling requirement and drinking water discharge prohibition.


Dendrimers in drug research.
Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.


[Neurological and psychiatric symptoms in patients with systemic lupus erythematosus].
Sixty patients (51 women/9 men) with diagnosis of SLE were studied for finding out the frequency of nervous system involvement in SLE, the time of of appearance of neurological involvement after diagnosis establishing, the coexistence of the antiphospholipid syndrome, and the character of changes in MR, CT and CSF. Nervous system involvement was found in 40 cases (67%), with 34 cases (56%) had involvement of the CNS, 6 patients (10%) had symptoms of peripheral nervous system dysfunction, and 3 (5%) had involvement of both systems. In 4 cases polineuropathy and transverse spinal cord lesion, and in 3 cases psychiatric symptoms were the first manifestations of SLE. Changes due to involvement of cerebral vessels (TIA, stroke) were observed in 20 patients (33%), and psychiatric symptoms in 16 cases (26.6%). No difference was found in the occurrence of stroke or TIA between SLE patients with and without antiphospholipid syndrome, and no correlations were noted between the presence of neurological or psychiatric symptoms and other SLE symptoms. CT scans demonstrated corticosubcortical atrophy in 28.3% of cases, while in MRI in T2 images small hyperintense lesions were situated mainly in the white matter (33.9%). In 5 cases oligoclonal band was found in the CSF, but without any correlation with specific neurological symptoms.


2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside suppresses human colorectal cancer cell metastasis through inhibiting NF-κB activation.
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a major component of Polygonum multiflorum Thunb (He-Shou-Wu), has been reported to exhibit antioxidant and anti-inflammatory effects. However, its anti-metastatic effect against colorectal cancer is still unclear. In this study, cell migration, invasion and adhesion abilities as well as metastasis-associated protein and NF-κB pathway signaling factor expression were analyzed after treating HT-29 cells with THSG. According to the results, the migration and invasiveness of HT-29 cells were reduced after treatment with 5 or 10 mM THSG (p<0.05). Additionally, the levels of matrix metalloproteinase-2 (MMP-2) and phosphorylated VE-cadherin in HT-29 cells were reduced and the transepithelial electrical resistance (TEER) of EA.hy926 endothelial cell monolayers was increased after incubation in THSG for 24 h (p<0.05). Cell adhesion ability and the E-selectin and intercellular adhesion molecule-1 (ICAM-1) protein levels were reduced when EA.hy926 endothelial cells were treated with THSG (p<0.05). In addition, the cytoplasmic phosphorylation of IκB, the nuclear p65 level and the DNA-binding activity of NF-κB were reduced after treating HT-29 or EA.hy926 cells with 5 or 10 mM THSG (p<0.05). These results suggest that THSG inhibits HT-29 cell metastasis by suppressing cell migration, invasion and adhesion. Furthermore, THSG inhibits metastasis-associated protein expression by suppressing NF-κB pathway activation.


Two experiments on the spectral boundary conditions for nonlinear additivity of simultaneous masking.
The present paper describes the results from two experiments which explored the spectral boundaries for the nonlinear additivity of simultaneous masking. The first experiment measured the threshold for detection of a 2-kHz tone in the presence of two 800-Hz-wide bands of noise that had varying degrees of spectral overlap with each other and the 2-kHz signal. Results revealed an abrupt transition from linear to nonlinear additivity of masking as the spectral separation between the two maskers varied from some overlap to none. The second experiment examined alternative explanations for the data. Explanations based on restricted-listening or distortion-product-detection hypotheses were not supported by the results of this experiment. These data indicate that nonlinear additivity of simultaneous masking holds for maskers that do not overlap within the critical band centered on the signal frequency. This interpretation is also consistent with a large body of data on the monaural and binaural summation (additivity) of loudness.


Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation.
Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection. Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets. Patient enrolment was based on acceptance for transplantation determined by donor lymphocyte crossmatch results. Donor-reactive AECA were found in 35 of 147 (24%) patients. A significantly higher proportion of patients with a positive ECXM had rejections (16 of 35, 46%) during the follow-up of at least 3 months compared with those without AECA (13 of 112, 12%; P<0.00005). Both IgG and IgM AECAs were associated with graft rejections. Mean serum creatinine levels were significantly higher in patients with a positive ECXM test at 3 and 6 months posttransplant. XM-ONE is quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte crossmatches.


Photoionization and core resonances from range-separated time-dependent density-functional theory for open-shell states: Example of the lithium atom.
We consider the calculations of photoionization spectra and core resonances of open-shell systems using range-separated time-dependent density-functional theory. Specifically, we use the time-dependent range-separated hybrid (TDRSH) scheme, combining a long-range Hartree-Fock exchange potential and kernel with a short-range potential and kernel from a local density-functional approximation, and the time-dependent locally range-separated hybrid (TDLRSH) scheme, which uses a local range-separation parameter. To efficiently perform the calculations, we formulate a spin-unrestricted linear-response Sternheimer approach in a non-orthogonal B-spline basis set using appropriate frequency-dependent boundary conditions. We illustrate this approach on the Li atom, which suggests that TDRSH and TDLRSH are adequate simple methods for estimating the single-electron photoionization spectra of open-shell systems.


Psoriatic onycho-periostitis. Report of three cases.
Authors report three cases of psoriatic onycho-periostitis (great toe in two cases, thumb in one case). In a recent study, they demonstrated that osteoperiostitis of the distal phalanx of the great toe was significantly more frequent in patients with psoriatic arthritis than in other groups (cutaneous psoriasis, rheumatoid arthritis, spondylarthropathy, connective tissue diseases, and control subjects), suggesting that the existence of osteoperiostitis of the distal phalanx of the great toe is valuable for the diagnosis of psoriatic arthropathy.


Impact of permanent pacemaker on mortality after transcatheter aortic valve implantation: the PRAGMATIC (Pooled Rotterdam-Milan-Toulouse in Collaboration) Pacemaker substudy.
We sought to evaluate the impact of permanent pacemaker (PPM) implantation on two-year mortality and one-year left ventricular ejection fraction recovery (∆LVEFR=one-year LVEF-baseline LVEF) after transcatheter aortic valve implantation (TAVI). We pooled patient-level data from four European institutions with significant TAVI volume. Outcomes were compared between patients without PPM (no-PPM), patients with PPM prior to TAVI (old-PPM) and patients with PPM implanted after TAVI (new-PPM). Out of 1,062 patients included in the pooled data set, 783 (73.7%) were in the no-PPM group, 164 (15.4%) in the new-PPM group and 115 (10.8%) in the old-PPM group. All-cause and cardiovascular mortality at two years were similar for patients with no-PPM and new-PPM (adjusted HR 1.11, 95% CI: 0.74-1.67; p=0.62; and adjusted HR 1.16, 95% CI: 0.68-1.98; p=0.59). Conversely, old-PPM was associated with increased risk of both all-cause and cardiovascular mortality vs. no-PPM. By multivariable analysis new-PPM did not affect LVEFR, while old-PPM did. We observed a multiplicative interaction, between new-PPM and post-procedural aortic regurgitation ≥1+ on two-year mortality and one-year LVEFR, with increased risk of death and impaired LVEFR in patients with new-PPM and post-procedural aortic regurgitation (PPAR) ≥1+ (both pinteraction<0.0001). In patients undergoing TAVI, the presence of a PPM at baseline yielded a negative effect on long-term prognosis while new-PPM did not. The combination of new-PPM with PPAR adversely impacts on survival and LV function recovery.


Genomics and conservation units: The genetic basis of adult migration timing in Pacific salmonids.
It is now routinely possible to generate genomics-scale datasets for nonmodel species; however, many questions remain about how best to use these data for conservation and management. Some recent genomics studies of anadromous Pacific salmonids have reported a strong association between alleles at one or a very few genes and a key life history trait (adult migration timing) that has played an important role in defining conservation units. Publication of these results has already spurred a legal challenge to the existing framework for managing these species, which was developed under the paradigm that most phenotypic traits are controlled by many genes of small effect, and that parallel evolution of life history traits is common. But what if a key life history trait can only be expressed if a specific allele is present? Does the current framework need to be modified to account for the new genomics results, as some now propose? Although this real-world example focuses on Pacific salmonids, the issues regarding how genomics can inform us about the genetic basis of phenotypic traits, and what that means for applied conservation, are much more general. In this perspective, we consider these issues and outline a general process that can be used to help generate the types of additional information that would be needed to make informed decisions about the adequacy of existing conservation and management frameworks.


