Nitric oxide as a local mediator of prostaglandin F2alpha-induced regression in bovine corpus luteum: an in vivo study.
To test whether nitric oxide (NO) is involved in prostaglandin (PG) F2alpha-induced regression of the bovine corpus luteum (CL) in vivo, heifers were treated as follows: Group 1, saline (3 ml/h); Group 2, dinoprost, an analogue of prostaglandin F2alpha (aPGF2alpha; 5 mg/0.5 h); Group III, Nomega-nitro-L-arginine methyl ester (L-NAME; 200 mg/4 h), an inhibitor of nitric oxide synthase; and Group IV, L-NAME (400 mg/4 h) and aPGF2alpha (5 mg/0.5 h). All treatments were administered by an intraluteal microdialysis system (MDS) on day 15 of the cycle. Perfusate and jugular plasma samples were collected at half-hour intervals; additionally, jugular plasma samples were collected once daily from day 16 to day 21 of the cycle. In the perfusate samples, aPGF2alpha increased P4 (P < 0.05), PGE2 (P < 0.001), and LTC4 (P < 0.05) concentrations; L-NAME increased P4 (P < 0.05) but did not change PGE2 and LTC4 (P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF2alpha caused a further increase of P4 concentration (P < 0.05) induced by L-NAME or aPGF2alpha treatment and increased PGE2 and LTC4 (P < 0.001) concentrations to the level observed after aPGF2alpha treatment. Perfusion of CL with aPGF2alpha caused luteal regression within 24 h, while perfusion with L-NAME prolonged the life span of CL to day 21 (P < 0.05). Concomitant L-NAME and aPGF2alpha treatment partially counteracted (P < 0.05) the luteal regression caused by aPGF2alpha administration. These results show that NO is involved in the process of luteolysis in the bovine CL and suggest that the luteolytic effect of aPGF2alpha may be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade.


The Effect of Dietary Intervention With High-Oleocanthal and Oleacein Olive Oil in Patients With Early-Stage Chronic Lymphocytic Leukemia: A Pilot Randomized Trial.
Oleocanthal and oleacein (OC/OL) have important in vitro and in vivo antitumor properties; however, there is no data about their anticancer activity in humans. The aim of this pilot study was to test if patients at early stage of chronic lymphocytic leukemia (CLL) could adhere to and tolerate an intervention with high OC/OL extra virgin olive oil (EVOO) and if this intervention could lead to any changes in markers related to the disease. A pilot dietary intervention (DI) was made in patients with CLL in Rai stages 0-II who did not follow any treatment (NCT04215367). In the first intervention (DI1), 20 CLL patients were included in a blind randomized study and were separated into two groups. One group (A) of 10 patients consumed 40 ml/day of high OC/OL-EVOO (416 mg/Kg OC and 284 mg/kg OL) for 3 months. A second group (B) of 10 patients consumed 40 ml/day of low OC/OL (82 mg/kg OC and 33 mg/kg OL) for 3 months. After a washout period of 9-12 months, a second intervention (DI2) only with High OC/OL-EVOO for 6 months was performed with 22 randomly selected patients (16 from the DI1 (8 from each group) and 6 new). Hematological, biochemical, and apoptotic markers were analyzed in the serum of the patients. In addition, cellular proliferation and apoptosis markers were studied in isolated proteins from peripheral blood mononuclear cells. The results of the DI1 showed beneficial effects on hematological and apoptotic markers only with High OC/OL-EVOO. During the DI2, a decrease in the white blood cell and lymphocyte count was observed (p ≤0.05), comparing 3 months before the intervention and 6 months after it. After 3 and 6 months of DI2, an increase (p ≤0.05) was observed in the apoptotic markers ccK18 and Apo1-Fas, and also in the cell cycle negative regulator p21, and also a decrease in the antiapoptotic protein Survivin, and in the cellular proliferation marker Cyclin D. This is the first clinical trial with High OC/OL-EVOO that indicates that it could be a promising dietary feature for the improvement of CLL inducing the apoptosis of their cancer cells and improving the metabolism of the patients. https://clinicaltrials.gov/ct2/show/NCT04215367, identifier: NCT04215367.


Effect of counterion valence on the pH responsiveness of polyamidoamine dendrimer structure.
An accurate determination of the structure characteristics of protonated generation 5 polyamidoamine dendrimers in aqueous solution has been conducted by analyzing the small angle neutron scattering databased on a statistical mechanics model. In our investigation, the primary focus is to elucidate the effect of counterion valence on the counterion association and its impact on the intramolecular density profile within a dendrimer. In the range of our study for molecular protonation, a strong dependence of the structural properties of charged dendrimers on counterion valence is revealed. Our findings indicate that the association of a large amount of divalent counterions significantly reduces the effective charge of a dendrimer molecule. Surprisingly, no discernible transition of the density distribution profile is observed for the dendrimer charged by D(2)SO(4), as opposed to our previous observation of a pronounced transition in intramolecular density profile for the dendrimer charged by DCl. These findings may be understood from the thermodynamic processes of counterions.


[Nursing minimum data sets (NMDS) - a literature review relating to objective and data elements].
In order to be able to follow the predicted changes in healthcare systems, there has long been a need for a unified database that could transparently compare nursing care data from different service providers. In Austria, a recommendation has been lacking thus far as to which nursing care data need to be documented as "basic data", and as a result of this, comparisons of nursing care data on a national basis have been hindered. The international development of Nursing Minimum Data Sets (NMDS) has demonstrated that nursing care data can be sufficiently compared. The aim of the systematic literature review is to raise the current level of knowledge regarding NMDS and to develop a structured description of NMDS which, above all else, can document the recorded data elements and the associated objectives with the use of NMDS. A total of seventy publications on the subject of NMDS were included in the literature overview. The analysis of the eight NMDS that were presented yielded six central objectives and six higher-level data elements. The identified objectives include: the description of the nursing care practice, distribution of the financial means, benchmarking, human resources planning, trend analyses, and quality assurance. The six data elements that were identified comprise operating data, demographic data, and the diagnoses, interventions, results (quality indicators), and intensity of nursing care (clinical data). What emerged was that no clear association is present between the objectives and the data elements of the minimum nursing care datasets that were studied.


Self-regulated methadone detoxification of heroin addicts. An improved technique in an inpatient setting.
We used a method of detoxifying heroin addicts involving a self-regulated schedule of methadone hydrochloride detoxification in an inpatient setting. This method allows the addict to receive methadone on an "as needed" basis within specified guidelines, thus permitting him to regulate his own detoxification. For this study, 30 chronic heroin addicts were detoxified using this self-regulated detoxification procedure. Measures of length of stay, amount of methadone required, and degree of patient satisfaction indicate that this is a practical means of withdrawing chronic heroin addicts that may have advantages over fixed withdrawal schedules.


Microsatellites linked to Salmonella enterica Serovar Enteritidis burden in spleen and cecal content of young F1 broiler-cross chicks.
Contamination of poultry and poultry products by Salmonella enterica Serovar Enteritidis (SE) continues to be problematic even though biosafety management practices have aided in reduction of the SE burden. Identification of molecular markers linked to disease resistance loci would further reduce SE burden by enabling selection for genetic resistance. The objectives of this study were therefore to evaluate specific genomic regions for resistance to SE burden in young broiler-cross chicks and to evaluate the interaction of allele with dam line and sex. Three hatches of F1 chicks were produced by crossing sires from a broiler breeder male line with hens from three highly inbred lines (Fayoumi 15.2, and MHC-congenic G-B1 and G-B2 Leghorn). At 1 d of age, the chicks were intraesophageally inoculated with SE phage type 13a. Spleen and cecal content samples were harvested at 1 wk, and the levels of SE were quantified by serial plate dilution. Each of the F1 chicks was genotyped with four microsatellites that had previously been shown to be linked to antibody response to SE vaccine. All four microsatellites had a significant (P < or = 0.05) main effect or interaction with dam line or sex on the level of SE in spleen and cecal contents.


Mechanism of ascorbic acid enhancement of the bioavailability and diuretic effect of furosemide.
The following possible explanations for the significant increases in the oral bioavailability and the diuretic and natriuretic effects of orally administered furosemide observed when ascorbic acid was coadministered to dogs were investigated: ascorbic acid might enhance the gastrointestinal (GI) absorption of furosemide, might inhibit GI wall metabolism of furosemide, might enhance the reabsorption of furosemide from the renal tubules, and might increase the unionized fraction of furosemide at the receptor sites. The significant increase in the oral bioavailability with coadministration of ascorbic acid seemed to result from reduced gastric first-pass metabolism of furosemide and not enhanced GI absorption of furosemide. This might be supported by rat studies; the percentages of the oral doses of furosemide recovered from the GI tract at 8 hr after oral administration were similar (p < 0.583) without (39.5%) and with (44.7%) coadministration of ascorbic acid, and the amounts of furosemide remaining per gram of stomach after 30-min incubations of 50 micrograms of furosemide with 9000g supernatant fractions of stomach homogenates were increased significantly (48.5 vs. 42.4 micrograms) by the addition of 100 micrograms of ascorbic acid. The significant increases in the diuretic and natriuretic effects of furosemide with ascorbic acid could be the result of increases in the reabsorption of furosemide from renal tubules and increases in the unionized fraction of furosemide at the renal tubular receptor sites. This was supported by 1.5-4.2-fold increases in urine output and approximately 20% decreases in the time-averaged renal clearance of furosemide when the urine pH was decreased by 1.5-2.5 units by oral administration of ammonium chloride.


