Analysis of flavone C-glycosides in the leaves of Clinacanthus nutans (Burm. f.) Lindau by HPTLC and HPLC-UV/DAD.
Clinacanthus nutans (family Acanthaceae) has been used for the treatment of inflammation and herpes viral infection. Currently, there has not been any report on the qualitative and quantitative determination of the chemical markers in the leaves of C. nutans. The C-glycosidic flavones such as shaftoside, isoorientin, orientin, isovitexin, and vitexin have been found to be major flavonoids in the leaves of this plant. Therefore, we had developed a two-step method using thin-layer chromatography (TLC) and high pressure liquid chromatography (HPLC) for the rapid identification and quantification of the flavones C-glycosides in C. nutans leaves. The TLC separation of the chemical markers was achieved on silica gel 60 plate using ethyl acetate : formic acid : acetic acid : water (100 : 11 : 11 : 27 v/v/v/v) as the mobile phase. HPLC method was optimized and validated for the quantification of shaftoside, orientin, isovitexin, and vitexin and was shown to be linear in concentration range tested (0.4-200 μg/mL, r(2) ≥ 0.996), precise (RSD ≤ 4.54%), and accurate (95-105%). The concentration of shaftoside, orientin, vitexin, and isovitexin in C. nutans leave samples was 2.55-17.43, 0.00-0.86, 0.00-2.01, and 0.00-0.91 mmol/g, respectively.


The soybean GmSNAP18 gene underlies two types of resistance to soybean cyst nematode.
Two types of resistant soybean (Glycine max (L.) Merr.) sources are widely used against soybean cyst nematode (SCN, Heterodera glycines Ichinohe). These include Peking-type soybean, whose resistance requires both the rhg1-a and Rhg4 alleles, and PI 88788-type soybean, whose resistance requires only the rhg1-b allele. Multiple copy number of PI 88788-type GmSNAP18, GmAAT, and GmWI12 in one genomic segment simultaneously contribute to rhg1-b resistance. Using an integrated set of genetic and genomic approaches, we demonstrate that the rhg1-a Peking-type GmSNAP18 is sufficient for resistance to SCN in combination with Rhg4. The two SNAPs (soluble NSF attachment proteins) differ by only five amino acids. Our findings suggest that Peking-type GmSNAP18 is performing a different role in SCN resistance than PI 88788-type GmSNAP18. As such, this is an example of a pathogen resistance gene that has evolved to underlie two types of resistance, yet ensure the same function within a single plant species.


Genotoxicity of Nicotiana tabacum leaves on Helix aspersa.
Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L) leaves (control group). All of the snails received leaves (tobacco and lettuce leaves were the only food provided) and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.


Is the efficacy of antidepressants in panic disorder mediated by adverse events? A mediational analysis.
It has been hypothesised that the perception of adverse events in placebo-controlled antidepressant clinical trials may induce patients to conclude that they have been randomized to the active arm of the trial, leading to the breaking of blind. This may enhance the expectancies for improvement and the therapeutic response. The main objective of this study is to test the hypothesis that the efficacy of antidepressants in panic disorder is mediated by the perception of adverse events. The present analysis is based on a systematic review of published and unpublished randomised trials comparing antidepressants with placebo for panic disorder. The Baron and Kenny approach was applied to investigate the mediational role of adverse events in the relationship between antidepressants treatment and efficacy. Fourteen placebo-controlled antidepressants trials were included in the analysis. We found that: (a) antidepressants treatment was significantly associated with better treatment response (ß = 0.127, 95% CI 0.04 to 0.21, p = 0.003); (b) antidepressants treatment was not associated with adverse events (ß = 0.094, 95% CI -0.05 to 0.24, p = 0.221); (c) adverse events were negatively associated with treatment response (ß = 0.035, 95% CI -0.06 to -0.05, p = 0.022). Finally, after adjustment for adverse events, the relationship between antidepressants treatment and treatment response remained statistically significant (ß = 0.122, 95% CI 0.01 to 0.23, p = 0.039). These findings do not support the hypothesis that the perception of adverse events in placebo-controlled antidepressant clinical trials may lead to the breaking of blind and to an artificial inflation of the efficacy measures. Based on these results, we argue that the moderate therapeutic effect of antidepressants in individuals with panic disorder is not an artefact, therefore reflecting a genuine effect that doctors can expect to replicate under real-world conditions.