Late effects of poliomyelitis.
Muscular atrophy and decreased functional abilities are recognized as late complications of poliomyelitis. This study sought to more clearly define late-onset, postpolio muscular weakness--age of onset, symptoms, and severity--and to determine whether people might benefit from environmental modification, respiratory aids, and orthoses. A total of 183 postpolio patients were examined by a physician and completed a questionnaire on their ambulatory status and related musculoskeletal and respiratory symptoms. Of those participating in the study, 154 claimed to be experiencing late deterioration in strength. The syndrome included decreased endurance, more limited ambulation, and increased weakness in the previously affected limb/s. For those describing late-onset weakness, average ages were determined for the onset of polio (8.3 years), the onset of postpolio muscular weakness (42.3 years), and the latent period of stable functioning (34.8 years). Patients claimed to have experienced a new, lower level of strength for an average of 4.7 years. All 33 patients who had undergone muscle transfer surgery were experiencing late-onset weakness in that extremity. Fasciculations (51%) and long-bone fractures secondary to falls (21%) were common sleep disturbances occurred frequently (31%) even in those without prior bulbar involvement. Upper motor neuron signs were present in only one case. Bracing was rare (16%) and the braces used were usually old. The subjects did not report a steadily or rapidly progressive decline, but rather described a steplike decrement with long plateaus. The population described losses in strength that had significant bearing on functional status and general health.(ABSTRACT TRUNCATED AT 250 WORDS)


Integrated Label-Free and 10-Plex DiLeu Isobaric Tag Quantitative Methods for Profiling Changes in the Mouse Hypothalamic Neuropeptidome and Proteome: Assessment of the Impact of the Gut Microbiome.
Gut microbiota can regulate host physiological and pathological status through gut-brain communications or pathways. However, the impact of the gut microbiome on neuropeptides and proteins involved in regulating brain functions and behaviors is still not clearly understood. To address the problem, integrated label-free and 10-plex DiLeu isobaric tag-based quantitative methods were implemented to compare the profiling of neuropeptides and proteins in the hypothalamus of germ-free (GF)- vs conventionally raised (ConvR)-mice. A total of 2943 endogenous peptides from 63 neuropeptide precursors and 3971 proteins in the mouse hypothalamus were identified. Among these 368 significantly changed peptides (fold changes over 1.5 and a p-value of <0.05), 73.6% of the peptides showed higher levels in GF-mice than in ConvR-mice, and 26.4% of the peptides had higher levels in ConvR-mice than in GF-mice. These peptides were mainly from secretogranin-2, phosphatidylethanolamine-binding protein-1, ProSAAS, and proenkephalin-A. A quantitative proteomic analysis employing DiLeu isobaric tags revealed that 282 proteins were significantly up- or down-regulated (fold changes over 1.2 and a p-value of <0.05) among the 3277 quantified proteins. These neuropeptides and proteins were mainly involved in regulating behaviors, transmitter release, signaling pathways, and synapses. Interestingly, pathways including long-term potentiation, long-term depression, and circadian entrainment were involved. In the present study, a combined label-free and 10-plex DiLeu-based quantitative method enabled a comprehensive profiling of gut microbiome-induced dynamic changes of neuropeptides and proteins in the hypothalamus, suggesting that the gut microbiome might mediate a range of behavioral changes, brain development, and learning and memory through these neuropeptides and proteins.


Microfluidic adhesion induced by subsurface microstructures.
Natural adhesives in the feet of different arthropods and vertebrates show strong adhesion as well as excellent reusability. Whereas the hierarchical structures on the surface are known to have a substantial effect on adhesion, the role of subsurface structures such as the network of microchannels has not been studied. Inspired by these bioadhesives, we generated elastomeric layers with embedded air- or oil-filled microchannels. These adhesives showed remarkable enhancement of adhesion ( approximately 30 times), which results from the crack-arresting properties of the microchannels, together with the surface stresses caused by the capillary force. The importance of the thickness of the adhesive layer, channel diameter, interchannel spacing, and vertical position within the adhesive has been examined for developing an optimal design of this microfluidic adhesive.


[Effects of intravenous administration of clarithromycin on plasma levels of gastrin and group I pepsinogen].
Erythromycin and some of its derivatives have prokinetic gastrointestinal properties. In addition, erythromycin has been shown to stimulate isolated chief cells of the gastric mucosa, and to activate pepsin secretion. The above study was aimed at ascertaining in a group of dyspeptic patients whether clarithromycin, a structural analogue of erythromycin, is apt to modify certain functional parameters of gastric secretion, above all the patterns of gastrin and PG-I secretion. A 20-minute intravenous clarithromycin infusion (1.5 mg/kg) in fasting subjects has brought about a significant reduction (at 20 and 45 minutes from the start of infusion) of circulating gastrin (about 23%) and, after a meal, a 69% increase. No change of plasma PG-I level was observed either after placebo or after the active substance. These findings suggest that in vivo and at the doses used in our experiment clarithromycin has no influence on plasma PG-I release and is apt to modify the fasting and postprandial gastrin releasing pattern.


Public trust in the Government to control the spread of COVID-19 in England after the first wave-a longitudinal analysis.
To control the spread of coronavirus disease 2019 (COVID-19), governments are increasingly relying on the public to voluntarily manage risk. Effectiveness is likely to rely in part on how much the public trusts the Government's response. We examined the English public's trust in the Conservative Government to control the spread of COVID-19 after the initial 'crisis' period. We analyzed eight rounds of a longitudinal survey of 1899 smartphone users aged 18-79 in England between October 2020 and December 2021. We fitted a random-effects logit model to identify personal characteristics and opinions associated with trust in the Conservative Government to control the spread of COVID-19. Trust was lowest in January 2021 (28%) and highest in March 2021 (44%). Being older, having lower educational attainment and aligning with the Conservative Party were predictors of higher levels of trust. Conversely, being less deprived, reporting that Government communications were not clear and considering that the measures taken by the Government went too far or not far enough were predictors of being less likely to report a great deal or a fair amount of trust in the Government to control the pandemic. Trust in the Government's response was found to be low throughout the study. Our findings suggest that there may be scope to avoid losing trust by aligning Government actions more closely with scientific advice and public opinion, and through clearer public health messaging. However, it remains unclear whether and how higher trust in the Government's response would increase compliance with Government advice.


Initiation of pharmacological therapy in Parkinson's disease: when, why, and how.
Debate is ongoing regarding when, why, and how to initiate pharmacotherapy for Parkinson's disease. Early initiation of dopaminergic therapies does not convey disease-modifying effects but does reduce disability. Concerns about the development of motor complications arising from the early initiation of levodopa, which led to misconceived levodopa-sparing strategies, have been largely mitigated by the outcomes of the PD MED and Levodopa in Early Parkinson's Disease (LEAP) studies. The LEAP study also showed the potential for early improvement in quality of life, even when disability is negligible. Until more effective methods of providing stable dopamine concentrations are developed, current evidence supports the use of levodopa as initial symptomatic treatment in most patients with Parkinson's disease, starting with low doses and titrating to therapeutic threshold. Monoamine oxidase-B inhibitors and dopamine agonists can be reserved as potential adjunct treatments later in the disease course. Future research will need to establish effective disease-modifying treatments, address whether patients' quality of life is substantially improved with early initiation of treatment rather than a wait and watch strategy, and establish whether new levodopa formulations will delay onset of dyskinesia.