Iridium-Catalyzed Intramolecular Asymmetric Allylic Etherification of Pyrimidinemethanols: Enantioselective Construction of Multifunctionalized Pyrimidine-Fused Oxazepines.
An iridium-catalyzed intramolecular asymmetric allylic etherification of pyrimidinemethanols is described. In the presence of chiral-bridged biphenyl phosphoramidite ligand L3 and triethylborane, this process provided a class of novel pyrimidine-fused oxazepanes in up to 99% yield with 99.5% enantiomeric excess. The work addresses the challenge of insufficient nucleophilicity of aliphatic alcohols for allyl substitution and indicates the vital value of chiral-bridged biphenyl phosphoramidites. Various multifunctionalized transformations of the products further demonstrate the robust synthetic utility of this methodology.


Excited states of Ru(II) and Re(I) bipyridyl complexes attached to cyclotriphosphazenes: a synthetic, spectroscopic, and computational study.
A series of new cyclotriphosphazene ligands substituted with pendant 2,2'-bipyridyl moieties, namely, bis[(1,1'-biphenyl)-2,2'-dioxy](2,2'-bipyridyl-3,3'-dioxy)cyclotriphosphazene (L(1)), bis[(1,1'-biphenyl)-2,2'-dioxy][bis{4-(2,2'-bipyridin)-4-yl-phenyoxy}]cyclotriphosphazene (L(2)), (pentaphenoxy)[4-(2,2'-bipyridin)-4-yl-phenyoxy]cyclotriphosphazene (L(3)), and (pentaphenoxy) [4-{6-phenyl(2,2'-bipyridin)-4-yl}-phenoxy]cyclotriphosphazene (L(4)), has been used to synthesize the ruthenium(II) and rhenium(I) complexes, [(L)Ru(bpy)(2)](PF(6))(4) (L = L(1) or L(3)), [(L(2)) {Ru(bpy)(2)}(2)](PF(6))(4), [(L)Re(CO)(3)Cl] (L = L(1), L(3) or L(4)), and [(L(2)) {Re(CO)(3)Cl}(2)]. Single crystal X-ray structures of [(L(1))Re(CO)(3)Cl] and [(L(4))Re(CO)(3)Cl] show the bipyridyl component of the cyclotriphosphazene substituted ligands is bound to the Re(I) giving a distorted octahedral "N(2)C(3)Cl" coordination sphere in both cases. Density functional theory (DFT) methods were employed to model the ground-state vibrational properties of the molecules, and their accuracies verified using vibrational spectroscopy. Electronic transitions were identified using UV-visible and resonance Raman spectroscopic techniques, aided by time-dependent (TD) DFT methods. Transient resonance Raman spectra of the excited states of the compounds were acquired and found to be comparable to those reported for studied metal bipyridyl units lacking the cyclotriphosphazene substituents. The cyclotriphosphazene unit has little effect on the properties of the metal bipyridyl chromophore.


Interaction between RNAs from different sources and egg lecithin liposomes.
The interaction of RNAs of molecular weight ranging between 15,000 and 30,000 with egg lecithin large and small unilamellar liposomes has been investigated. Torula and tRNA proved to be incorporated to a similar extent but no linear relationship between molecular weight and percent of incorporation was demonstrated. A relationship between percent of secondary structure of RNA and its ability to be trapped in SUV liposomes is suggested.


Adaptor Protein-3-Mediated Trafficking of TLR2 Ligands Controls Specificity of Inflammatory Responses but Not Adaptor Complex Assembly.
Innate immune engagement results in the activation of host defenses that produce microbe-specific inflammatory responses. A long-standing interest in the field of innate immunity is to understand how varied host responses are generated through the signaling of just a limited number of receptors. Recently, intracellular trafficking and compartmental partitioning have been identified as mechanisms that provide signaling specificity for receptors by regulating signaling platform assembly. We show that cytokine activation as a result of TLR2 stimulation occurs at different intracellular locations and is mediated by the phagosomal trafficking molecule adaptor protein-3 (AP-3). AP-3 is required for trafficking TLR2 purified ligands or the Lyme disease causing bacterium, Borrelia burgdorferi, to LAMP-1 lysosomal compartments. The presence of AP-3 is necessary for the activation of cytokines such as IL-6 but not TNF-α or type I IFNs, suggesting induction of these cytokines occurs from a different compartment. Lack of AP-3 does not interfere with the recruitment of TLR signaling adaptors TRAM and MyD88 to the phagosome, indicating that the TLR-MyD88 signaling complex is assembled at a prelysosomal stage and that IL-6 activation depends on proper localization of signaling molecules downstream of MyD88. Finally, infection of AP-3-deficient mice with B. burgdorferi resulted in altered joint inflammation during murine Lyme arthritis. Our studies further elucidate the effects of phagosomal trafficking on tailoring immune responses in vitro and in vivo.


Right hemisphere restitution of language and memory functions in right hemisphere language-dominant patients with left temporal lobe epilepsy.
Concomitant with the right hemispheric restitution of language functions after early left hemisphere lesions, suppression effects on originally right hemispheric visuospatial/constructional functions have repeatedly been reported. The present study evaluated this issue in 10 right hemisphere language-dominant patients with temporal lobe epilepsy. Left hemisphere language-dominant patients with left (n = 10) or right (n = 10) temporal lobe epilepsy served as controls. The following results were obtained: in all but one of the right dominant patients, left hemisphere lesions, left hemisphere foci and histories of early left brain damage indicated that secondary language transfer rather than a genetically determination is the more likely cause of the right hemisphere dominance. Despite this transfer, the language functions (comprehension, fluency, reasoning) of the right dominant patients remained significantly impaired. Language generally appeared to be better preserved in patients with an onset of epilepsy before the third year of life or a circumscribed left hemisphere lesion. No suppression effects could be detected on the level of complex cortical language and non-language functions. In contrast, on the level of temporo-limbic memory functions, verbal learning and recognition were left largely intact, albeit mostly at the expense of visuo-spatial learning and memory. The findings of the study thus indicate that the cerebral plasticity of the right hemisphere differs according to the extent of the left-hemisphere lesion, the onset of structural/functional damage and the complexity of the functions requiring restitution. Assuming that language and memory represent neocortical and palaeocortical functions, respectively, the restitution process is seemingly governed by their status in a phylogenetically determined hierarchy of functional importance.


Episiotomy and perineal trauma during childbirth.
A study was conducted to assess the frequency of episiotomy and spontaneous tears in 807 primiparas during singleton births. The incidence of episiotomy was 50%, spontaneous tears 22% and intact perineum 28%. A significantly lower frequency of episiotomy (P less than 0.001) as well as epidural anaesthesia (P less than 0.001) was found among immigrant women. There were no indications registered for 58% of the episiotomies. The non-episiotomy group experienced more clitoris/labia tears (P less than 0.01). On the other hand there was a tendency towards an increased risk for second and third degree tears, 4.2% in the episiotomy group compared to 1.7% in the non-episiotomy group (P = 0.06). Haemorrhage (greater than 600 ml) was more frequent in the episiotomy group than in the non-episiotomy group (P less than 0.001). We conclude that there is little support for the claim that episiotomy prevents tears in normal deliveries, and that the rationale for the practice of episiotomy is in need of reappraisal.


New insights into the diversity of cryptobenthic Cirripectes blennies in the Mascarene Archipelago sampled using Autonomous Reef Monitoring Structures (ARMS).
Autonomous Reef Monitoring Structures (ARMS) are artificial mini-reefs designed for standardized sampling of sessile and small motile cryptobenthic organisms. ARMS are also effective for collecting small cryptobenthic fishes, such as the combtooth blennies of the genus Cirripectes. Recent studies discovered several Cirripectes species endemic to islands or archipelagos, in spite of the generally broad distributions of tropical and subtropical blennies. Thus, to evaluate the diversity and distribution of Cirripectes species in the Mascarene Archipelago, a little-studied region but an important biodiversity hotspot, complete mitochondrial genomes, and nuclear rhodopsin genes were sequenced for 39 specimens collected with ARMS deployed on outer reef slopes at Reunion and Rodrigues islands. Mitochondrial COI sequences were analyzed to integrate these specimens within the largest dataset of publicly available sequences. Three species were found in the Mascarene Archipelago, Cirripectes castaneus, Cirripectes randalli, and Cirripectes stigmaticus. C. castaneus and C. stigmaticus both have an Indo-Pacific distribution with several haplotypes shared among distant localities. In agreement with the literature, C. randalli shows a small-range endemism restricted to the Mascarenes. We confirmed the presence of C. castaneus, C. randalli, and C. stigmaticus in Rodrigues, and the presence of C. stigmaticus in Reunion. This study contributes to filling the gaps in taxonomic and molecular knowledge of the reef cryptobiome in the South-West Indian Ocean, and provides the first complete mitogenomes for the genus, a crucial step for future molecular-based inventories (e.g., eDNA).


Tunable oscillations and chaotic dynamics in systems with localized synthesis.
Biological systems contain biochemical control networks that reside within a remarkable spatial structure. We present a theoretical study of a biological system in which two chemically coupled species, an activating species and an inhibiting species forming a negative feedback, are synthesized at unique sites and interact with each other through diffusion. The dynamical behaviors in these systems depend on the spatial locations of these synthetic sites. In a negative feedback system with two sites, we find two dynamical modes: fixed point and stable oscillations whose frequency can be tuned by varying the distance between the sites. When there are multiple synthetic sites, we find more diverse dynamics, including chaos, quasiperiodicity, and bistability. Based on this theoretical analysis, it should be possible to create in the laboratory synthetic circuits displaying these dynamics. This study illustrates the concept of "spatial switching," in which bifurcations in the dynamics occur as a function of the geometry of the system.


Gun ownership and suicide in the United States.
The circulation of firearm magazines was used as an index of gun ownership in the states of the USA. States with a higher per capita circulation of firearm magazines had higher suicide rates by gun and higher overall suicide rates. Homicide rates were unrelated to this measure of gun availability. Implications for the prevention of suicide are discussed.