Comparison of health-related outcomes for arthritis, chronic joint symptoms, and sporadic joint symptoms: a population-based study.
To examine predictors and health outcomes for individuals reporting arthritis, chronic joint symptoms (CJS), or sporadic joint symptoms (SJS) compared to those without arthritis or joint symptoms. Data from the 2008 Canadian Community Health Survey (n = 63,134, ages ≥15 years) were used for the analyses. Respondents not reporting arthritis as a long-term chronic health condition diagnosed by a health professional were asked about joint symptoms, excluding the back and neck, over the past 12 months and whether these symptoms were present on most days in the past month (CJS) or not (SJS). Log Poisson regression was used to estimate prevalence ratios (PRs) for reporting arthritis, CJS, and SJS, and for reporting health outcomes (physical activity, pain that limits activity, activity limitation, poor/fair self-rated health, and poor/fair self-rated mental health) and health service use (visits to primary care physicians, specialists, physiotherapists, and chiropractors, and overnight hospital stays). Arthritis was reported by 16.0% of the population, CJS by 10.1%, and SJS by 11.6%. Individuals with arthritis were older than those with CJS or SJS. Women reported arthritis and CJS more often. After adjusting for age, sex, socioeconomic status, lifestyle factors, and comorbidities, PRs of all outcomes were higher for the arthritis and CJS groups than the SJS group, with no significant differences in PRs for the arthritis and CJS groups, except for pain that limits activity. CJS were reported by 10% of the adult population. Similarities in outcomes to arthritis suggest that CJS have a substantial impact in the population, and that arthritis management advice is likely needed for this group.


Three new assays for rituximab based on its immunological activity or antigenic properties: analyses of sera and plasmas of RTX-treated patients with chronic lymphocytic leukemia and other B cell lymphomas.
Rituximab (RTX) is a monoclonal antibody which targets CD20 and is approved for treatment of non-Hodgkin's lymphoma (NHL), with an approximate 50% overall response rate among NHL patients. Accurate determination of RTX concentrations in patient plasmas is important for proper dosing of patients and for correlating RTX concentrations with clinical responses. There is currently no assay available for RTX which utilizes easily obtainable commercial reagents. Therefore, we sought to develop such an assay, and in this report we describe three new assays for RTX concentration. One assay, based on flow cytometry, quantitates immunologically active RTX based on its ability to bind to CD20 on Raji cells. Two other methods, based on flow cytometry and ELISA, measure RTX based on its antigenic properties. The assays are accurate, in good agreement with one another, and can all measure RTX concentrations as low as approximately 1 microg/ml in both sera and plasmas. Use of these assays reveals that chronic lymphocytic leukemia (CLL) patients receiving RTX treatment have lower plasma RTX concentrations than patients with other B cell lymphomas at all times over the usual 4-week course of therapy. The level in CLL plasmas often declines to <1 microg/ml RTX 1 week after each RTX infusion, substantially lower than the values found in comparable non-CLL patient plasmas. RTX assay results also demonstrate that naïve CLL patient plasmas do not have levels of non-cell associated CD20 sufficient to either interfere with an in vitro assay of RTX or to block the potential therapeutic action of RTX in vivo.


[The Analysis of the Causes of Sudden Deaths Among Workers of Locomotive Crews].
to analyze causes of sudden death (SD) of workers of locomotive crews. Materials and methods. We performed the retrospective analysis of SDs of employees of Joint Stock Company ( JSC) "Russian Railways" for the period 2009-2017 (total 119 cases). Results. As a rule, the combination of risk factors of development of cardiovascular diseases was present, but the SCORE scale risk of cardiac death was average. However, in 60 % of cases at life risks were not correctly assessed. Differences were found between the deceased depending on what type of locomotive they steered. Also, a part of SD victims overworked during the last month (year). Conclusion. Further improvement of work of medical service of JSC "Russian Railways" is necessary.


Brief report: Implementing and evolving suicide prevention strategies at Taoyuan Psychiatric Center inspired by NIC Umbrella review.
This brief report discusses the implementation and evolution of suicide prevention strategies at Taoyuan Psychiatric Center in Taiwan. These strategies are inspired by the nursing interventions presented in an "Umbrella review of nursing interventions NIC for the treatment and prevention of suicidal behavior." The interventions are a part of an employee assistance program (EAP) designed to support the mental health of the nursing staff and other employees, with a particular focus on preventing and managing suicidal behaviors. The EAP involves multi-tiered primary, secondary, and tertiary prevention measures, offering different levels of psychological interventions.