Improved antifouling properties of photobioreactors by surface grafted sulfobetaine polymers.
To improve the antifouling (AF) properties of photobioreactors (PBR) for microalgal cultivation, using trihydroxymethyl aminomethane (tris) as the linking agent, a series of polyethylene (PE) films grafted with sulfobetaine (PE-SBMA) with grafting density ranging from 23.11 to 112 μg cm-2 were prepared through surface-initiated atom transfer radical polymerization (SI-ATRP). It was found that the contact angle of PE-SBMA films decreased with the increase in the grafting density. When the grafting density was 101.33 μg cm-2, it reached 67.27°. Compared with the PE film, the adsorption of protein on the PE-SBMA film decreased by 79.84% and the total weight of solid and absorbed microalgae decreased by 54.58 and 81.69%, respectively. Moreover, the transmittance of PE-SBMA film recovered to 86.03% of the initial value after cleaning, while that of the PE film recovered to only 47.27%. The results demonstrate that the AF properties of PE films were greatly improved on polySBMA-grafted surfaces.


[A comparism between lysosomal enzyme activity in normal ectocervical squamous epithelium and squamous carcinoma of the ectocervix].
A comparative study was made of the total lysosomal enzyme activity found in homogenates of normal ectocervical squamous epithelium and squamous carcinoma of this epithelium. The activities of acid phosphatase, beta-glucuronidase, cathepsin D and acid ribonuclease were higher in carcinoma tissue than in normal tissue. The most important observation made was with regard to the distribution of enzyme activity in homogenates. In carcinoma homogenates most of the enzyme activity was detected in the lysosomal fractions, whereas in controls the activity was predominantly found in the cytosol fractions. No histochemical and electron microscopical techniques were used in this study. Because it was possible to sediment the enzyme activity and to demonstrate latency, these can be referred to as lysosomal enzymes with certainty.


Do insecticide-treated bednets have an effect on malaria vectors?
The use of insecticide-treated bednets (ITNs) has been widely adopted as an important method for malaria control. Few data exist on effects of ITNs on mosquito biology and ecology, other than the development of insecticide resistance against the insecticides used. There is no hard evidence that the insecticide resistance recorded is the result of insecticidal use on bednets or from agricultural use. Resistance against pyrethroids, the preferred class of insecticides for ITN use, has been recorded from countries in Asia, Africa and South America. Resistance is expressed as reduced excito-repellency and mortality of mosquitoes exposed to insecticide-treated materials. In the absence of resistance, however, most studies on ITN effects report a reduced survival of adult mosquitoes as well as mass killing. Other effects are highly variable, and shifts in time of biting, feeding site and blood hosts have occasionally been reported, but not in proportion to the scale of ITN use. In general, a reduced sporozoite rate is recorded in ITN programmes. Because many of the anticipated behavioural effects caused by insecticidal use will be avoided by the use of untreated nets, studies on the efficacy of untreated nets are required. Examples are presented in which untreated nets provided a reasonable degree of protection against malaria.


Improved techniques for successful neonatal rat surgery.
Problems encountered in neonatal rat surgery include mortality due to anesthesia and postoperative mortality due to cannibalism or neglect by the dam. We required a method of anesthesia which would enable us to perform complicated, lengthy, recovery eye surgery on day-old rat pups. Because ethical concerns have been raised regarding hypothermia, the currently recommended procedure for anesthesia of newborn rats, we adapted two effective techniques for anesthetizing adult rats for use in neonates. In the first of these methods, halothane was administered via a gas anesthetic machine which allowed for precise regulation of anesthetic levels. The second method employed diluted Innovar-Vet, a neuroleptanalgesic drug combination that is easily administered by injection, with oxygen supplementation. Because each surgical procedure required 30 to 45 minutes and was technically demanding, it was important to minimize the loss of experimental animals due to cannibalism. To accomplish this, we developed an easy, noninvasive method to encourage acceptance of surgically manipulated pups by the dam, which included hand gentling and olfactory conditioning of pregnant females. All pups (63/63) survived eye surgery under halothane anesthesia and of those examined 7 days later, 55/57 (97%) were alive and appeared normal. Of the pups treated with Innovar-Vet, 16/16 (100%) survived anesthesia and all were normal in appearance when examined 7 days later. Our results suggest that using these anesthetic methods coupled with appropriate conditioning of the dam and handling of the pups contribute to successful neonatal rat surgery.


The potential effect of COVID-19-related disruptions on HIV incidence and HIV-related mortality among men who have sex with men in the USA: a modelling study.
During the COVID-19 pandemic, men who have sex with men (MSM) in the USA have reported similar or fewer sexual partners and reduced HIV testing and care access compared with before the pandemic. Pre-exposure prophylaxis (PrEP) use has also declined. We aimed to quantify the potential effect of COVID-19 on HIV incidence and HIV-related mortality among US MSM. We used a calibrated, deterministic, compartmental HIV transmission model for MSM in Baltimore (MD, USA) and available data on COVID-19-related disruptions to HIV services to predict effects of reductions in sexual partners (0%, 25%, 50%), condom use (5%), HIV testing (20%), viral suppression (10%), PrEP initiations (72%), PrEP adherence (9%), and antiretroviral therapy (ART) initiations (50%). In our main analysis, we modelled disruptions due to COVID-19 starting Jan 1, 2020, and lasting 6 months. We estimated the median change in cumulative new HIV infections and HIV-related deaths among MSM over 1 and 5 years, compared with a base case scenario without COVID-19-related disruptions. A 25% reduction in sexual partners for 6 months among MSM in Baltimore, without HIV service changes, could reduce new HIV infections by median 12·2% (95% credible interval 11·7 to 12·8) over 1 year and median 3·0% (2·6 to 3·4) over 5 years. In the absence of changes in sexual behaviour, the 6-month estimated reductions in condom use, HIV testing, viral suppression, PrEP initiations, PrEP adherence, and ART initiations combined are predicted to increase new HIV infections by median 10·5% (5·8 to 16·5) over 1 year, and by median 3·5% (2·1 to 5·4) over 5 years. Disruptions to ART initiations and viral suppression are estimated to substantially increase HIV-related deaths (ART initiations by median 1·7% [0·8 to 3·2], viral suppression by median 9·5% [5·2 to 15·9]) over 1 year, with smaller proportional increases over 5 years. The other individual disruptions (to HIV testing, PrEP and condom use, PrEP initiation, and partner numbers) were estimated to have little effect on HIV-related deaths (<1% change over 1 or 5 years). A 25% reduction in sexual partnerships is estimated to offset the effect of the combined service disruptions on new HIV infections (change over 1 year: median -3·9% [-7·4 to 1·0]; over 5 years: median 0·0% [-0·9 to 1·4]), but not on HIV deaths (change over 1 year: 11·0% [6·2 to 17·7]; over 5 years: 2·6% [1·5 to 4·3]). Maintaining access to ART and adherence support is of the utmost importance to maintain viral suppression and minimise excess HIV-related mortality due to COVID-19 restrictions in the USA, even if disruptions to services are accompanied by reductions in sexual partnerships. National Institutes of Health.


Catch the rainbow: Prognostic factor of sarcoidosis.
Sarcoidosis is a systemic, chronic, inflammatory disease characterized by noncaseating granuloma formations. The fact that the etiopathogenesis of the disease has not been elucidated yet brings it many theories and assumptions. Being a systemic disease and ability to involve many organs and systems, it attracts the attention of physicians from different branches. In addition to lung involvement, skin, eye, heart, and locomotor system involvement is an important clinical finding. Sarcoidosis may present with very different clinical presentations, and therefore, it is one of the important "imitators" in the medical literature. I like sarcoidosis as a "rainbow," it is a disease that contains the characteristics of many diseases. Different clinical, radiological, and laboratory prognostic factors (lupus pernio, chronic uveitis, late-onset disease, chronic hypercalcemia, nephrocalcinosis, Afro-American race, progressive pulmonary sarcoidosis, radiologic Stage 4, bone involvement, neurosarcoidosis, cardiac involvement, and chronic respiratory failure) have been defined in this "rainbow." Early identification of these factors plays an important role in the determination of treatment strategies, morbidity, and mortality of the disease. In this article, clinical, genetic, laboratory, and radiological factors that determine the prognosis of sarcoidosis are discussed in light of the latest data in the literature.