A systematic analysis of religious variables in The Journal of Family Practice, 1976-1986.
One thousand eighty-six studies were reviewed to determine the prevalence, characteristics, and quality of measures of religion or religiosity in The Journal of Family Practice for the decade ending in 1986. Religious variables occurred at a relatively low rate, even among articles with some psychosocial content. The clear preponderance of religious measures pertained to patients rather than to providers, and religious variables were generally analyzed descriptively, not inferentially. In spite of an encouraging use of some measures of religious beliefs and practices, there remained a significant focus on denominational measures of religious status. These findings suggest that the consideration of religious variables in the family medicine literature has not been commensurate with the emerging picture of the role of religious commitment in health status and mental health status. It is suggested that increased emphasis on developing an original literature of record about religious variables in family medicine will promote the empirical assessment of the beneficial, neutral, and harmful effects of religion among family medicine patients and providers.


Endemism patterns are scale dependent.
Areas of endemism are important in biogeography because they capture facets of biodiversity not represented elsewhere. However, the scales at which they are relevant to research and conservation are poorly analysed. Here, we calculate weighted endemism (WE) and phylogenetic endemism (PE) separately for all birds and amphibians across the globe. We show that scale dependence is widespread for both indices and manifests across grain sizes, spatial extents and taxonomic treatments. Variations in taxonomic opinions-whether species are treated by systematic 'lumping' or 'splitting'-can profoundly affect the allocation of WE hotspots. Global patterns of PE can provide insights into complex evolutionary processes but this congruence is lost at the continental to country extents. These findings are explained by environmental heterogeneity at coarser grains, and to a far lesser extent at finer resolutions. Regardless of scale, we find widespread deficits of protection for endemism hotspots. Our study presents a framework for assessing areas for conservation that are robust to assumptions on taxonomy, spatial grain and extent.


Activation of the arousal response and impairment of performance increase with anxiety and stressor intensity.
The purpose of this study was to determine the effect of trait anxiety and stressor intensity on arousal and motor performance during a pinch task. We examined the steadiness of a precision task in the presence and absence of an imposed stressor on subjects with moderate and low trait anxiety. Subjects with the 26 highest and 14 lowest anxiety scores were assigned to one of three groups: a control group (5 women, 5 men), a moderate-anxiety group (8 women, 8 men), or a low-anxiety group (7 women, 7 men). Subjects in the anxiety groups received electric shocks and experienced significant increases in cognitive and physiological arousal compared with baseline and control subjects, especially subjects in the moderate-anxiety group. Heart rate, systolic blood pressure, and electrodermal activity were elevated during the stressor, whereas diastolic blood pressure was unchanged. Cognitive and physiological arousal tended to increase with stressor intensity and was accompanied by changes in steadiness. Although steadiness was markedly reduced with the highest intensity of shock, the average electromyogram activity was unaffected by the stressor. These findings indicate that the increase in arousal and the impairment of steadiness increased with trait anxiety and with the intensity of the noxious stimulus.


[Study on mucosal carcinomas of the large intestine, polypectomized for the recent 5 years].
Intramucosal carcinomas of the large intestine, polypectomized from 1988 to 1992 were investigated. Out of 111 lesions of intramucosal carcinoma, 106 cases (95.5%) co-existed with adenoma. The incidence of co-existence with adenoma was 0%, 14.4%, 31.5%, 26.1%, 18.9% and 9.0% in the lesions within 4mm, 5-9mm, 10-14mm, 15-19mm, 20-29mm, and over 30mm in diameter, respectively. The incidence of gross findings in the co-existed cases of cancer and adenoma was 0.9%, 15.1%, 32.1%, and 51.9% for IIa, Is, Isp, and Ip types, respectively. Histological incidence of co-existed adenomas was 63.2%, 31.1% and 5.7% for tubular, tubulovillous and villous types. Occupation rate of cancer tissue was within half in the majority of co-existed lesions.


Evaluation of Qualitative Changes in Simulated Periodontal Ligament and Alveolar Bone Using a Noncontact Electromagnetic Vibration Device with a Laser Displacement Sensor.
Evaluating periodontal tissue condition is an important diagnostic parameter in periodontal disease. Noncontact electromagnetic vibration device (NEVD) was previously developed to monitor this condition using mechanical parameters. However, this system requires accelerometer on the target tooth. This study assessed application of laser displacement sensor (LDS) to NEVD without accelerometer using experimental tooth models. Tooth models consisted of cylindrical rod, a tissue conditioner, and polyurethane or polyurethane foam to simulate tooth, periodontal ligament, and alveolar bone, respectively. Tissue conditioner was prepared by mixing various volumes of liquid with powder. Mechanical parameters (resonant frequency, elastic modulus, and coefficient of viscosity) were assessed using NEVD with the following methods: Group A, measurement with accelerometer; Group B, measurement with LDS in the presence of accelerometer; and Group C, measurement with LDS in the absence of accelerometer. Mechanical parameters significantly decreased with increasing liquid volume. Significant differences were also observed between the polyurethane and polyurethane foam models. Meanwhile, no statistically significant differences were observed between Groups A and B; however, most mechanical parameters in Group C were significantly larger and more distinguishable than those of Groups A and B. LDS could measure mechanical parameters more accurately and clearly distinguished the different periodontal ligament and alveolar bone conditions.


The stability and dynamics of ribosomal protein L9: investigations of a molecular strut by amide proton exchange and circular dichroism.
Nuclear magnetic resonance and circular dichroism experiments were used to investigate the stability and dynamic aspects of ribosomal protein L9 from Bacillus stearothermophilus in solution. This unusually shaped protein, with its two widely spaced RNA-binding domains linked by a connecting helix, has been hypothesized to serve as a "molecular strut", most likely playing a role in ribosome assembly and/or maintaining the catalytically active conformation of ribosomal RNA. Protection factors for amide proton exchange were quantitatively measured in an extensive series of NMR experiments, providing probes of the stability and dynamics of localized regions of the protein. Results show that each of the two RNA-binding domains contains a highly stable core. The exposed central helix that connects the two domains is helical in solution, albeit not rigid, a result that is supported by amide proton protection factors, circular dichroism measurements, and carbon-13 and proton chemical shift index values. A conserved glycine and lysine-rich loop in the N-terminal domain is ordered and quite stable, a surprising result, since this loop had been presumed to be disordered in the original crystallographic analysis. Interestingly, the most dynamic parts of the protein are the regions that contain the likely RNA-binding residues in each of the two domains. The present results add further support to the notion that the L9 protein plays an architectural role within the ribosome, with the central helix serving as a molecular strut, or perhaps a spring, linking the two widely spaced RNA-binding domains.


CR6-interacting factor 1 represses the transactivation of androgen receptor by direct interaction.
CR6-interacting factor 1 (CRIF1) was previously identified as a nuclear protein that interacts with members of the Gadd45 family and plays a role as a negative regulator in cell growth. However, the nuclear function of CRIF1 remains largely unknown. In this study, we demonstrate that CRIF1 acts as a novel corepressor of the androgen receptor (AR) in prostatic cells. Transient transfection studies show that CRIF1 specifically represses AR transcriptional activation of target promoters in a dose-dependent manner. Additionally, CRIF1 is recruited with AR to the endogenous AR target promoters. In vivo and in vitro protein interaction assays reveal that CRIF1 directly interacts with AR via the activation function-1 domain of AR. Interestingly, both the N-terminal and C-terminal half-regions of CRIF1 are independently capable of interacting with and repressing the transactivation of AR. CRIF1 represses AR transactivation through competition with AR coactivators. In addition, the CRIF1-mediated inhibition of AR transactivation involves the recruitment of histone deacetylase 4. Down-regulation of CRIF1 by small interfering RNA increases the transactivation of AR and the mRNA level of the AR target gene prostate-specific antigen, whereas the overexpression of CRIF1 decreases the prostate-specific antigen mRNA level. Finally, the overexpression of CRIF1 inhibits the androgen-induced proliferation and cell cycle progression of prostate cancer cells. Taken together, these results suggest that CRIF1 acts as an AR corepressor and may play an important role in the regulation of AR-positive growth of prostate cancer.


[Clinical observation of partial pancreatectomy as part of primary cytoreductive surgery in advanced epithelial ovarian cancer].
The aim of this study is to evaluate the safety and efficacy of partial pancreatectomy as part of primary cytoreductive surgery in advanced epithelial ovarian cancer (EOC). A total of 8 patients were recruited in this study who underwent partial pancreatectomy during the primary cytoreductive surgeries for advanced EOC in Fudan University Shanghai Cancer Center from April 2009 to July 2015. Their clinicopathological characteristics, diameter of metastatic tumors, the scope of cytoreductive surgeries, residual diseases after cytoreductive surgeries, postoperative complications and survival situation were retrospective analyzed. (1) Clinicopathological characteristics: the median age of these patients was 58 years old (range: 39-63 years old) . The median value of preoperative serum CA125 was 1 688 kU/L (range: 119-5 000 kU/L) . The median diameter of metastatic tumors involved in pancreatic body or tail was 4.5 cm (range: 3-10 cm). All the tumors from the 8 patients were confirmed to be high-grade serous carcinoma. Four patients were staged as International Federation of Gynecology and Obstetrics (FIGO) Ⅳ, and the other 4 patients were staged as FIGO Ⅲc. (2) Tumor metastases and the scope of cytoreductive surgeries: all of these 8 patients had widely disseminated ovarian cancer, with involvement of upper abdominal, middle abdominal and pelvic cavity. Each patient underwent extensive intra-abdominal cytoreductive surgeries, including hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic peritonectomy, splenectomy, partial pancreatectomy. Each patient had cytoreductive surgeries of 9.6 different sites on average. Of all 8 patients who underwent partial pancreatectomy, 7 patients had pancreatic tails removed; the other 1 patient had pancreatic body and tail removed. The median volume of blood loss during surgery was 1 350 ml (range: 300-3 500 ml) , blood transfusion was performed in 7 patients with the median volume of 1 150 ml (range: 500-1 800 ml). (3) Residual diseases after cytoreductive surgeries: optimal cytoreduction was achieved in all patients, with microscopic residual disease in 3 patients, residual tumors diameter < 0.5 cm in 3 patients, and residual tumors diameter between 0.5 and 1 cm in 2 patients. (4) Postoperative complications: 4 patients suffered from complications including pancreatic leakage (2/8), intraperitoneal hemorrhage (1/8) and pancreatic pseudocyst accompanied by infection (1/8). These complications were treated successfully by conservative managements. (5) Survival situation: during the median follow-up duration of 17 months (ranged from 2 to 46 months), 5 patients were still alive until the end of follow-up, including 4 cases under treatment and 1 case survived 29 months without relapse after treatment. Three patients were respectively died in 5, 20 and 46 months after surgery. There is a higher risk of postoperative complications of pancreas resection as part of primary cytoreductive surgery in advanced epithelial ovarian cancer, but the resection of pancreatic metastases and part of the pancreas is feasible and necessary.