Bacteriocinogenic Clo DF13 minicells of Escherichia coli synthesize a protein that accounts for immunity to bacteriocin Clo DF16: action of the immunity protein in vivo and in vitro.
The Clo DF13 plasmid-specific immunity protein is able to prevent the inhibitory effect of cloacin DF13 on in vitro protein synthesis. We have shown, by gel filtration, that direct binding of the Clo DF13 immunity protein to cloacin occurs in vitro. This cloacin DF13-immunity protein complex is rather stable, and the cloacin present in the complex is no longer able to cause inhibition of in vitro protein synthesis. The binding of immunity protein to cloacin DF13 is rather specific because the Clo DF13 immunity protein does not bind to in vitro inactive cloacin and binds very poorly to the closely related bacteriocin colicin E3. Furthermore, we present data which strongly suggest that in vitro at least a fourfold excess of immunity protein is required to ensure that every cloacin molecule is inactivated by cloacin-immunity protein complex formation. Only a fraction (an about equimolar amount) of the immunity protein molecules, however, actually binds to cloacin DF13. The existence of an immunity protein-cloacin complex in vivo was concluded from the observation that cloacin, purified by chromatography on diethyl-(2-hydroxypropyl)-aminoethyl Sephadex in the absence of urea, contains an about equimolar amount of a second protein which comigrates with immunity protein on sodium dodecyl sulfate-polyacrylamide and urea-polyacrylamide gels. In an in vitro protein-synthesizing system, this component appeared to behave identical to the Clo DF13 immunity protein. The purified immunity protein-containing cloacin was at least 80 times less active in inhibiting in vitro protein synthesis, compared to cloacin, free of immunity protein. These data imply that few, if any, cloacin DF13 molecules are present in cloacinogenic cells as active, free cloacin molecules.


Validation of PROMIS Profile-29 in adults with hemophilia in the Netherlands.
The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29 questionnaire is widely used worldwide, but it has not yet been validated in the Netherlands, nor in persons with hemophilia. To validate the Dutch-Flemish version of the PROMIS-29 Profile v2.01 in adults with hemophilia. Dutch males with hemophilia (all severities) completed questionnaires that contained sociodemographic and clinical characteristics, the PROMIS-29, RAND-36, and the Hemophilia Activities List (HAL). Structural validity of each subscale was assessed with confirmatory factor analysis (CFA). Internal consistency was calculated for each subscale with sufficient model fit in CFA. Construct validity was assessed by testing hypotheses about (1) correlations of each PROMIS-29 subscale with corresponding scales of RAND-36 and domains of HAL, and (2) mean differences in T-scores between subgroups with different hemophilia severities, self-reported joint impairment, and HIV infection status. We considered ≥75% of data in accordance with the hypotheses evidence for construct validity. In total, 770 persons with hemophilia participated in this cross-sectional study. CFA revealed sufficient structural validity for five subscales: Physical Function, Depression, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Internal consistency was high and Cronbach's alpha ranged from 0.79 for Sleep Disturbance to 0.96 for Pain Interference. Differences between clinical subgroups were in the expected direction. Construct validity was confirmed for Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Intensity. This study revealed sufficient evidence for structural validity, internal consistency, and construct validity for most PROMIS Profile-29 subscales among people with hemophilia in the Netherlands.


Automated method for simultaneous lead and strontium isotopic analysis applied to rainwater samples and airborne particulate filters (PM10).
A new automated, sensitive, and fast system for the simultaneous online isolation and preconcentration of lead and strontium by sorption on a microcolumn packed with Sr-resin using an inductively coupled plasma mass spectrometry (ICP-MS) detector was developed, hyphenating lab-on-valve (LOV) and multisyringe flow injection analysis (MSFIA). Pb and Sr are directly retained on the sorbent column and eluted with a solution of 0.05 mol L(-1) ammonium oxalate. The detection limits achieved were 0.04 ng for lead and 0.03 ng for strontium. Mass calibration curves were used since the proposed system allows the use of different sample volumes for preconcentration. Mass linear working ranges were between 0.13 and 50 ng and 0.1 and 50 ng for lead and strontium, respectively. The repeatability of the method, expressed as RSD, was 2.1% and 2.7% for Pb and Sr, respectively. Environmental samples such as rainwater and airborne particulate (PM10) filters as well as a certified reference material SLRS-4 (river water) were satisfactorily analyzed obtaining recoveries between 90 and 110% for both elements. The main features of the LOV-MSFIA-ICP-MS system proposed are the capability to renew solid phase extraction at will in a fully automated way, the remarkable stability of the column which can be reused up to 160 times, and the potential to perform isotopic analysis.