Point-of-care CRP testing in the diagnosis of pneumonia in adults.
Respiratory tract infections (RTI) are among the most common acute conditions leading to GP consultations and to antibiotic prescribing in primary care, even though 70% are viral, and many others are minor self-limiting bacterial infections.1-4 Between 0.5% and 1.1% of adults have community-acquired pneumonia every year in the UK, most of whom are managed in primary care.4,5 The decision to prescribe antibiotics for an acute RTI in primary care is often based on clinical symptoms, which have low sensitivity and specificity, and high inter-observer variability.2,4 In primary care, it is very difficult to differentiate between diagnoses without additional tests.6 Unnecessary antibiotic prescribing may not aid recovery, exposes patients to potential adverse effects, may encourage repeat attendance and contributes to antibiotic resistance.2,7 One strategy aiming to reduce antibiotic prescribing in primary care is the use of biomarkers (e.g. C-reactive protein [CRP]).2 In the correct clinical context (e.g. in previously healthy people, not those with chronic lung disease) and as an adjunct to clinical assessment, a biomarker may help in the management of an RTI.2 In order to be used during the consultation, the results of a biomarker test must be rapidly available (e.g. 'point-of-care' [POC] testing).4 POC testing for CRP has recently been recommended as part of a national clinical guideline on the diagnosis and management of pneumonia.4 Here, we review the rationale for POC CRP testing and its advantages and disadvantages.


The impact of latency on surgical precision and task completion during robotic-assisted remote telepresence surgery.
It has been suggested that robotic-assisted remote telepresence surgery with a signal transmission latency of greater than 300 ms may not be possible. We evaluated the impact of four different latencies of up to 500 ms on task completion and error rate in five surgeons after completion of three different surgical tasks. The surgeons were able to complete all tasks with a latency of 500 ms. However, higher latency was associated with higher error rates and task completion time (TCT). There were significant variations between surgeons and different tasks. Surgeons are able to complete tasks with a signal transmission latency of up to 500 ms. The clinical impact of slower TCT and increased error rates encountered at higher latency needs to be established.


Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells.
The immunomodulatory drug lenalidomide has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), despite a lack of direct cytotoxic effects in vitro The mechanism of lenalidomide efficacy in vivo is thought to occur via a combination of enhanced immune activity and an alteration of tumor cell-microenvironment interactions. We demonstrate in whole blood from patients with CLL that lenalidomide significantly depletes malignant B cells. Lenalidomide also induced production of interleukin-21 (IL21) and its mRNA in T cells from patients with CLL. In addition, lenalidomide enhanced upregulation of functional IL21 receptor (IL21R) on the cell surface and increased receptor mRNA in vitro The in vitro combination of IL21 and lenalidomide enhanced IL21-mediated cytotoxicity toward CLL cells through a variety of mechanisms. We show association of cell death with upregulation of Bid by IL21, enhanced upregulation of Bid by the combination therapy, and diminished Lck and downstream BCR signaling activation of Syk and PLCG2. Collectively, we demonstrated an immune cell-tumor cell interaction through lenalidomide-mediated induction of IL21 and IL21R, with enhanced IL21-mediated cytotoxicity, which provides justification for this combination in clinical trials for patients with CLL. Cancer Immunol Res; 4(8); 698-707. ©2016 AACR.


Cultures of "Clostridium acetobutylicum" from various collections comprise Clostridium acetobutylicum, Clostridium beijerinckii, and two other distinct types based on DNA-DNA reassociation.
The best-known acetone-butanol (solvent)-producing bacterium is the Weizmann organism, Clostridium acetobutylicum, which was used for starch-based industrial fermentation. In the past two decades, cultures of "C. acetobutylicum" from various culture collections have included organisms that were isolated for sugar (molasses)-based industrial solvent production. Recent biochemical and genetic studies have revealed significant differences among some of these "C. acetobutylicum" strains. We used DNA-DNA reassociation to analyze 39 cultures of "C. acetobutylicum" and phenotypically similar organisms from major collections. The results of this study clearly identified four groups intergroup reassociation values of less than 30%. All of the intragroup values except the value for one strain were 68% or more, which supported species status for each group. The C. acetobutylicum group (with ATCC 824 as the type strain) consisted of 17 cultures and had average reassociation values of 10% with the other three groups. All strains of C. acetobutylicum produced riboflavin in milk, and the cultures were bright yellow, which is useful for differentiating this species from the other three groups. The Clostridium beijerinckii group (with VPI 5481 [= ATCC 25752] as the type strain) consisted of 16 cultures and included strains NCIMB 8052 and NCP 270. Strains NCP 262 and NRRL B643 constituted the third group, whereas strain N1-4 ("Clostridium saccharoperbutylacetonicum") and its derivative, strain N1-4081, formed the fourth group. At present, the last two groups are each represented by only one independent strain; definitive descriptions of these two groups as two new or revived species will require further phenotypic characterization, as well as identification of additional strains. C. beijerinckii NCP 270, Clostridium sp. strain NRRL B643, and "C. saccharoperbutylacetonicum" were used in industrial solvent production from molasses, which confirms that the new organisms used for the sugar-based processes are distinct from C. acetobutylicum.


Extended Joint Sparsity Reconstruction for Spatial and Temporal ERT Imaging.
Electrical resistance tomography (ERT) is an imaging technique to recover the conductivity distribution with boundary measurements via attached electrodes. There are a wide range of applications using ERT for image reconstruction or parameter calculation due to high speed data collection, low cost, and the advantages of being non-invasive and portable. Although ERT is considered a high temporal resolution method, a temporally regularized method can greatly enhance such a temporal resolution compared to frame-by-frame reconstruction. In some of the cases, especially in the industrial applications, dynamic movement of an object is critical. In practice, it is desirable for monitoring and controlling the dynamic process. ERT can determine the spatial conductivity distribution based on previous work, and ERT potentially shows good performance in exploiting temporal information as well. Many ERT algorithms reconstruct images frame by frame, which is not optimal and would assume that the target is static during collection of each data frame, which is inconsistent with the real case. Although spatiotemporal-based algorithms can account for the temporal effect of dynamic movement and can generate better results, there is not that much work aimed at analyzing the performance in the time domain. In this paper, we discuss the performance of a novel spatiotemporal total variation (STTV) algorithm in both the spatial and temporal domain, and Temporal One-Step Tikhonov-based algorithms were also employed for comparison. The experimental results show that the STTV has a faster response time for temporal variation of the moving object. This robust time response can contribute to a much better control process which is the main aim of the new generation of process tomography systems.


Sparse representation of electrodermal activity with knowledge-driven dictionaries.
Biometric sensors and portable devices are being increasingly embedded into our everyday life, creating the need for robust physiological models that efficiently represent, analyze, and interpret the acquired signals. We propose a knowledge-driven method to represent electrodermal activity (EDA), a psychophysiological signal linked to stress, affect, and cognitive processing. We build EDA-specific dictionaries that accurately model both the slow varying tonic part and the signal fluctuations, called skin conductance responses (SCR), and use greedy sparse representation techniques to decompose the signal into a small number of atoms from the dictionary. Quantitative evaluation of our method considers signal reconstruction, compression rate, and information retrieval measures, that capture the ability of the model to incorporate the main signal characteristics, such as SCR occurrences. Compared to previous studies fitting a predetermined structure to the signal, results indicate that our approach provides benefits across all aforementioned criteria. This paper demonstrates the ability of appropriate dictionaries along with sparse decomposition methods to reliably represent EDA signals and provides a foundation for automatic measurement of SCR characteristics and the extraction of meaningful EDA features.


Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate.
Peroxin 5 (PEX5), the peroxisomal protein shuttling receptor, binds newly synthesized peroxisomal matrix proteins in the cytosol and promotes their translocation across the organelle membrane. During the translocation step, PEX5 itself becomes inserted into the peroxisomal docking/translocation machinery. PEX5 is then monoubiquitinated at a conserved cysteine residue and extracted back into the cytosol in an ATP-dependent manner. We have previously shown that the ubiquitin-PEX5 thioester conjugate (Ub-PEX5) released into the cytosol can be efficiently disrupted by physiological concentrations of glutathione, raising the possibility that a fraction of Ub-PEX5 is nonenzymatically deubiquitinated in vivo. However, data suggesting that Ub-PEX5 is also a target of a deubiquitinase were also obtained in that work. Here, we used an unbiased biochemical approach to identify this enzyme. Our results suggest that ubiquitin-specific protease 9X (USP9X) is by far the most active deubiquitinase acting on Ub-PEX5, both in female rat liver and HeLa cells. We also show that USP9X is an elongated monomeric protein with the capacity to hydrolyze thioester, isopeptide, and peptide bonds. The strategy described here will be useful in identifying deubiquitinases acting on other ubiquitin conjugates.


Actuation of chitosan-aptamer nanobrush borders for pathogen sensing.
We demonstrate a sensing mechanism for rapid detection of Listeria monocytogenes in food samples using the actuation of chitosan-aptamer nanobrush borders. The bio-inspired soft material and sensing strategy mimic natural symbiotic systems, where low levels of bacteria are selectively captured from complex matrices. To engineer this biomimetic system, we first develop reduced graphene oxide/nanoplatinum (rGO-nPt) electrodes, and characterize the fundamental electrochemical behavior in the presence and absence of chitosan nanobrushes during actuation (pH-stimulated osmotic swelling). We then characterize the electrochemical behavior of the nanobrush when receptors (antibodies or DNA aptamers) are conjugated to the surface. Finally, we test various techniques to determine the most efficient capture strategy based on nanobrush actuation, and then apply the biosensors in a food product. Maximum cell capture occurs when aptamers conjugated to the nanobrush bind cells in the extended conformation (pH < 6), followed by impedance measurement in the collapsed nanobrush conformation (pH > 6). The aptamer-nanobrush hybrid material was more efficient than the antibody-nanobrush material, which was likely due to the relatively high adsorption capacity for aptamers. The biomimetic material was used to develop a rapid test (17 min) for selectively detecting L. monocytogenes at concentrations ranging from 9 to 107 CFU mL-1 with no pre-concentration, and in the presence of other Gram-positive cells (Listeria innocua and Staphylococcus aureus). Use of this bio-inspired material is among the most efficient for L. monocytogenes sensing to date, and does not require sample pretreatment, making nanobrush borders a promising new material for rapid pathogen detection in food.


A comparison of single-dose caudal clonidine, morphine, or hydromorphone combined with ropivacaine in pediatric patients undergoing ureteral reimplantation.
Caudal blockade is a common technique for pediatric postoperative analgesia. While safe and effective, caudal opioids are associated with troublesome side effects. Caudal clonidine may offer significant analgesic benefits. We prospectively compared the analgesic, side effect, and rehabilitation profiles of caudal clonidine, hydromorphone, or morphine in a group of 60 pediatric patients undergoing ureteral reimplantation. Patients aged 6 mo to 6 yr were evenly and randomly enrolled in a double-blind manner. Patients received a single caudal dose of 2 mcg/kg of clonidine, 10 mcg/kg of hydromorphone, or 50 mcg/kg of morphine, combined with 1.0 mL/kg of 0.2% ropivacaine with epinephrine. After sevoflurane in oxygen/air anesthesia, all subjects received proxy nurse-controlled analgesia with morphine. Postoperative pain intensity, use of IV morphine, and side effects were assessed during the first 24 h. Oral intake and discharge home were recorded. Caudal clonidine resulted in less postoperative nausea and vomiting (P = 0.01) and pruritus (P = 0.007) than did caudal hydromorphone or caudal morphine. Caudal morphine produced more sustained initial analgesia than did caudal clonidine (P = 0.02). No difference was observed in pain scores, total morphine use, time to first oral intake or discharge home. No postoperative respiratory depression, excessive sedation, hypotension, or bradycardia was identified. Although caudal morphine may result in more sustained initial analgesia, caudal clonidine combined with nurse-controlled analgesia appears to provide comparable analgesia with fewer side effects. Based on these results, the use of caudal clonidine may be superior to caudal opioids after pediatric ureteral reimplantation.


Induction of neurite outgrowth in PC12 cells treated with temperature-controlled repeated thermal stimulation.
To promote the functional restoration of the nervous system following injury, it is necessary to provide optimal extracellular signals that can induce neuronal regenerative activities, particularly neurite formation. This study aimed to examine the regulation of neuritogenesis by temperature-controlled repeated thermal stimulation (TRTS) in rat PC12 pheochromocytoma cells, which can be induced by neurotrophic factors to differentiate into neuron-like cells with elongated neurites. A heating plate was used to apply thermal stimulation, and the correlation of culture medium temperature with varying surface temperature of the heating plate was monitored. Plated PC12 cells were exposed to TRTS at two different temperatures via heating plate (preset surface temperature of the heating plate, 39.5°C or 42°C) in growth or differentiating medium for up to 18 h per day. We then measured the extent of growth, neuritogenesis, or acetylcholine esterase (AChE) activity (a neuronal marker). To analyze the mechanisms underlying the effects of TRTS on these cells, we examined changes in intracellular signaling using the following: tropomyosin-related kinase A inhibitor GW441756; p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; and MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 with its inactive analog, U0124, as a control. While a TRTS of 39.5°C did not decrease the growth rate of cells in the cell growth assay, it did increase the number of neurite-bearing PC12 cells and AChE activity without the addition of other neuritogenesis inducers. Furthermore, U0126, and SB203580, but not U0124 and GW441756, considerably inhibited TRTS-induced neuritogenesis. These results suggest that TRTS can induce neuritogenesis and that participation of both the ERK1/2 and p38 MAPK signaling pathways is required for TRTS-dependent neuritogenesis in PC12 cells. Thus, TRTS may be an effective technique for regenerative neuromedicine.


Non-conventional octameric structure of C-phycocyanin.
C-phycocyanin (CPC), a blue pigment protein, is an indispensable component of giant phycobilisomes, which are light-harvesting antenna complexes in cyanobacteria that transfer energy efficiently to photosystems I and II. X-ray crystallographic and electron microscopy (EM) analyses have revealed the structure of CPC to be a closed toroidal hexamer by assembling two trimers. In this study, the structural characterization of non-conventional octameric CPC is reported for the first time. Analyses of the crystal and cryogenic EM structures of the native CPC from filamentous thermophilic cyanobacterium Thermoleptolyngbya sp. O-77 unexpectedly illustrated the coexistence of conventional hexamer and novel octamer. In addition, an unusual dimeric state, observed via analytical ultracentrifugation, was postulated to be a key intermediate structure in the assemble of the previously unobserved octamer. These observations provide new insights into the assembly processes of CPCs and the mechanism of energy transfer in the light-harvesting complexes.


Clinical relevance of sensitization to lupine in peanut-sensitized adults.
The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness.


Fine-scale spatial genetic structure of an endangered marsh herb, Caldesia grandis (Alismataceae).
The endangered marsh herb, Caldesia grandis, is native to China. We investigated the spatial structure of the genetic variation of three populations of C. grandis using RAPD markers and spatial autocorrelation analysis, based on the method of equal distance interval. A total of 157 individuals were sampled from four patches collected from the region of Hunan and Yunnan Provinces, China. Among the polymorphic bands generated by seven selective primers, polymorphic bands with frequencies ranging from 20 to 80% were used to calculate Moran's I spatial autocorrelation coefficient for each patch. We found significant spatial structure of genetic variation in the three patches in Bei Hai (BH) (patches BH-1 and BH-2) and Guai Hu (GH) (patch GH-1) populations of C. grandis (with significant positive autocorrelation within the short distance class). In contrast, the genetic variation in the Lang Pan Hu (LPH) population (patch LPH-1) was found to be randomly distributed. The different spatial distribution patterns may be attributed to environment differences. These results have implications for the conservation and management of this species, especially for sampling strategies for ex situ conservation.


Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease.
EGFR-mutant lung cancer was first described as a new clinical entity in 2004. Here, we present an update on new controversies and conclusions regarding the disease. This article reviews the clinical implications of EGFR mutations in lung cancer with a focus on epidermal growth factor receptor tyrosine kinase inhibitor resistance. The discovery of EGFR mutations has altered the ways in which we consider and treat non-small-cell lung cancer (NSCLC). Patients whose metastatic tumors harbor EGFR mutations are expected to live longer than 2 years, more than double the previous survival rates for lung cancer. The information presented in this review can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC. Efforts should now concentrate on making EGFR-mutant lung cancer a chronic rather than fatal disease.


Molecular recognition on a cavitand-functionalized silicon surface.
A Si(100) surface featuring molecular recognition properties was obtained by covalent functionalization with a tetraphosphonate cavitand (Tiiii), able to complex positively charged species. Tiiii cavitand was grafted onto the Si by photochemical hydrosilylation together with 1-octene as a spatial spectator. The recognition properties of the Si-Tiiii surface were demonstrated through two independent analytical techniques, namely XPS and fluorescence spectroscopy, during the course of reversible complexation-guest exchange-decomplexation cycles with specifically designed ammonium and pyridinium salts. Control experiments employing a Si(100) surface functionalized with a structurally similar, but complexation inactive, tetrathiophosphonate cavitand (TSiiii) demonstrated no recognition events. This provides evidence for the complexation properties of the Si-Tiiii surface, ruling out the possibility of nonspecific interactions between the substrate and the guests. The residual Si-O(-) terminations on the surface replace the guests' original counterions, thus stabilizing the complex ion pairs. These results represent a further step toward the control of self-assembly of complex supramolecular architectures on surfaces.


From light-scattering measurements to polarizability derivatives in vibrational Raman spectroscopy: the 2ν5 overtone of SF6.
The room-temperature isotropic spectrum of SF6 was recorded at the frequency of the 2ν5 overtone by running high-sensitivity incoherent Raman experiments for two independent polarizations of the incident beam and for gas densities varying from 2 to 27 amagat. Weak yet observable pressure effects were found. A transparent analysis of the Raman cross-section problem along with the first-ever prediction of the value of the mean polarizability second derivative ∂(2)α/∂q5(2) are made and the hitherto underestimated role of the hot bands of SF6 is brought to the wider public. The emergence of an analytic hotband factor is shown whose magnitude is dramatically increased with the order of the overtone and the gas temperature and all the more so upon considering low-frequency molecular vibrations. Our formulas, which in the harmonic approximation are exact, are still applicable to real situations provided certain conditions are fulfilled. For nondegenerated modes, generalization to higher order overtones is made, an issue addressing the much challenging problem of the IR-allowed second overtone bands. The content of this paper is also an invitation towards ab initio derivative-calculations for sulfur hexafluoride, especially given the today's needs in interpreting spectra of significance for greenhouse atmospheric issues.


[Primary retroperitoneal adenocarcinoma].
A rare case is reported of retroperitoneal papillary adenocarcinoma in a 25-year-old female. Two recurrences were observed after surgical and radiation treatment. The tumour became inoperable after the second recurrence. The duration of the disease was somewhat more than 5 years. The attention is drawn to the difficulty of differential diagnosis with a metastasis. The young age and histological structure allow one to regard the tumour disembryogenetic and originating from the embryonal germs of urinary-genital organs or from the intestinal tube.


Scientific rigour in qualitative research--examples from a study of women's health in family practice.
The increase in qualitative research in family medicine raises a demand for critical discussions about design, methods and conclusions. This article shows how scientific claims for truthful findings and neutrality can be assessed. Established concepts such as validity, reliability, objectivity and generalization cannot be used in qualitative research. Alternative criteria for scientific rigour, initially introduced by Lincoln and Guba, are presented: credibility, dependability, confirmability and transferability. These criteria have been applied to a research project, a qualitative study with in-depth interviews with female patients suffering from chronic pain in the locomotor system. The interview data were analysed on the basis of grounded theory. The proposed indicators for scientific rigour were shown to be useful when applied to the research project. Several examples are given. Difficulties in the use of the alternative criteria are also discussed.


In vitro production of new types of hemophilus influenzae.
Two new types of Hemophilus influenzae, Sab and Sad have been produced in vitro. Each exhibits the presence of the type specific polysaccharides of 2 types of E. influenzae within the same cell. In Sab the polysaccharides of types a and b have been demonstrated and in Sad those which characterize types a and d. The Sab and Sad traits are inherited. Sab was produced by the action of DNA-containing extract isolated from type a on either type b cells or Rb cells (non-encapsulated non-type-specific cells derived from type b). Sad cells were formed as a result of the action of the DNA-containing extract isolated from type d on cells intermediate between Rab and Sab cells. DNA-containing extracts isolated from Sab cells have induced the Sab trait in Rd cells with predictable regularity. Evidence has been presented that the hereditary determinant of Sab cells is a new genetic substance with new functions. Therefore, the interaction of the DNA-containing substance from cells of one genetic type with living cells of a genetically different type has produced what appears to be a new individual which differs from each of the cells contributing the differing genetic traits but has at least one trait in common with each. Sab cells derived presumably from a single cell show the appearance of type b cells sometime during the first 7 generations.


Ab initio phase diagrams of Hf-O, Zr-O and Y-O: a comparative study.
We present phase diagrams of binary oxides, Hf-O, Zr-O and Y-O, obtained by ab initio evolutionary simulations, in order to explore possible metastable crystalline suboxide structures which could be quenched during the electroforming processes within the conductive filaments in stoichiometric HfO2, ZrO2 and Y2O3 host materials, in resistive switching devices. We find that, in the range MO-MO2 (where M = Hf, Zr, Y), the most energetically favourable atomic configurations have properties which facilitate the ionic conduction of oxygen. Namely, the calculations reveal that oxygen vacancies tend to order in arrays of one-dimensional channels, along which the migration barrier of anions is much lower than for the stoichiometric hosts. We explore for Hf-O and Zr-O a new set of structural patterns, different from those of the host materials, for which a change of oxygen stoichiometry does not change the underlying structural frame. However, a sufficient change of oxygen stoichiometry drives metallic conductivity in oxygen-deficient compounds, whereas their oxygen-rich counterparts are insulating. In contrast to Hf-O and Zr-O, in the Y-O system we find an atomic structure with metallic conductivity, which has the same structural frame as the stoichiometric Y2O3 host. We believe that this property enables the forming-free resistive switching in Y2O3.


Culture, Social Support, and Diabetes Empowerment Among American Indian Adults Living With Type 2 Diabetes.
OBJECTIVE | Type 2 diabetes represents a major health disparity for many American Indian/Alaska Native (AIAN) communities, in which prevalence rates are more than double that of the general U.S. population. Diabetes is a major indicator for other comorbidities, including the leading cause of death for AIANs (i.e., cardiovascular disease). This study investigated associations between protective factors (social support and cultural factors) and self-reported empowerment to manage illness. DESIGN AND METHODS | Participants were drawn from a random sample of tribal clinic records. Data included results from computer-assisted personal interviews with 192 American Indian adults with a diagnosis of type 2 diabetes living on or near a reservation. Community Research Councils, developed at each of the five partnering Anishinaabe reservations, oversaw protocols and procedures in this community-based participatory research collaboration. RESULTS | Multiple ordinary least squares regression models determined that general social support and diabetes-specific social support are positively related to diabetes empowerment. These associations persisted when both social support measures were added to the model, indicating independent effects of different types of social support. Cultural identity and cultural practices were positively related to diabetes empowerment in bivariate analyses; however, both measures dropped from statistical significance after accounting for all other covariates. An interaction term revealed a moderation effect through which cultural identity amplified the positive relationship between social support and diabetes empowerment. CONCLUSION | Results moderately support policy and risk-reduction efforts aiming at expanding social support networks into multiple domains and reinforcing cultural identity and cultural practices.