The K1 capsular polysaccharide of Escherichia coli.
Epidemiologic, immunologic, and genetic evidence indicate that the K1 capsular polysaccharide confers invasiveness to Escherichia coli. The capsule, an alpha-2----8-linked homopolymer of sialic acid (NeuNAc), provides the bacterium with a physical antiphagocytic barrier. Structural similarities between K1 and human tissue components suggest that immune tolerance may also be a factor in pathogenesis of K1 disease. The molecular and genetic events involved in the synthesis and export of the K1 polysaccharide were examined. The cloned K1 genes encode at least 12 proteins involved in capsule biosynthesis. These genes appear to be coordinately regulated and functionally clustered. One cluster is associated with the synthesis and activation of NeuNAc and includes the gene encoding CMP-NeuNAc synthetase. This enzyme catalyzes the activation of NeuNAc to CMP-NeuNAc. A second region, encoding five proteins, is associated with translocation of polysaccharide to the bacterial surface. The K1 polysaccharide is a poor immunogen in humans, and an understanding of the key reactions involved in K1 synthesis may help in providing an alternative to anticapsular immunity.


The effect of differentiation stage of amniotic fluid stem cells on bone regeneration.
Bone tissue engineering strategies require cells with high proliferative and osteogenic potential as well as a suitable scaffold to support the development of these as they form new bone tissue. In this study, we evaluated whether the differentiation stage of amniotic fluid stem cells (AFSC) could enhance the regeneration of critical sized femoral defects in a rat model. For this purpose, AFSC were seeded onto a starch-poly(ε-caprolactone) (SPCL) scaffold and were cultured in vitro in osteogenic culture media for different periods of time in order to obtain: i) undifferentiated cells, ii) cells committed to the osteogenic phenotype and iii) "osteoblast-like" cells. In vitro results indicate that AFSC were considered to be osteogenically committed by the end of week 2 and osteoblastic-like after week 3 in culture. Constructs composed of AFSC-SPCL scaffolds from each differentiation stage were implanted into critical sized femoral defects. The quality of new tissue formed in the defects was evaluated based on micro-CT imaging and histological analysis of constructs retrieved at 4 and 16 weeks after implantation. In vivo formation of new bone was observed under all conditions. However, the most complete repair of the defect was observed after 16 weeks in the animals receiving the SPCL scaffolds seeded with osteogenically committed AFSC. Furthermore, the presence of blood vessels was noted in the inner sections of the scaffolds suggests that these cells could potentially be used to induce bone regeneration and angiogenesis in non-union bone defects.


Important of case-reports/series, in rare diseases: Using neuroendocrine tumors as an example.
At present the publishing of case reports or case series involving small numbers of cases is controversial. While in the past they were commonly published by most journals, recently a number of prominent journals have either stopped publishing them or markedly reduced the numbers published. However, recently an increasing case is being made for their value and a number of new journals have been started devoted specifically to their publication. One of the arguments used for their value is their prominent role in rare diseases either in their recognition, full description or development of treatments. However this aspect has not been specifically studied. In this editorial this aspect is specifically examined using their role in neuroendocrine tumors as an example. Furthermore, the background of the controversy is briefly reviewed to better understand the context of this editorial.


Paediatric Intracranial Aneurysms: Long-term Angiographic and Clinical Outcomes in a Contemporary Series.
Paediatric aneurysms are rare and difficult to treat. Studies on the long-term angiographic and clinical outcomes conducted within the past decade are lacking. We aimed to investigate the clinical and radiographic outcomes of paediatric aneurysms treated with different strategies in a contemporary series. We performed a retrospective medical record review of paediatric patients examined at our institution between 2011 and 2018. Patient charts were retrospectively reviewed for age, presentation, type and location of the aneurysm, modalities of treatment, complications, and clinical and angiographic outcomes. The rates of aneurysm recurrence and de novo formation were determined. We evaluated 61 patients (mean age, 11.6 years; 23 females, 38 males) with 69 intracranial aneurysms. Their presentations included headache, neurological deficits, aneurysmal subarachnoid haemorrhage, incidental aneurysm, and traumatic subarachnoid haemorrhage. Of the aneurysms, 30 (49.2%) were giant. Forty-five (73.8%) patients underwent treatment for their aneurysms, and 16 (26.2%) patients were managed conservatively. The perioperative morbidity rate was 17.8%. There were no deaths. The long-term morbidity rate was 4.6%. The clinical outcomes were favourable in 82.2 and 95.3% at discharge and follow-up, respectively (mean, 41.5 months; range, 1.5-9 years). For treated aneurysms, 2/43 (4.6%) risk of aneurysm recurrence, 1/43 (2.3%) risk of aneurysm bleeding, 1/43 (2.3%) risk of de novo aneurysm formation. The annual bleeding, recurrence, and de novo formation or growth risk were 0.7, 1.4, and 0.7%, respectively. In neurovascular centres where microsurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. However, they have higher rates of recurrence and a greater risk of de novo formation or growth than their adult counterparts, which mandates lifelong follow-up.


Trajectories of a set of ten functional somatic symptoms from adolescence to middle age.
Functional somatic symptoms (FSS), or symptoms without a clear medical explanation are a considerable challenge for health care systems. There is no general consensus as to which symptoms should be regarded functional. Few longitudinal studies on the development of FSS exist and these have mainly been based on the assumption that the factorial structure of a FSS scores variable remains invariant over time. When the analysis covers longer periods of the life course, this may be challenged. The aim of our study was to investigate how ten functional somatic symptoms (FSS) evolve when individuals are ageing. The data of the Northern Swedish Cohort (n = 1001) from questionnaire surveys at ages 16, 18, 21, 30 and 42, were analysed. Participation rates remained very high over the five surveys. The list of symptoms included backache, breathlessness, dizziness, fatigue, headache or migraine, nausea, overstrain, palpitations, sleeplessness and stomach ache. We used multivariate trajectory analysis (TA) with logistic broken-stick regression models to describe sub-groups in the data. In multivariate TA the joint development of the set of item variables can be investigated. There is no need to construct a special FSS summary score variable. Four well separated trajectories were identified. In two groups, healing symptoms (25.4% of the sample) and low symptom load (32.2% of the sample), the symptom level stayed relatively low in adulthood. In the third group of high symptom load (17.2%) the probability of having symptoms was high for all FSS variables. In the fourth group of increasing symptoms (25.3%) the level of symptoms was first intermediate, but increased markedly with age. Instead of a single FSS score we were able to assign each individual to one of four trajectories described jointly by 10 separate symptoms. The profile of development, but not the probability level, was rather similar over the symptoms within the trajectories, with few exceptions. The results provide better understanding of the longitudinal development of the symptoms from the adolescence to the middle age.


Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.
The function of a new long non-coding RNA linc00673 remains unclear. While identified as an oncogenic player in non-small cell lung cancer (NSCLC), linc00673 was found to be anti-oncogenic in pancreatic ductal adenocarcinoma (PDAC). However whether linc00673 regulated malignancy and epithelial mesenchymal transition (EMT) has not been characterized. Cell proliferation was assessed using CCK-8 and EdU assays, and cell migration and invasion were assessed using scratch assays and transwell invasion assays. Epithelial mesenchymal transition was examined using western blot, qRT-PCR and immunofluorescence staining. Interaction between miRNA and linc00673 was determined using luciferase reporter assays. In vivo experiments were performed to assess tumor formation. In addition, the expression data of NSCLC specimens of TCGA and patient survival data were utilized to explore the prognostic significance of linc00673. In the present study, we found high linc00673 expression was associated with poor prognosis of NSCLC patients. In vitro experiments showed linc00673 knockdown reversed TGF-β induced EMT, and miR-150-5p was predicted to target linc00673 through bioinformatics tools. Overexpression of miR-150-5p suppressed lin00673's expression while inhibition of miR-150-5p led to significant upregulation of lin00673, suggesting that linc00673 could be negatively regulated by miR-150-5p, which was further confirmed by the inverse correlation between linc00673 and miR-150-5p in NSCLC patients' specimen. Furthermore, we proved that miR-150-5p could directly target linc00673 through luciferase assay, so linc00673 could sponge miR-150-5p and modulate the expression of a key EMT regulator ZEB1 indirectly. In addition, miR-150-5p inhibition abrogated linc00673 silence mediated proliferation, migration, invasion and EMT suppressing effect. Moreover, the inhibition of linc00673 significantly attenuated the tumorigenesis ability of A549 cells in vivo. We validated linc00673 as a novel oncogenic lncRNA and demonstrated the molecular mechanism by which it promotes NSCLC, which will advance our understanding of its clinical significance.