Designing in quality through design control: a manufacturer's perspective.
Quality by design is a comprehensive program that begins with understanding user needs and continues through (but does not end with) monitoring customer acceptance. Management tools and processes such as ISO 9000 standards and the Food and Drug Administration Quality System Regulations exist to guide medical device manufacturers in quality practices. The goal is to deliver products acceptable for their intended use. Quality control begins with defining attributes ranging from color to accuracy and precision. Failure mode and effects analysis and risk analysis consider both probability and severity of potential malfunctions and their effects on patients or operators. Tools used to implement design and production practices include Program Evaluation and Review Technique (PERT) charts and industry-conceived concepts, such as Six Sigma techniques. Their use varies with manufacturer, depending on product and customer needs and the manufacturer's specific quality practices. Verification confirms that input goals are met. Then, validation assures that intended clinical needs are continually satisfied by establishing adequate production specifications. Conformance is monitored to verify that stable, consistent processes are in place, and precise user instructions enable the device to satisfy its intended use. Finally, complaint tracking can help assess whether needs have been met. Modifications in service, hardware, or instructions (including quality control) might be required. Therefore, both manufacturers and users work in partnership for continual improvement. The manufacturer's knowledge of design, production, and service needs of its devices enable it to recommend appropriate quality-control protocols for clinical testing.


[Waiting time for and length of physicianc's consultation define the patient-physician interaction: results of a prospective study in 478 patients with chronic viral hepatitis].
Little is known about the physician-patient interaction in hepatitis B and C. This study by the federal competence network hepatitis analysed the physician-patient interaction using the validated FAPI questionnaire. The questionnaire also contained questions concerning demography and disease characteristics. Of the total 1500 questionnaires sent out, 478 were returned (32 %) (20 % HBV vs. 80 % HCV). The FAPI index of patients with HBV/HCV infection (3.10 +/- 0,99) was lower than that in patients with other internal medicine diseases (3.61 +/- 0.92; n = 148). Women had lower values than men (2.98 vs. 3.25; p = 0.005). Patients with active HBV infection showed higher values than those with HCV infection (3.27 vs. 2.97; p < 0.05). Patients with successfully treated hepatitis B/C had higher values than those with active disease (3.36 vs. 3.02; p = 0.004). The index was lower in patients who waited > 2 weeks for the consultation when compared to those with a shorter wait (2.92 vs. 3.31; p < 0.001) and was also lower in patients who waited > 30 min at the consultation day when compared to those with a shorter wait (2.81 vs. 3.39; p < 0.001). The index gradually increased with the consultation length (2.47 < 10 min vs. 2.79 10 - 15 min vs. 3.21 15 - 30 min vs. 3.82 > 30 min; p < 0.001). The index was higher in patients seen by gastroenterologists (3.43) when compared with general practioners (3.10), internists (3.02) and clinical settings (3.13) (p < 0.05). A good information status was associated with higher FAPI values when compared with a bad information status (3.43 vs. 2.76; p < 0.001). Fibrosis, health insurance and age were not associated with FAPI index (p > 0.2). By multivariate analysis a long consultation, a good information status, patients' patience, short waiting times, and providing contact to a patient support group were independently associated with a high index. The physician-patient interaction in chronic viral hepatitis is worse than in other internal medicine diseases with problems being more pronounced in HCV infection and women when compared to men and HBV infection. Short waiting times and patients' patience ameliorated the interaction as well as the consultation length, the information status of the patient and providing contact to a patient support group. Type of health insurance did not affect either waiting times or physician-patient interaction; thus there is no hint for a two-class medicine in this part of hepatology.


Emerging Techniques in Degenerative Thoracolumbar Surgery.
There continue to be incremental advances in thoracolumbar spine surgery techniques in attempts to achieve more predictable outcomes, minimize risk of complications, speed recovery, and minimize the costs of these interventions. This paper reviews recent literature with regard to emerging techniques of interest in the surgical treatment of lumbar spinal stenosis, fusion fixation and graft material, degenerative lumbar spondylolisthesis, and thoracolumbar deformity and sacroiliac joint degeneration. There continue to be advances in minimal access options in these areas, although robust outcome data are heterogeneous in its support. The evidence in support of sacroiliac fusion appears to be growing more robust in the properly selected patient.


Dynamic Weakening by Acoustic Fluidization during Stick-Slip Motion.
The unexpected weakness of some faults has been attributed to the emergence of acoustic waves that promote failure by reducing the confining pressure through a mechanism known as acoustic fluidization, also proposed to explain earthquake remote triggering. Here we validate this mechanism via the numerical investigation of a granular fault model system. We find that the stick-slip dynamics is affected only by perturbations applied at a characteristic frequency corresponding to oscillations normal to the fault, leading to gradual dynamical weakening as failure is approaching. Acoustic waves at the same frequency spontaneously emerge at the onset of failure in the absence of perturbations, supporting the relevance of acoustic fluidization in earthquake triggering.