Improving Consensus Scoring of Crowdsourced Data Using the Rasch Model: Development and Refinement of a Diagnostic Instrument.
Diabetic retinopathy (DR) is a leading cause of vision loss in working age individuals worldwide. While screening is effective and cost effective, it remains underutilized, and novel methods are needed to increase detection of DR. This clinical validation study compared diagnostic gradings of retinal fundus photographs provided by volunteers on the Amazon Mechanical Turk (AMT) crowdsourcing marketplace with expert-provided gold-standard grading and explored whether determination of the consensus of crowdsourced classifications could be improved beyond a simple majority vote (MV) using regression methods. The aim of our study was to determine whether regression methods could be used to improve the consensus grading of data collected by crowdsourcing. A total of 1200 retinal images of individuals with diabetes mellitus from the Messidor public dataset were posted to AMT. Eligible crowdsourcing workers had at least 500 previously approved tasks with an approval rating of 99% across their prior submitted work. A total of 10 workers were recruited to classify each image as normal or abnormal. If half or more workers judged the image to be abnormal, the MV consensus grade was recorded as abnormal. Rasch analysis was then used to calculate worker ability scores in a random 50% training set, which were then used as weights in a regression model in the remaining 50% test set to determine if a more accurate consensus could be devised. Outcomes of interest were the percent correctly classified images, sensitivity, specificity, and area under the receiver operating characteristic (AUROC) for the consensus grade as compared with the expert grading provided with the dataset. Using MV grading, the consensus was correct in 75.5% of images (906/1200), with 75.5% sensitivity, 75.5% specificity, and an AUROC of 0.75 (95% CI 0.73-0.78). A logistic regression model using Rasch-weighted individual scores generated an AUROC of 0.91 (95% CI 0.88-0.93) compared with 0.89 (95% CI 0.86-92) for a model using unweighted scores (chi-square P value<.001). Setting a diagnostic cut-point to optimize sensitivity at 90%, 77.5% (465/600) were graded correctly, with 90.3% sensitivity, 68.5% specificity, and an AUROC of 0.79 (95% CI 0.76-0.83). Crowdsourced interpretations of retinal images provide rapid and accurate results as compared with a gold-standard grading. Creating a logistic regression model using Rasch analysis to weight crowdsourced classifications by worker ability improves accuracy of aggregated grades as compared with simple majority vote.


What is the chance that a patella dislocation will happen a second time: update on the natural history of a first time patella dislocation in the adolescent.
Patellar instability occurs mainly in young patients and shows a high incidence of concomitant cartilage injuries. Recently there has been a strong attempt to identify risk factors and enhance imaging techniques to detect patients with an increased risk for recurrent patella dislocation.We describe current findings on factors associated with recurrent patella dislocation in the adolescent. Trochlear dysplasia, patellar height, patellar tilt, tibial tuberosity-trochlear groove distance, skeletal maturity, and history of contralateral patellar dislocation are well known significant risk factors for recurrence in adolescent patients. Predictive models to calculate risk of recurrence have been reported recently. The Patellar Instability Severity Score was the first to include demographic and anatomic factors, which is of major value when counseling patients and relatives. Several classification systems to predict the rate of recurrence after primary patella dislocation have been presented over the last years. Anatomic risk factors such as skeletal immaturity, trochlear morphology, patellar height, patellar tilt, and elevated tibial tuberosity-trochlear groove distance have been investigated. However, there is still a lack of knowledge as to how single risk factors or their interaction with each other may contribute.


Isolation and Characterization of Actinobacteria from Algerian Sahara Soils with Antimicrobial Activities.
Extreme ecosystems can be a source of untapped microorganisms to produce novel bioactive compounds of industrial interest. Consequently, in this work, 32 actinomycetes were isolated from 6 soil samples collected from Algerian Sahara in searching for untapped producers of novel antimicrobial compounds. All the isolates were further subjected to antimicrobial screening against pathogenic bacteria, yeast and fungi. The obtained results indicated that three of the isolates (named C, MS1 and 10) showed antimicrobial activities against most of the tested pathogenic microorganisms. Therefore, these three promising isolates, previously identified as Streptomyces by morphological, biochemical and physiological methods, were selected for their subsequent identification by the whole cell matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. Thus, the isolates C, MS1 and 10 were identified as Streptomyces violaceoruber B263 UFL, Streptomyces albus B262 UFL and Streptomyces badius B192 UFL, respectively. These results pointed out actinomycetes from Sahara soils as potential sources of novel antimicrobial compounds. Also, MALDI-TOF MS showed to be a robust technique for bacteria identification.


Genomics for paediatricians: promises and pitfalls.
In recent years, there have been significant advances in genetic technologies, evolving the field of genomics from genetics. This has huge diagnostic potential, as genomic testing increasingly becomes part of mainstream medicine. However, there are numerous potential pitfalls in the interpretation of genomic data. It is therefore essential that we educate clinicians more widely about the appropriate interpretation and utilisation of genomic testing.


The frenulum labii inferioris laterale.
A lateral counterpart to the frenulum of the lower lip, located between the dens caninus and the area of the angle of the mouth is reviewed. Anatomical considerations are discussed and the term frenulum labii inferioris laterale is suggested.


Tuberculosis patients and practitioners in private clinics in India.
Rural and urban areas of Maharashtra, a large state in Western India. To understand tuberculosis (TB) management practices among private medical practitioners (PPs) and the treatment behaviour of the patients they manage. Prospective study of help-seeking patterns and treatment behaviour among 173 pulmonary TB patients diagnosed in private clinics, and the TB management practices of 122 PPs treating these patients. The first source of help for 86% of patients was a PP. The diagnostic and treatment practices of PPs were inadequate; 15% did not consider sputum examination to be necessary, and 79 different treatment regimens were prescribed by 105 reporting PPs. Sixty-seven percent of the patients diagnosed in private clinics remained with the private sector, and the rest shifted to public health services within six months of treatment. The treatment adherence rate among the patients in private clinics was 59%. There were discrepancies between the reported management practices of the PPs and what their patients actually followed. The study identifies and highlights the need to educate PPs and their TB patients, and indicates ways in which PPs could be meaningfully involved in efforts to revitalize the national TB control programme.


Feigning Amnesia Moderately Impairs Memory for a Mock Crime Video.
Previous studies showed that feigning amnesia for a crime impairs actual memory for the target event. Lack of rehearsal has been proposed as an explanation for this memory-undermining effect of feigning. The aim of the present study was to replicate and extend previous research adopting a mock crime video instead of a narrative story. We showed participants a video of a violent crime. Next, they were requested to imagine that they had committed this offense and to either feign amnesia or confess the crime. A third condition was included: Participants in the delayed test-only control condition did not receive any instruction. On subsequent recall tests, participants in all three conditions were instructed to report as much information as possible about the offense. On the free recall test, feigning amnesia impaired memory for the video clip, but participants who were asked to feign crime-related amnesia outperformed controls. However, no differences between simulators and confessors were found on both correct cued recollection or on distortion and commission rates. We also explored whether inner speech might modulate memory for the crime. Inner speech traits were not found to be related to the simulating amnesia effect. Theoretical and practical implications of our results are discussed.


Harnessing the lymph node microenvironment.
To evaluate role of the lymph node in immune regulation and tolerance in transplantation and recent advances in the delivery of antigen and immune modulatory signals to the lymph node. Lymph nodes are a primary site of immune cell priming, activation, and modulation, and changes within the lymph node microenvironment have the potential to induce specific regulation, suppression, and potentially tolerance. Antigen enters the lymph node either from tissues via lymphatics, from blood via high endothelial venules, or directly via injection. Here we review different techniques and materials to deliver antigen to the lymph node including microparticles or nanoparticles, ex-vivo antigen presenting cell manipulation, and use of receptor conjugation for specific intralymph node targeting locations. The promising results point to powerful techniques to harness the lymph node microenvironment and direct systemic immune regulation. The materials, techniques, and approaches suggest that translational and clinical trials in nonhuman primate and patients may soon be possible.