Unicellular and multicellular developmental variations in algal zygotes produce sporophytes.
The emergence of sporophytes, that is, diploid multicellular bodies in plants, facilitated plant diversification and the evolution of complexity. Although sporophytes may have evolved in an ancestral alga exhibiting a haplontic life cycle with a unicellular diploid and multicellular haploid (gametophyte) phase, the mechanism by which this novelty originated remains largely unknown. Ulotrichalean marine green algae (Ulvophyceae) are one of the few extant groups with haplontic-like life cycles. In this study, we show that zygotes of the ulotrichalean alga Monostroma angicava, which usually develop into unicellular cysts, exhibit a developmental variation producing multicellular reproductive sporophytes. Multicellular development likely occurred stochastically in individual zygotes, but its ratio responded plastically to growth conditions. Sporophytes showed identical morphological development to gametophytes, which should reflect the expression of the same genetic programme directing multicellular development. Considering that sporophytes were evolutionarily derived in Ulotrichales, this implies that sporophytes emerged by co-opting the gametophyte developmental programme to the diploid phase. This study suggests a possible mechanism of sporophyte formation in haplontic life cycles, contributing to the understanding of the evolutionary transition from unicellular to multicellular diploid body plans in green plants.


Differences in serum IL-6 response after 1 °C rise in core body temperature in individuals with spinal cord injury and cervical spinal cord injury during local heat stress.
Passive rise in core body temperature achieved by head-out hot water immersion (HHWI) results in acute increases in serum interleukin (IL)-6 but no change in plasma adrenaline in patients with cervical spinal cord injury (CSCI). The purpose of the present study was to determine the mechanism of heat stress-induced increase in serum IL-6. A cross-sectional study. The study subjects were nine with CSCI, ten with thoracic and lumbar spinal cord injury (TLSCI) and eight able-bodied (AB) subjects. Time since injury was 16.1 ± 3.4 years in TLSCI and 16.4 ± 4.1 years in CSCI. Subjects were subjected to lower-body heat stress (LBH) by wearing a hot water-perfused suit until 1 °C increase in core temperature. The levels of serum IL-6, plasma adrenaline, tumour necrosis factor (TNF)-α, C-reactive protein (CRP), and counts of blood cells were measured at normothermia and after LBH. Serum IL-6 concentrations increased significantly immediately after LBH in all the three groups. ΔIL-6% was lower in CSCI subjects compared with AB subjects. Plasma adrenaline concentrations significantly increased after LBH in AB and TLSCI subjects, but did not change throughout the study in CSCI subjects. Cardiac output and heart rate increased at the end of LBH in all three groups. Under a similar increase in core temperature, ΔIL-6% was lower in the CSCI group compared with the AB group. These findings suggest that the observed rise in IL-6 during hyperthermia is mediated, at least in part, by plasma adrenaline.


Synthesis of plasmonic nanocomposites for diverse applications.
We report the synthesis of gold and silver nanostructures embedded in different dielectric matrices by atom beam co-sputtering, a novel technique. We have synthesized gold-silicon core shell nanostructures and Au-ZnO nanocomposite with tunable surface plasmon resonance (SPR) by atom beam co-sputtering and subsequent annealing. The Au-ZnO nanocomposite shows significant enhancement in intensity of Raman modes of fullerene molecules and therefore can help in surface enhanced Raman spectroscopy investigation of organic molecules. The synthesized Ag-polymer nanocomposite thin films show excellent features of broad SPR absorption extending upto IR region and a narrow transmission of light in UV region approximately 320 nm which could be of technological interest in solar absorbers and UV light filters respectively. The Ag-silica nanocomposite thin films show their utility in glucose sensing. The gold-silica nanocomposite thin films exhibit their possible use in detection of human ovarian cancer cells in a preliminary study. The shift in SPR peak of Au nanoparticles (NPs) present at the surface of silica synthesized by thermal evaporation and annealing, after attachment of biological molecules like proteins has been studied.


Updates in periprocedural management of direct oral anticoagulants.
As the prevalence of patients on antithrombotics is increasing, anesthesiologists must have a firm understanding of these medications and considerations for their periprocedural management. This review details up-to-date periprocedural management of direct oral anticoagulants (DOACs). DOACs have favorable pharmacokinetics including quick onset of action and short half-lives. Periprocedural management of DOACs relies heavily on drug half-life as well as procedural risk of bleeding. Other than a few exceptions, the American College of Cardiologists generally recommends complete clearance of oral anticoagulants prior to high-risk bleeding procedures and partial clearance prior to low-risk bleeding procedures. Procedures with little to no clinical risk of bleeding can be performed without any drug interruption or during trough levels. Exceptions to periprocedural DOAC management pertain to electrophysiology procedures. With the exception of no clinically relevant bleeding risk or certain electrophysiology procedures, DOACs should be discontinued periprocedurally in accordance with bleeding risks and drug's half-life. Bridging is generally not recommended for DOACs.


Diagnostic performance and clinical feasibility of a point-of-care test for respiratory viral infections in primary health care.
Inappropriately high levels of antibiotics are still prescribed in primary health care for respiratory tract infections (RTIs). Access to diagnostic point-of-care tests (POCTs) for RTIs might reduce this over-prescription. The purpose of our study was to determine the diagnostic performance and clinical feasibility of a recently developed diagnostic POCT for respiratory viruses, the mariPOC®, in a Dutch primary healthcare setting. In patients with RTI symptoms presenting to a family practice during the 2015-2016 winter season, we determined the test's sensitivity and specificity relative to polymerase chain reaction (PCR) testing performed in a laboratory. The clinical feasibility of the POCT was evaluated by interviewing general practitioners (GPs). One or more respiratory viruses were detected in 54.9% of the patients (n = 204). For influenza A virus (n = 24), sensitivity of the POCT was 54.2% and specificity was 98.9%; for influenza B virus (n = 18), sensitivity was 72.2% and specificity 99.5%; and for respiratory syncytial virus (RSV) (n = 12), sensitivity was 50.0% and specificity 100%. In samples with higher viral load, sensitivity was 85.7% for influenza A, 78.6% for influenza B and 85.7% for RSV. The availability of a diagnostic test for respiratory viruses was appreciated by both patients and GPs. Our study shows that diagnostic POCTs for respiratory viruses might contribute to a precise and evidence-based diagnosis of RTIs and could positively influence prescription of antibiotics by GPs. However, before implementation in primary healthcare, diagnostic accuracy of the POCT needs improvement and it is impact on clinical decision making should be further assessed.


Regulatory role of autophagy in globular adiponectin-induced apoptosis in cancer cells.
Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.


Comparison of the effects and side-effects of sedation with propofol versus midazolam plus pethidine in patients undergoing endoscopy in Imam Khomeini Hospital, Ahvaz.
Gastrointestinal endoscopy is an invasive and diagnostic procedure that causes the patients considerable pain, discomfort, and anxiety. Therefore, various types of sedation and analgesia techniques have been used during the procedure. To compare the effects and side-effects of sedation with propofol versus midazolam plus pethidine in patients undergoing endoscopy. This is a randomised controlled double-blind clinical trial study conducted on 272 patients undergoing diagnostic and treatment endoscopy and colonoscopy in Imam Khomeini Hospital in Ahvaz between 2017 and 2018. The patients were randomly assigned to two groups. Patients in the first group (n = 136) received propofol with midazolam and ketamine, and the second group (n = 136) received pethidine and midazolam. Study outcome measures included the recovery time, patient satisfaction, quality of sedation, and adverse events. The occurrence of complications was higher in the propofol group (25% vs. 0%; p = 0.0001). No serious adverse events were observed in the study groups. Overall patient satisfaction and quality of sedation assessment scores in the propofol group were significantly better than those seen in the pethidine-midazolam group (p = 0.012 and p = 0.001, respectively). Recovery time was statistically shorter in the propofol-midazolam group (6.05 ±1.62 min) compared to the pethidine-midazolam group (6.72 ±2.21 min) (p = 0.006). Propofol-midazolam can provide better sedation, patient satisfaction, and recovery than pethidine-midazolam during endoscopy. Therefore, it can be recommended in patients scheduled for diagnostic and treatment endoscopy.


Feasibility and efficacy of combined cisplatin and irinotecan chemotherapy for poorly differentiated neuroendocrine carcinomas.
No standard treatment has been established for poorly differentiated neuroendocrine carcinoma; the usual recommended treatment is based on the strategy for small cell lung carcinoma. The aim of this study was to evaluate the response of poorly differentiated neuroendocrine carcinoma to the combination of irinotecan and cisplatin in one institution. We retrospectively reviewed 50 poorly differentiated neuroendocrine carcinoma patients treated from September 2005 to April 2011 in our institution. Patients were divided into two stages: limited disease or extensive disease. Forty-four patients received the combination chemotherapy of irinotecan and cisplatin, consisting of 4-week cycles of 60 mg/m(2) irinotecan on days 1, 8, 15 and 60 mg/m(2) cisplatin on day 1. Median age was 60 years. Median follow-up time was 11.4 months. Overall survival did not reach the median, and 1-year overall survival was 67%. The response rate was 50% (64% at first line), and progression-free survival was 4.8 months (7.3 months at first line). Grade 3-4 hematologic adverse events were seen in 29 patients (66%) and Grade 3-4 non-hematologic adverse events were seen in 20 patients (45%), but no patients died of adverse events. Multivariate analysis showed a statistically significant relationship with neuron-specific enolase elevation and poor overall survival (P= 0.016, hazard ratio 6.261, 95% confidence interval). The combination chemotherapy of irinotecan and cisplatin is moderately effective and feasible, and it should be considered as a treatment option for poorly differentiated neuroendocrine carcinoma.