Influences of secondary disturbances on lodgepole pine stand development in Rocky Mountain National Park.
Although high-severity fire is the primary type of disturbance shaping the structure of lodgepole pine (Pinus contorta) stands in the southern Rocky Mountains, many post-fire stands are also affected by blowdown, low-severity surface fires, and/or outbreaks of mountain pine beetle (MPB; Dendroctonus ponderosae). The ecological effects of these secondary disturbances are poorly understood but are potentially important in the context of managing for ecological restoration and fire hazard mitigation. We investigated the effects of blowdown, surface fires, and MPB outbreaks on demographic processes in post-fire lodgepole pine stands in Rocky Mountain National Park, Colorado, USA. We used dendroecological methods to reconstruct stand characteristics prior to and following secondary disturbances for paired stands with and without secondary disturbances. Surface fire events do not kill canopy trees or trigger pulses of recruitment and as such do not have detectable influences on stand development. In contrast, both MPB and blowdown kill canopy trees and trigger pulses of tree regeneration of lodgepole pine and subalpine fir (Abies lasiocarpa). The amount and species composition of post-disturbance regeneration is dependent on the severity of the disturbance and on the time since stand initiation. Secondary disturbances of higher severity (i.e., killing >50% of the canopy trees) that occur in younger post-fire stands favor new establishment of lodgepole pine. In contrast, secondary disturbances of lower severity in older stands (>250 years) trigger a pulse of establishment of subalpine fir. The results of this study demonstrate that the high tree densities characteristic of lodgepole pine stands in the southern Rockies (southern Wyoming to northern New Mexico) are the result of dense regeneration following stand-replacing fires and that surface fires had little or no thinning effect on tree densities. Thus, current high stand densities in the study area are not the result of suppression of surface fires. Moreover, the strong pulses of regeneration following forest thinning by MPB and blowdowns imply that, depending on the degree of thinning, thinning prescriptions to reduce fuels in the lodgepole pine forest type may have the unintended consequence of increasing ladder fuels 15-20 years following treatments.


Disorders of mitochondria and related metabolism.
Mitochondrial disorders are caused by mutations in either nuclear or mitochondrial genes involved in the synthesis of respiratory chain subunits or in their post-translational control. Molecular lesions of mitochondrial DNA are a frequent cause of defective oxidative phosphorylation. Although only one mutation of nuclear-encoded oxidative phosphorylation subunits has so far been reported in humans, numerous biochemically defined disorders are attributed to nuclear gene defects. The pathogenesis of these disorders has been investigated through a combination of different expertises, including keen clinical observation, classical biochemistry and muscle morphology, molecular and cellular biology, linkage analysis and population genetic studies.


Acyl CoA:cholesterol acyltransferase genes and knockout mice.
Acyl coenzyme A:cholesterol acyltransferase (ACAT) (EC 22.214.171.124) is an enzyme, located in the endoplasmic reticulum of many types of cells, that catalyzes cholesterol ester formation from cholesterol and fatty acyl CoA substrates. Sterol esterification by ACAT or homologous enzymes is conserved in evolution dating back to yeast. The recent cloning of a human cDNA for ACAT, together with genome sequencing projects, has led to the identification of an ACAT gene family and provided molecular tools for determining ACAT's functions in vivo. Summarized here is the current knowledge concerning the molecular genetics of ACAT.


Function projective synchronization in chaotic and hyperchaotic systems through open-plus-closed-loop coupling.
Recently introduced function projective synchronization in which chaotic systems synchronize up to a scaling function has important applications in secure communications. We design coupling function for unidirectional coupling in identical and mismatched oscillators to realize function projective synchronization through open-plus-closed-loop coupling method. Numerical simulations on Lorenz system, Rossler system, hyperchaotic Lorenz, and hyperchaotic Chen system are presented to verify the effectiveness of the proposed scheme.