Risk Factors for Short-term Complications After Rotator Cuff Repair in the United States.
To use a population-level dataset to evaluate the rate of 30-day complications after rotator cuff repair, and to evaluate the risk factors for complication and unplanned hospital readmission. We used the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2015 to identify patients who underwent rotator cuff repair and concomitant procedures using Current Procedural Terminology codes. Postoperative complications and unplanned hospital readmissions were identified. Patient demographics, medical comorbidities, and perioperative variables were used in a multivariate logistic regression model to identify the risk factors for infection, any complication, and unplanned hospital readmission. A total of 23,741 patients were identified who underwent rotator cuff repair. Overall, 1.39% of patients experienced at least 1 complication, with 0.66% minor complications and 0.85% major complications. Unplanned readmission occurred in 1.16% of patients. Infection was the most common complication, occurring in 0.3% of patients (n = 72), and was the most common reason for return to the operating room. Open rotator cuff repair and male gender were independent risk factors for all outcomes. Increased age and numerous medical comorbidities were associated with the risk of any complication or unplanned hospital readmission. Rotator cuff repair has a low incidence of short-term complications. Infection was the most common complication. Open repair, male gender, increased age, and medical comorbidities all significantly increased the risk of complications and hospital readmission. Level IV, case series.


Donor heart and lung procurement: A consensus statement.
Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.


Effects of dantrolene on ischemia-reperfusion injury in animal models: a review of outcomes in heart, brain, liver, and kidney.
Ischemia-reperfusion (IR) is the restoration of blood flow to a tissue that was formerly deficient of blood flow. Tissue damage after IR is considered an IR injury (IRI). During IR, there is an increased level of cytosolic calcium ([Ca(2+)]i) due to the release of calcium from mitochondrial, sarcoendoplasmic reticulum, and nuclear organelles. Dantrolene sodium (dantrolene) is a 1-[[[5-(4-nitrophenol)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt with a nonspecific mechanism, inhibiting organelle release of Ca(2+) into the cytosol. This work reviews the outcomes of administering dantrolene in brain, heart, liver, and kidney animal models of IRI. An extensive PubMed, MEDLINE, and MEDLAR literature review during the last 30 years on the effect of dantrolene in IRI in animal models was analyzed to determine the clinical implications of this important study. Particular attention was given to dantrolene in heart, brain, liver, and kidney IRI. Heart: Nine studies of heart IRI were reviewed and include an in vivo dog model (n = 1), in vivo rabbit model (n = 1), isolated dog myocardial fibers (n = 1), and isolated rat hearts (n = 6). Four studies showed decreased infarct size and increased cardiac function after IRI. One in vivo rabbit study found no difference in infarct size or cardiac function after IRI versus controls. Dantrolene may be protective or inductive of post-IRI arrhythmias depending on preestablished myocyte cycling times. Brain: Nine studies of brain IRI were reviewed and include an in vivo dog model (n = 1), in vivo gerbil model (n = 2), and in vivo rat models (n = 6). Dantrolene shows protective decreases in apoptotic markers in 6 studies, but it shows no effect on the necrotic core and mixed effects on reduction of infarct volume. One study found increased mortality in the dantrolene group. Liver: One study of in vivo rat liver IRI found that dantrolene decreased liver function tests, tissue necrosis factor α, tissue necrosis, and increased interleukin 10. Kidney: One study of in vivo rat kidney IRI showed that dantrolene had no effect. Dantrolene shows protective effects in animal models of heart, brain, and potentially liver IRI, reinforcing the importance of calcium homeostasis during IRI. Variations of dose, timing of administration, route of administration, and outcomes between studies make definitive conclusions difficult. The nonspecific mechanism of action of dantrolene may also account for the variation among studies. Lack of studies in the liver and kidney makes any consensus in these organs premature, and thus, emphasis for this review was put on studies of the heart and brain.


[Complex automatic data processing in multi-profile hospitals].
The computerization of data processing in multi-disciplinary hospitals is the key factor in raising the quality of medical care provided to the population, intensifying the work of the personnel, improving the curative and diagnostic process and the use of resources. Even a small experience in complex computerization at the Botkin Hospital indicates that due to the use of the automated system the quality of data processing in being improved, a high level of patients' examination is being provided, a speedy training of young specialists is being achieved, conditions are being created for continuing education of physicians through the analysis of their own activity. At big hospitals a complex solution of administrative and curative diagnostic tasks on the basis of general hospital network of display connection and general hospital data bank is the most prospective form of computerization.


Trends and predictors of length of stay after primary percutaneous coronary intervention: a report from the CathPCI registry.
Post hoc analyses of clinical trials suggest that certain patients are eligible for early discharge after ST-segment elevation myocardial infarction. The extent to which ST-segment elevation myocardial infarction patients are discharged early after primary percutaneous coronary intervention (PPCI) in current practice is unknown. We examined 115,113 patients in the CathPCI Registry to assess temporal trends in length of stay (LOS) after PPCI. Baseline characteristics were compared between patients with LOS ≤2 and >2 days. Predictors of LOS >2 days were determined by logistic regression and adjusted for clustering among centers. Patterns of discharge within 2 days for low-risk patients with no inhospital complications were examined. From January 2005 through March 2009, mean LOS (4.0 ± 3.0 to 3.6 ± 2.7 days) (P for trend <.001) and the proportion of patients discharged after 2 days decreased (72.0%-65.9%), while predicted inhospital mortality risk remained unchanged. Patients with LOS >2 days (n = 77,471; 67.3%) were older and more likely to have had an intra-aortic balloon pump, cardiogenic shock, transfusions, and post-PPCI complications. Of 958 hospitals, 437 (45.6%) discharged at least half of their low-risk patients with no inhospital complications within 2 days. While the predicted risk profile has remained stable, there has been a significant decrease in LOS after PPCI. Nevertheless, hospitals vary in discharging low-risk and uncomplicated patients early. Discharge within 2 days was associated with specific patient, procedure, and hospital factors. Further study is needed to determine the safety of early discharge among patients undergoing PPCI.


Molecular and biological characterization of a non-glycosylated isolate of St Louis encephalitis virus.
The glycosylation patterns of the envelope (E) glycoprotein of several naturally occurring strains of St Louis encephalitis (SLE) virus were investigated. SLE viruses were found that contained both glycosylated and non-glycosylated E proteins, and one isolate (Tr 9464) that lacks N-linked glycosylation sites on its E protein was identified. SLE virus monoclonal antibodies that define E protein B cell epitopes and demonstrate biological activities reacted essentially to the same extent with glycosylated and non-glycosylated virions. These results indicate that glycosylation is not essential for epitope conformation or recognition. However, failure to glycosylate the E protein was associated with possible morphogenetic differences as manifested by reduced virus yields and differences in specific infectivity.


Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration.
uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility.


Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products.
A cultivation-dependent approach revealed that highly diverse populations of Streptomyces were present in atmospheric precipitations from a hailstorm event sampled in February 2016 in the Cantabrian Sea coast, North of Spain. A total of 29 bioactive Streptomyces strains isolated from small samples of hailstone and rainwater, collected from this hailstorm event, were studied here. Taxonomic identification by 16S rRNA sequencing revealed more than 20 different Streptomyces species, with their closest homologs displaying mainly oceanic but also terrestrial origins. Backward trajectory analysis revealed that the air-mass sources of the hailstorm event, with North Western winds, were originated in the Arctic Ocean (West Greenland and North Iceland) and Canada (Labrador), depending on the altitude. After traveling across the North Atlantic Ocean during 4 days the air mass reached Europe and precipitated as hailstone and rain water at the sampling place in Spain. The finding of Streptomyces species able to survive and disperse through the atmosphere increases our knowledge of the biogeography of genus Streptomyces on Earth, and reinforces our previous dispersion model, suggesting a generalized feature for the genus which could have been essential in his evolution. This unique atmospheric-derived Streptomyces collection was screened for production of bioactive secondary metabolites. Analyses of isolates ethyl acetate extracts by LC-UV-MS and further database comparison revealed an extraordinary diversity of bioactive natural products. One hundred molecules were identified, mostly displaying contrasted antibiotic and antitumor/cytotoxic activities, but also antiparasitic, antiviral, anti-inflammatory, neuroprotector, and insecticide properties. More interestingly, 38 molecules not identified in natural products databases might represent new natural products. Our results revealed for the first time an extraordinary diversity of Streptomyces species in the atmosphere able to produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products.