Immune response characteristics in women with chlamydial genital tract infection.
Immune responses in women with chlamydial genital tract infection who achieved a bacteriologic cure were prospectively compared to those women who had an incomplete clinical response. Local anti-chlamydia IgA antibody responses were significantly diminished in the outpatient treatment group who had an incomplete response, while circulating IgG responses did not differ significantly between groups. This is in contrast to both specific and non-specific lymphoproliferative responses which were similar between uninfected controls and women with a chlamydial genital tract infection, regardless of treatment outcome. Thus, the kinetics of successful outpatient treatment of chlamydial genital tract infections may have an immunologic component which can be measured at the time of initial evaluation, and may be predictive of the clinical response to adjunctive antibiotics.


Systematic review and cost-effectiveness of pharmacokinetically guided sunitinib individualized treatment for patients with metastatic renal cell carcinoma.
Sunitinib has a narrow therapeutic window, with considerable differences between patients. Dosing based on pharmacokinetics (PK) may help overcome some of those issues. This study aims to evaluate and compare the cost-effectiveness of PK-guided individualized treatment of sunitinib with its standard dose in patients with metastatic renal cell carcinoma (mRCC). A comprehensive literature search was performed, and relevant values were used to provide information for the decision analysis model. Utility data were derived from published studies, and costs were obtained from the perspective of payers in China and the United States. A Markov model was established to evaluate the associated costs and health outcomes for patients. The primary outputs of the model included lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were conducted to evaluate the potential uncertainties of parameters. Cost-effective analysis showed that the QALY of the PK-guided group increased by 0.83 compared with that in the standard dose group. From the perspective of both countries' health systems, the cost of PK-guided dose was lower than that of standard dose. Hence, PK-guided treatment was the dominant strategy. One-way and probability sensitivity analyses confirmed the reliability of these results. On the basis of currently available data, PK-guided sunitinib treatment may be a safe, effective, and economical intervention for patients with mRCC.


Observation of a novel flow regime caused by finite electric wall conductance in an initially turbulent magnetohydrodynamic duct flow.
We present results of a series of numerical simulations of an initially fully developed turbulent flow of a liquid metal in a long duct under the influence of a constant uniform transverse magnetic field and various wall conductances (ranging from perfectly insulated to perfectly conducting walls). The changes in the wall conductance caused the appearance of novel flow regimes characterized by the coexistence of locally turbulent or laminar flow regions and a nonmonotonic behavior of the corresponding wall-friction coefficients. In contrast to the situation where an increase in the imposed magnetic field will lead to continuous suppression of turbulence and final complete relaminarization of the flow in a specific range of wall-conducting parameters, we also observe an apparent partial and complete turbulence regeneration from the magnetohydrodynamic-suppressed laminar state.


Environmental prevention in atopic eczema dermatitis syndrome (AEDS) and asthma: avoidance of indoor allergens.
Indoor allergens represent an important precipitating factor for both asthma and atopic eczema dermatitis syndromes (AEDS). There is also accumulating evidence that sensitization to those allergens is associated with the onset of atopic disorders. Patients with AEDS present aeroallergen-specific T-cell responses associated with worsening of symptoms when exposed to specific aeroallergens. Furthermore, application of indoor allergens to the skin of patient with AEDS induces a local eczematous response in one-third of these patients. Exposure to high concentrations of mite allergens in early infancy have been demonstrated to be a risk factor for developing atopic dermatitis during the first 3 years of life. Moreover, a clear dose-response relationship has been documented between mite exposure and disease activity. Primary prevention of AEDS by avoiding indoor allergen exposure has been proved to be effective only when allergenic foods have also been avoided. Mite allergen avoidance in infants with AEDS and food allergy may however, prevent mite sensitization and the onset of asthma. Indoor allergen avoidance has been demonstrated to be effective in the majority of studies performed in patients with established AEDS. Negative results may be explained either by individual susceptibility variation, by long duration of disease with the consequent irreversible pathological changes in the target tissue or by exposure to allergens outside the house. Education of the patients and public consciousness of the problems are crucial for the efficacy of indoor allergen avoidance in allergic diseases.


Could phase 3 medicine trials be tagged as pragmatic? A case study: The Salford COPD trial.
Randomized clinical trials (RCTs) can be classified as explanatory or pragmatic. Currently, explanatory and pragmatic are considered to be the extremes of a continuum: Many trials have some features of both explanatory and pragmatic RCTs. The Salford Chronic Obstructive Respiratory Disease (COPD) trial was an open-label phase 3 RCT assessing an experimental product (fluticasone furoate-vilanterol) vs usual care. The Salford investigators labelled it as "the world's first phase 3 pragmatic RCT" in COPD patients. The evaluation of the Salford trial by means of the PRECIS-2 tool, yielded a mix of both extremes (explanatory and pragmatic) with several of the 9 domains close to the explanatory extreme and few to the pragmatic one. A number of the features could not be considered as being minimal changes over usual clinical practice. Hence, it would be difficult to accept that the Salford COPD trial was a pragmatic RCT. In addition, all trial participants could have been subject to the Hawthorne effect. The scientific community needs to be rigorous enough when using certain terms related to RCT. It is clear that the Salford COPD trial had particular features-sharing some of explanatory phase 3 RCTs and some of pragmatic RCTs. This, however, is not enough to tag it as a "pragmatic" RCT providing "real-world" data. These words should not be used when referring to prelicensed RCT, unless they really describe how was the trial conducted and the type of data gathered-something that with the current clinical trial regulations will only occur in very rare circumstances.


Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins.
Citrulline malate is known to improve performance in weakened muscles. The present experiment was designed to test the hypothesis that citrulline malate can limit the effect of endotoxins on muscle fatigability. Endotoxemia was induced in rats by injection of lipopolysaccharides from Klebsiella pneumoniae. Resistance to fatigue was quantified by measuring tension production during repetitive electrical stimulation of the isolated epitrochlearis muscle. Oral treatment by citrulline malate was found to increase resistance to fatigue in infected rats, whereas twitch tension was not modified. This demonstrates the efficacy of citrulline malate for limiting an increase in muscle fatigue elicited with bacterial endotoxins.


Assessing the effect of data integration on predictive ability of cancer survival models.
Cancer is the second leading cause of death in the United States. To improve cancer prognosis and survival rates, a better understanding of multi-level contributory factors associated with cancer survival is needed. However, prior research on cancer survival has primarily focused on factors from the individual level due to limited availability of integrated datasets. In this study, we sought to examine how data integration impacts the performance of cancer survival prediction models. We linked data from four different sources and evaluated the performance of Cox proportional hazard models for breast, lung, and colorectal cancers under three common data integration scenarios. We showed that adding additional contextual-level predictors to survival models through linking multiple datasets improved model fit and performance. We also showed that different representations of the same variable or concept have differential impacts on model performance. When building statistical models for cancer outcomes, it is important to consider cross-level predictor interactions.


[Pediatric tasks related to children's health protection].
The activity of research facilities in shaping up the health of children and teenagers is elucidated. The priority trends are defined for joint research in the spheres of age-related and clinical physiology, psychology, and pediatrics as well as of hygiene of children and teenagers; as a result of such research, real methods can be suggested to monitor the health shape-up and development of children.


Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.
To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.


Exceptional Contours and Band Structure Design in Parity-Time Symmetric Photonic Crystals.
We investigate the properties of two-dimensional parity-time symmetric periodic systems whose non-Hermitian periodicity is an integer multiple of the underlying Hermitian system's periodicity. This creates a natural set of degeneracies that can undergo thresholdless PT transitions. We derive a k·p perturbation theory suited to the continuous eigenvalues of such systems in terms of the modes of the underlying Hermitian system. In photonic crystals, such thresholdless PT transitions are shown to yield significant control over the band structure of the system, and can result in all-angle supercollimation, a PT-superprism effect, and unidirectional behavior.


Conformationally constrained alpha-helical peptide models for protein ion channels.
Recently we described the design, synthesis, and characterization of some simple amphiphilic alpha-helical models for protein ion channels. These peptides, composed of only Leu and Ser residues, are hypothesized to form helical bundles capable of passing ions across phospholipid bilayers. In an effort to demonstrate that the peptides are, in fact, helical in their active ion-conducting state, the conformationally constrained amino acid, C alpha, C alpha-dimethylglycine (alpha-aminoisobutyric acid, Aib), was introduced simultaneously at three positions into one of the model peptides, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, giving H2N-(Leu-Ser-Leu-Aib-Leu-Ser-Leu)3-CONH2. Examination of a tetrameric model for the channel suggested that this substitution should have a minimal effect on conductance. CD spectroscopy of the Aib-modified and original peptide in phospholipid vesicles indicated that both were highly alpha-helical. Furthermore, the Aib-containing peptide formed proton channels nearly identical in conductance to the original peptide.


Pseudoxanthoma Elasticum Treatment with Fractional CO2 Laser.
Pseudoxanthoma elasticum (PE) is a rare genetic disease characterized by calcification and fragmentation of elastic fibers of the skin, retina, and cardiovascular system. We report a case of PE in which fractional carbon dioxide laser treatment was successfully used to achieve improvement of the cervical skin with 2-year follow-up, in a patient with Fitzpatrick skin type IV. After the fifth session, the patient presented with a local herpes infection. The postlaser reaction of the PE skin was similar to that of the normal skin, in terms of the duration of redness, pain, swelling, and duration of crusting. The overall cosmetic result was satisfactory, with improvement in skin texture, irregularity, volume, and distensibility. The herpetic infection reinforces the value of antiviral prophylaxis during laser treatment of extrafacial areas.