Prognostic Factors for Postsurgical Recovery of Deltoid Palsy due to Cervical Disc Herniations.
Retrospective multicenter study. We aimed to investigate prognostic factors affecting postsurgical recovery of deltoid palsy due to cervical disc herniation (CDH). Little information is available about prognostic factors affecting postsurgical recovery of deltoid palsy due to CDH. Sixty-one patients with CDH causing deltoid palsy (less than grade 3) were included in this study: 35 soft discs and 26 hard discs. Average duration of preoperative deltoid palsy was 11.9 weeks. Thirty-two patients underwent single-level surgery, 22 two-level, four three-level, and three four-level. Patients with accompanying myelopathy, shoulder diseases, or peripheral neuropathy were excluded from the study. Deltoid palsy (2.4 grades vs. 4.5 grades, p<0.001) and radiculopathy (6.4 points vs. 2.1 points, p<0.001) significantly improved after surgery. Thirty-six of 61 patients (59%) achieved full recovery (grade 5) of deltoid palsy, with an average time of 8.4 weeks. Longer duration of preoperative deltoid palsy and more severe radiculopathy negatively affected the degree of improvement in deltoid palsy. Age, gender, number of surgery level, and disc type did not affect the degree of improvement of deltoid palsy. Contrary to our expectations, severity of preoperative deltoid palsy did not affect the degree of improvement. Due to the shorter duration of preoperative deltoid palsy, in the context of rapid referral, early surgical decompression resulted in significant recovery of more severe grades (grade 0 or 1) of deltoid palsy compared to grade 2 or 3 deltoid palsy. Early surgical decompression significantly improved deltoid palsy caused by CDH, irrespective of age, gender, number of surgery level, and disc type. However, longer duration of deltoid palsy and more severe intensity of preoperative radiating pain were associated with less improvement of deltoid palsy postoperatively.


Carbon nanotube-MoS2 composites as solid lubricants.
Solid lubricants (SLs) characterized by low coefficients of friction (mu) and wear rates (w) drastically improve the life span of instruments that undergo extreme frictional wear. However, the performance of SLs such as sputtered or nanoparticulate molybdenum disulfide (MoS(2)), tungsten disulfide (WS(2)), or graphite deteriorates heavily under extreme operational conditions such as elevated temperatures and high humidity. Here, we present our preliminary results, which demonstrate that composites of carbon nanotubes (CNTs) and MoS(2) produced by electrodeposition of MoS(2) on vertically aligned CNT films have low mu ( approximately 0.03) and w (approximately 10(-13) mm(3)/N.mm) even at 300 degrees C, which are about 2 orders of magnitude better than those of nanoparticulate MoS(2)-based coatings. The high load-bearing capacity of CNTs provides a strong enduring support to MoS(2) nanoclusters and is responsible for their ultralow w. The incorporation of these composites in liquid lubricants reduces the friction coefficient of the liquid lubricants by approximately 15%. The technique described here to produce SL coatings with extremely appealing frictional properties will provide valuable solutions for a variety of tribological applications where the coatings encounter high temperature, reduced pressure, and/or low- and high-humidity conditions.


Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, India.
There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.


STAT3 promotes IFNγ/TNFα-induced muscle wasting in an NF-κB-dependent and IL-6-independent manner.
Cachexia is a debilitating syndrome characterized by involuntary muscle wasting that is triggered at the late stage of many cancers. While the multifactorial nature of this syndrome and the implication of cytokines such as IL-6, IFNγ, and TNFα is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNγ/TNFα promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both in vitro and in vivo independently of IL-6, which is considered as one of the main triggers of STAT3-mediated muscle wasting. pY-STAT3 forms a complex with NF-κB that is rapidly imported to the nucleus where it is recruited to the promoter of the iNos gene to activate the iNOS/NO pathway, a well-known downstream effector of IFNγ/TNFα-induced muscle loss. Together, these findings show that STAT3 and NF-κB respond to the same upstream signal and cooperate to promote the expression of pro-cachectic genes, the identification of which could provide effective targets to combat this deadly syndrome.


Impact of the COVID-19 Pandemic on Adult Mental Health.
The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.


The influence of sustained selective attention on stimulus selectivity in macaque visual area MT.
Remarkable alterations of perception during long-lasting attentional processes have been described in several recent studies. Although these findings have gained much interest, almost nothing is known about the modulation of neuronal responses during sustained attention. Therefore, we investigated the effect of prolonged selective attention on neuronal feature selectivity. Awake macaque monkeys were trained to perform a motion-tracking task that required attending one of two simultaneously presented moving bars for up to 15 sec. Extracellular recordings were obtained from neurons in macaque motion-sensitive middle temporal visual area (MT/V5). Under conditions of attention, we found high and constant direction selectivity over time. This was expressed by a strong and persistent response contrast between presentations of preferred and nonpreferred stimuli in successive motion cycles. With attention directed to another moving bar, neuronal responses to the behaviorally irrelevant stimulus became continuously less specific for the direction of motion. In particular, increasingly higher firing rates for motion in null direction caused a strong reduction of direction selectivity, which further increased with enhanced proximity between target and distracter bar. A passive condition experiment revealed that this reduction occurred only when motion remained the behaviorally relevant feature but disappeared when attention was withdrawn from this feature domain. Thus, sustained attention seems to stabilize direction selectivity of neurons in area MT against a time and competition-dependent degradation, whereas nonattended objects suffer from a reduced neuronal representation.


Conversion of glutamate into aspartate in guinea-pig cerebral-cortex slices.
1. When guinea-pig cerebral-cortex slices were incubated with [U-(14)C]glutamate as substrate, the specific radioactivities of the citric acid-cycle intermediates were lower than that of the aspartate isolated from the same vessels. 2. Aspartate was significantly labelled when [5-(14)C]glutamate was used as substrate and the aspartate contained almost no label when [1-(14)C]glutamate was present as substrate. 3. When specifically labelled glutamate was used as substrate, the label was found in the isolated aspartate in the position that would be predicted by citric acid-cycle mechanisms. 4. The results are consistent with the theory of ;compartmentation' of amino acid metabolism.


Use of monoclonal antibodies in renal transplantation.
Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects. However, an increase in long-term graft and patient survival has not been demonstrated yet. The B-cell-targeting antibody rituximab is used in blood group ABO-incompatible transplantation, in desensitization protocols, and for treatment of antibody-mediated rejection. Eculizumab interrupts the complement pathway and is a promising tool for the treatment of antibody-mediated rejection and post-transplant hemolytic-uremic syndrome. Future options are monoclonal antibodies with new molecular targets and antibodies that can be used for maintenance immunosuppression in order to avoid the toxicity of existing drugs. However, in several cases, the development of new monoclonal antibodies has been hampered by safety issues.


Thoracic Endovascular Aortic Repair for Type B Acute Aortic Dissection Complicated by Descending Thoracic Aneurysm.
To analyse the results and review the literature about thoracic aortic endovascular repair (TEVAR) for type B acute aortic dissection (TBAAD) complicated by descending thoracic aortic aneurysm (DTA) in the hyperacute or acute phases. This was a multicentre, observational descriptive study. Inclusion criteria were TBAAD with a DTA of ≥50 mm, TBAAD on an already known aneurysmal descending thoracic aorta, and TBAAD presenting with an enlarged aorta with a total diameter <50 mm, but with >50% diameter increase compared with a previous computed tomography angiography (CTA) showing a non-dissected aorta with normal sizing. Primary endpoints were early and long-term survival, freedom from TEVAR and aortic related mortality (ARM), and freedom from re-intervention. Twenty-two patients were included in the analysis. The mean aortic diameter was 66 ± 26 mm (range 42-130; IQR 51-64). The in hospital TEVAR related mortality was 14% (n = 3). The mean radiological follow-up was 56 ± 45 months (range 6-149; IQR 12-82), and the follow-up index 0.97 ± 0.1. All surviving patients were available for follow-up. During follow-up the cumulative mortality was 26% (n = 5) and TEVAR related mortality was 5% (n = 1). Overall the estimate of survival was 82% (95%CI: 61.5-93) at 1 year, and 64% at 5 years. Ongoing primary clinical success was 79% (re-intervention n = 4). Freedom from aortic related mortality was 86% (95%CI: 66-95) at 1 and 5 year, while freedom from re-intervention was 95% (95%CI: 75.5-95) at 1 year, and 77% (95%CI: 50-92) at 5 years. In our experience, DTA is a frequent complication from the very beginning of the clinical onset of TBAAD. In this high-risk cohort, TEVAR showed satisfactory results, better than those predicted by the risk score for open repair, with favourable stability of the aortic diameter and no aortic related adverse events during follow-up.


[Cardiac characteristics of patients with terminal renal failure after kidney transplantation].
Left ventricular (LV) hypertrophy and dysfunction are risk factors for high mortality from cardiovascular causes in patients with end-stage renal disease. To determine the frequency of these findings after kidney transplantation, 45 patients (11 female, 34 male; age: 47.2 +/- 12 years) after transplantation (57 +/- 37 months) with (n = 21) and without (n = 24) a patent arteriovenous fistula were analyzed with echocardiography. A high prevalence of systolic (> 140 mm Hg: 40%) and diastolic (> 90 mm Hg: 18%) hypertension was observed despite the use of 1.44 +/- 0.9 (range: 0-3) antihypertensive drugs per patient. Most frequent echocardiographic findings were LV hypertrophy (78%; LV mass = 318 +/- 81 g), mostly in the asymmetric septal form (47%; mean ratio septal/posterior wall thicknesses: 1.38 +/- 0.2), and left atrial dilatation (60%; mean diameter: 44 +/- 6 mm). LV dilatation (33%; mean enddiastolic diameter: 53 +/- 5 mm) and systolic dysfunction (20%; mean ejection fraction: 64 +/- 11%) were less common. Individual values of LV mass were directly correlated with systolic blood pressure (p < 0.05). No relation was found between other echocardiographic (LV and left atrial diameters, LV mass, ejection fraction or velocity of circumferential fibre shortening) and clinical (transplantation duration, serum hemoglobin or creatinine, patency of dialysis access, or choice of immunosuppressive therapy) parameters. The presented data suggest that LV hypertrophy is frequent after renal transplantation, and that arterial hypertension is a key factor for the maintenance of LV hypertrophy in these patients, while the patency of the dialysis access, and the durations of transplantation or of preceding dialysis therapy are not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)