[Assessment of Impact of Acute Kidney Injury on Prognosis of a Hospitalized Patients With Acute Decompensated Heart Failure].
to assess prevalence of acute kidney injury (AKI) among patients with acute decompensated heart failure (ADHF) and its impact on prognosis in a hospitalized patient. a sample of patients hospitalized with signs of ADHF. Prevalence of AKI in this sample was 23.1%. There was no significant difference between patients with and without AKI by age, gender, and hemodynamic parameters. Portion of subjects with systolic blood pressure below 125 mm Hg among patients with AKI did not exceed one third. Development of AKI was associated with 3-fold elevation of risk of injury of the liver. Hospital mortality in patients with AKI was 7 times higher than in patients without AKI. These results resemble those obtained in foreign studies on AKI prevalence among patients with ADHF except hospital mortality which turned out to be twice higher. Acute liver injury highly prevalent among patients with AKI worsened their prognosis. Risk of lethal outcome in patients with ADHF and AKI was inversely related to diastolic blood pressure and directly depended on maximal concentrations of creatinine and aspartate aminotransferase. Management of patients with ADHF should include measures of correction of renal and hepatic dysfunction and as well as use of drugs improving prognosis during hospital stay and in remote period.


The Myth of Universal Sensitive Responsiveness: Comment on Mesman et al. (2017).
This article considers claims of Mesman et al. (2017) that sensitive responsiveness as defined by Ainsworth, while not uniformly expressed across cultural contexts, is universal. Evidence presented demonstrates that none of the components of sensitive responsiveness (i.e., which partner takes the lead, whose point of view is primary, and the turn-taking structure of interactions) or warmth are universal. Mesman and colleagues' proposal that sensitive responsiveness is "providing for infant needs" is critiqued. Constructs concerning caregiver quality must be embedded within a nexus of cultural logic, including caregiving practices, based on ecologically valid childrearing values and beliefs. Sensitive responsiveness, as defined by Mesman and attachment theorists, is not universal. Attachment theory and cultural or cross-cultural psychology are not built on common ground.


Thermal and electronic properties of macroscopic multi-walled carbon nanotubes blocks.
Massive carpets of well packed, vertically aligned and very long multiwall carbon nanotubes were synthesized by an efficient thermal Chemical Vapour Deposition process. Electrical properties of the material were evaluated, both in terms of "global" characteristics (bulk resistivity) and in terms of "local" properties (Scanning Tunnel Spectroscopy measurements) for as-grown and annealed at different temperatures samples. The behaviour of bulk resistivity as a function of temperature was evaluated in the range 3-300 K, with a four-probe technique. The resistivity shows a linear dependence with the square root of temperature in the investigated range. From the electrical analyses, it was found that the quality of the MWNTs was improved by the annealing process, since the resistivity decreases. Heat transport properties were evaluated by the laser flash technique in order to study thermal diffusivity. Moreover high temperature behavior of the specific heat capacity of single and multi-wall carbon nanotubes, was measured up to 800 K with a Differential Scanning Calorimeter.


Crystal growth of para-sexiphenyl on clean and oxygen reconstructed Cu(110) surfaces.
The formation of crystalline para-sexiphenyl (6P) films on Cu(110) and Cu(110)-(2 × 1)O (Cu-O) has been studied by low energy electron diffraction, X-ray absorption spectroscopy and both in situ and ex situ X-ray diffraction methods to elucidate the transition from the initial monolayers to crystalline thin films. It is found that, for Cu-O, a single and, for Cu(110), a double wetting layer is formed which then acts as a template for the subsequent 3D crystal growth. For both substrates the orientation of the long molecular axes of the 6P molecules in the first layers is conserved for the molecules in the bulk crystals growing on them. The main difference between both systems is that on Cu-O the first monolayer assembles in a form close to that of a 6P bulk plane which can be easily continued by crystallites grown upon them, while on the Cu(110) surface the 6P mono- and bi-layers differ substantially from the bulk structure. The bi-layer forms a complex periodically striped phase. Thin 6P films grow with the 6P(203) crystal plane parallel to the Cu-O substrate surface. For this orientation, the 6P molecules are stacked in layers and the molecules demonstrate only one tilt of the mean molecular plane with respect to the sample surface. On clean Cu(110), a more complex 6P(629) plane is parallel to the substrate surface and this orientation is likely a consequence of the super-molecular long-range periodicity of the second molecular layer striped phase.


The influence of age on the clinical presentation and outcome of stroke.
Of 135 patients who survived the first 2 weeks following a stroke 25% were under the age of 65 years, 40% between 65 and 74 years and 35% were 75 years of age or older. Those under 65 years had a lower incidence of a previous history of lower limb arthritis, balance problems, and limited mobility but a greater incidence of ischaemic heart disease than those 65 years and over. This younger age group had a lower mortality and were more likely to progress beyond severe degrees of disability. However, if only those who survived the first year are included, then there was no difference in outcome between the age groups. In none of the parameters studied was there any difference between those 65 to 74 years of age and those 75 years and over. It was, however, those over the age of 74 years who were more likely to require long-term institutional care. These findings suggest that, although elderly 1-year survivors had a similar level of functional recovery to younger patients, other factors, probably social, affected the eventual placement of stroke patients.


New macrocyclic diterpenes from Euphorbia connata Boiss. with cytotoxic activities on human breast cancer cell lines.
Acetone:chloroform (1:2) extract of the aerial parts of Euphorbia connata Boiss. (Euphorbiaceae) was investigated for its diterpenoids. This led to the isolation of one known and two new diterpenes, belonging to the pentahydroxy-13(17)-epoxy-8,10(18)-myrsinadiene and tetrahydroxy-5,6-epoxy-14-oxo-jatropha-11(E)-ene classes. The structures were elucidated based on (13)C and (1)H NMR as well as 2D NMR, IR and MS spectra and the cytotoxicity for compounds 1-3 were evaluated by using MTT assay against two human breast cancer cell lines. Myrsinane-type compounds - 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (1) and 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (2) - exhibited moderate inhibitory effects, with IC50 values of 24.53 ± 3.39 and 26.67 ± 1.41 μM against the MDA-MB cell line, and 37.73 ± 3.41 and 34.57 ± 2.12 μM against the MCF-7 cell line, respectively. Jatrophane-type diterpene - 5,6-epoxy-8,9,15-triacetyl-3-benzoyl-14-oxo-jatropha-11(E)-ene (3) - showed weak cytotoxicity, with IC50 values of 55.67 ± 7.09 μM against MDA-MB, and moderate cytotoxicity with IC50 values of 24.33 ± 3.21 μM against MCF-7 cell line.


Extraction of intramedullary nails by proximal stacked wire technique.
We describe the use of proximal stacked wires for the removal of an intramedullary nail in the context of difficult extraction and failed attempts by conventional methods. This percutaneous technique is particularly useful for the extraction of narrow cannulated or solid intramedullary nails after failure of removal by extraction bolt devices.


Evaluation of the effect of high-intensity interval training on macular microcirculation via swept-source optical coherence tomography angiography in young football players.
This study was conducted to evaluate the effect of high intensity interval training (HIIT) on macular microcirculation, measured by swept source optical coherence tomography angiography (ss OCTA) in young football players. Football players between 18-20 years old were included. After a detailed ophthalmological examination, physiological parameters, including height, body weight, body fat, systemic blood pressure, hematocrit values, oxygen saturation, and heart rate, were recorded. Intraocular pressure and ss OCTA parameters were measured one day before and the day after the high intensity interval training program using DRI OCT Triton (Topcon, Tokyo, Japan) between 11:00 am and 1:00 pm. Fifteen participants completed the study. All were males with a mean age of 18.1 ± 0.4 years. Systolic and diastolic blood pressure and oxygen saturation did not change significantly (P > 0.05), while hematocrit levels increased remarkably (P = 0.049) after the HIIT program. Heart rates and intraocular pressure decreased (P = 0.003, P = 0.017, respectively). There was a significant increase in the central vessel density in deep capillary plexus (before: 18.7 ± 3.8%, after: 21.1 ± 4.5%) and central vessel density in choriocapillaris (before: 54.5 ± 2.8%, after 56.9 ± 2.2%) (P = 0.02, P = 0.02, respectively), although no changes were observed in other ss OCTA or in the central macular thickness and subfoveal choroidal thickness. A 6 week, high intensity interval training program with three exercise sessions per week seems not to alter mean superficial vascular densities, deep foveal avascular zone, and superficial foveal avascular zones, central macular thickness, or subfoveal choroidal thickness, while the central deep vascular density and central choriocapillaris vascular density increased remarkably among ss OCTA parameters.


On acid-base problems in REDY dialysis.
The acid-base status of dialysate and blood during REDY dialysis has been studied. A very low pH (6,90) has been found in the venous blood. However, the predialytic acidosis of the patients is corrected, which is attributed to the acetate supply during dialysis. It is pointed out that the implications of the low venous blood pH are still inadequately investigated.


Isolation and structure elucidation of the major degradation products of cefaclor formed under aqueous acidic conditions.
The aqueous acidic degradation of the oral cephalosporin cefaclor was investigated. A number of degradation products were isolated and characterized. The degradation products can be loosely classified into three categories: thiazole derivatives, pyrazine derivatives, and simple hydrolysis or rearrangement products. Degradation pathways are proposed that involve (1) hydrolysis of the beta-lactam carbonyl with subsequent rearrangement, (2) ring contraction of the six-membered cephem nucleus to five-membered thiazole derivatives through an episulfonium ion intermediate, and (3) attack of the primary amine of the phenylglycyl side chain on the "masked aldehyde" at carbon-6 to form fluorescent substituted pyrazines.


Review: the effects of childminding: how much do we know?
The literature concerning the effects of childminding is critically reviewed, and the sources of some of the evidence which has been presented, are examined. Widespread concern about the effects of minding is noted, but it is suggested that such concern is not justified by the evidence currently to hand. It is concluded that little can be safely said to be known about this subject at the present time. A new approach to research in this area is proposed.


Dendrimers Effects on the Immune System: Insights into Toxicity and Therapeutic Utility.
Dendrimers are hyperbranched polymeric nanomaterials increasingly used in research, industrial and biomedical applications. Establishing safety profile of these particles includes an understanding of their interactions with blood components and the immune system. Herein I review the literature demonstrating how tuning dendrimer physicochemical properties influences their interaction with erythrocytes, platelets, plasma proteins, complement and coagulation systems. Dendrimer immunogenicity, adjuvanticity, allergenicity, anti-inflammatory, immunosuppressive and antibacterial properties are also discussed. Dendrimers hemato- and immune- compatibility are determined by particle size, architecture, type and density of surface functional groups. Case studies from the literature are discussed to support this conclusion. The review also highlights questions which require more thorough investigation to fill the gaps in our understanding of immunological properties of dendrimers.


Development of an EMG-Controlled Serious Game for Rehabilitation.
A majority of the seven million stroke survivors in the U.S. have hand impairments, adversely affecting performance of a variety of activities of daily living, because of the fundamental role of the hand in performing functional tasks. Disability in stroke survivors is largely attributable to damaged neuronal pathways, which result in inappropriate activation of muscles, a condition prevalent in distal upper extremity muscles following stroke. While conventional rehabilitation methods focus on the amplification of existing muscle activation, the effectiveness of therapy targeting the reorganization of pathological activation patterns is often unexplored. To encourage modulation of activation level and exploration of the activation workspace, we developed a novel platform for playing a serious game through electromyographic control. This system was evaluated by a group of neurologically intact subjects over multiple sessions held on different days. Subjects were assigned to one of two groups, training either with their non-dominant hand only (unilateral) or with both hands (bilateral). Both groups of subjects displayed improved performance in controlling the cursor with their non-dominant hand, with retention from one session to the next. The system holds promise for rehabilitation of control of muscle activation patterns.


[Drugs administered to the mother during labor and neonatal jaundice].
The authors investigated the relationship between neonatal hyperbilirubinaemia and the administering of drugs to mothers during labor and delivery in 756 A.G.A. regular pregnancy born. Findings point out a statistically significant relationship (P less than 0,05) between all drugs administered to mothers, general anesthesia included, and the presence of jaundice in newborn. Authors recommend administration of drugs to women in labor and in delivery only if strictly necessary.


Electromechanical probe and automated indentation maps are sensitive techniques in assessing early degenerated human articular cartilage.
Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (four pairs of distal femurs and four pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically, (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM), and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses, and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: Region I was macroscopically degenerated, region II was macroscopically normal but adjacent to regions I and III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:858-867, 2017.


Comprehensive analysis of transcriptome data for identifying biomarkers and therapeutic targets in head and neck squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancy worldwide. Accumulating evidences have highlighted the importance of transcriptome data during HNSCC tumorigenesis. The aim of this study was to identify significant genes as effective biomarkers for HNSCC and constructed miRNA-mRNA regulatory network for a more comprehensive understanding of the underlying molecular mechanisms. A total of four independent microarrays conducted on HNSCC samples were downloaded from the Gene Expression Omnibus (GEO) and analyzed through R software. FunRich was applied to predict potential transcription factors and targeted genes of miRNAs. Protein-protein interaction (PPI) network and miRNA-mRNA regulatory network were constructed in Cytoscape. Additionally, the database for annotation, visualization, and integrated discovery (DAVID) was utilized to perform GO and KEGG pathway enrichment analyses. Validation of gene expression levels was conducted by online databases and qPCR experiments. A total of 35 and 193 differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened out by the limma package in R. The interactive network of the overlapping DEGs presented three significant modules and ten hub genes (FN1, MMP3, SPP1, STAT1, LOX, CXCL5, CXCL11, ISG15, IFIT3, and RSAD2). Predicted target genes of DEMs were visualized in Cytoscape and six miRNA-mRNA regulatory pairs were identified. Further validation demonstrated the upregulation of SLC16A1 and COL4A1 in HNSCC. We performed an integrated and comprehensive bioinformatics analysis of miRNAs and mRNAs in HNSCC, contributing to explore the underlying regulatory mechanisms and to identify genetic biomarkers and therapeutic targets for HNSCC.


Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus.
Infections with human coronavirus EMC (HCoV-EMC) are associated with severe pneumonia. We demonstrate that HCoV-EMC resembles severe acute respiratory syndrome coronavirus (SARS-CoV) in productively infecting primary and continuous cells of the human airways and in preventing the induction of interferon regulatory factor 3 (IRF-3)-mediated antiviral alpha/beta interferon (IFN-α/β) responses. However, HCoV-EMC was markedly more sensitive to the antiviral state established by ectopic IFN. Thus, HCoV-EMC can utilize a broad range of human cell substrates and suppress IFN induction, but it does not reach the IFN resistance of SARS-CoV.


Think before you extract--a case of tooth autotransplantation.
Renewed interest in autotransplantation has resulted in additional options in the treatment for rehabilitation of missing anterior teeth. Premolar teeth have been commonly used after extensive modifications while a supernumerary tooth from the anterior region when present would be a more suitable option. This case presents such a scenario, with a successful outcome ensuring adequate restoration of function, economical viability and aesthetic satisfaction for both the patient and clinician.


Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection.
Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP.


Exercise improves cytokine profile in HIV-infected people: A randomized clinical trial.
Verify the effects of concurrent training on cytokines in people living with HIV under antiretroviral therapy (ART) treatment. This was a blinded, parallel-group, clinical trial, where 49 participants, divided in two groups, either control group or concurrent training group, took part in the intervention. The control group performed recreational activities and concurrent training group participated of 16-week, 3 times per week of heart rate guided-aerobic plus resistance training for major muscular groups. Cytokines (interleukins 4, 5, 6, 8, 10, tumor necrosis factor-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor) were measured before and after 16-week experimental period using flow cytometry. From 49 participants who took part in the intervention, 28 completed the program and had data analyzed. There was a significant interaction for IL-8, which increased for control group: 7.1±5.1 vs. 8.1±6.0 and a decrease for concurrent training: 8.0±4.4 vs. 5.4±2.3. In addition, magnitude-based inference showed a likely beneficial effect for the training group when compared to the control group for IL-8, IL-5, and IL-10. The difference perceptual: mean and [CI 90%] between delta of difference within groups was -43.1 [-64.0 to -10.0] and -6.6 [-14.7 to 2.3], respectively. Short-term exercise is able to decrease the levels of IL-5, IL-8, and IL-10 in HIV-infected people undergoing ART.


A normative inference approach for optimal sample sizes in decisions from experience.
"Decisions from experience" (DFE) refers to a body of work that emerged in research on behavioral decision making over the last decade. One of the major experimental paradigms employed to study experience-based choice is the "sampling paradigm," which serves as a model of decision making under limited knowledge about the statistical structure of the world. In this paradigm respondents are presented with two payoff distributions, which, in contrast to standard approaches in behavioral economics, are specified not in terms of explicit outcome-probability information, but by the opportunity to sample outcomes from each distribution without economic consequences. Participants are encouraged to explore the distributions until they feel confident enough to decide from which they would prefer to draw from in a final trial involving real monetary payoffs. One commonly employed measure to characterize the behavior of participants in the sampling paradigm is the sample size, that is, the number of outcome draws which participants choose to obtain from each distribution prior to terminating sampling. A natural question that arises in this context concerns the "optimal" sample size, which could be used as a normative benchmark to evaluate human sampling behavior in DFE. In this theoretical study, we relate the DFE sampling paradigm to the classical statistical decision theoretic literature and, under a probabilistic inference assumption, evaluate optimal sample sizes for DFE. In our treatment we go beyond analytically established results by showing how the classical statistical decision theoretic framework can be used to derive optimal sample sizes under arbitrary, but numerically evaluable, constraints. Finally, we critically evaluate the value of deriving optimal sample sizes under this framework as testable predictions for the experimental study of sampling behavior in DFE.


Comparative distress levels of inner-city family members of homicide victims.
This study investigated the distress levels of 150 family members of homicide victims, as well as how pre-event, peri-event, and postevent variables were related to distress. Distress levels were very high, with 26% of the sample reporting clinical distress. Because it was not possible to say if this distress resulted from the homicide itself or from the fact that people who lose family members to homicide generally have lives rooted in stressful contexts, we compared the homicide sample to two sociodemographically comparable groups of 108 other trauma victims and 119 nonvictims selected from a larger epidemiological dataset. Homicide survivors were significantly more distressed than either group, suggesting that loss of a family member to homicide has definite clinical implications. Although event-related variables were somewhat predictive of distress, pre-event and postevent variables selected for this study had greater predictive utility.


Neural networks convergence using physicochemical data.
An investigation of the neural network convergence and prediction based on three optimization algorithms, namely, Levenberg-Marquardt, conjugate gradient, and delta rule, is described. Several simulated neural networks built using the above three algorithms indicated that the Levenberg-Marquardt optimizer implemented as a back-propagation neural network converged faster than the other two algorithms and provides in most of the cases better prediction. These conclusions are based on eight physicochemical data sets, each with a significant number of compounds comparable to that usually used in the QSAR/QSPR modeling. The superiority of the Levenberg-Marquardt algorithm is revealed in terms of functional dependence of the change of the neural network weights with respect to the gradient of the error propagation as well as distribution of the weight values. The prediction of the models is assessed by the error of the validation sets not used in the training process.