Conserved Outer Tegument Component UL11 from Herpes Simplex Virus 1 Is an Intrinsically Disordered, RNA-Binding Protein.
A distinguishing morphological feature of all herpesviruses is the multiprotein tegument layer located between the nucleocapsid and lipid envelope of the virion. Tegument proteins play multiple roles in viral replication, including viral assembly, but we do not yet understand their individual functions or how the tegument is assembled and organized. UL11, the smallest tegument protein, is important for several distinct processes in replication, including efficient virion morphogenesis and cell-cell spread. However, the mechanistic understanding of its role in these and other processes is limited in part by the scant knowledge of its biochemical and structural properties. Here, we report that UL11 from herpes simplex virus 1 (HSV-1) is an intrinsically disordered, conformationally dynamic protein that undergoes liquid-liquid phase separation (LLPS) in vitro Intrinsic disorder may underlie the ability of UL11 to exert multiple functions and bind multiple partners. Sequence analysis suggests that not only all UL11 homologs but also all HSV-1 tegument proteins contain intrinsically disordered regions of different lengths. The presence of intrinsic disorder, and potentially, the ability to form LLPS, may thus be a common feature of the tegument proteins. We hypothesize that tegument assembly may involve the formation of a biomolecular condensate, driven by the heterogeneous mixture of intrinsically disordered tegument proteins.IMPORTANCE Herpesvirus virions contain a unique tegument layer sandwiched between the capsid and lipid envelope and composed of multiple copies of about two dozen viral proteins. However, little is known about the structure of the tegument or how it is assembled. Here, we show that a conserved tegument protein UL11 from herpes simplex virus 1, a prototypical alphaherpesvirus, is an intrinsically disordered protein that undergoes liquid-liquid phase separation in vitro Through sequence analysis, we find intrinsically disordered regions of different lengths in all HSV-1 tegument proteins. We hypothesize that intrinsic disorder is a common characteristic of tegument proteins and propose a new model of tegument as a biomolecular condensate.


Deep brain stimulation of the subthalamic nucleus in Parkinson's disease.
To evaluate the clinical effects of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease within the first 12 months after surgery. We performed a prospective study in 8 patients with Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus bilaterally. We compared levodopa-equivalents and the scores of the Unified Parkinson's Disease Rating Scale pre- and post-operatively. The post-operative evaluation was done between 3 and 12 months after surgery. Antiparkinsonian medications were reduced post-operatively by a mean of 61.5% (P < 0.01) from a levodopa-equivalent dosage of 1144.9 +/- 572.5 mg/day to 440.9 +/- 172.1 mg/day. Motor scores improved 44.4% (P < 0.01) and activities of daily living scores 38.2% (P < 0.01). Adverse events included a subcutaneous hematoma in 1 patient after internal pulse generator implantation necessitating evacuation. Bilateral stimulation of the subthalamic nucleus is associated with significant improvement in motor function and reduction of antiparkinsonian medications in patients with Parkinson's disease in the first 12 months after surgery. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medications. The procedure is well tolerated.


In-hospital Outcomes of Patients with ST-segment Elevation Myocardial Infarction who were Intubated before Primary Percutaneous Intervention: Experience of a tertiary center.
ST-segment elevation myocardial infarction (STEMI) complicated by respiratory failure is associated with a greater number of in-hospital and out-of-hospital adverse cardiovascular events (CVEs). The aim of this study was to analyze in-hospital outcomes and the factors affecting the outcomes of intubated patients diagnosed with STEMI who underwent primary percutaneous coronary intervention (pPCI) at a single tertiary care center. The data of 592 patients diagnosed with acute STEMI who were admitted to the emergency department between May 2017 and January 2019 and subsequently underwent pPCI were retrospectively reviewed. Cardiovascular risk factors as well as biochemical and angiographic characteristics of patients who were intubated in the emergency room or ambulance due to cardiac arrest and those who were not intubated were compared. Adverse CVEs were defined as in-hospital death, cerebrovascular stroke, and acute stent thrombosis. A total of 60 patients (70% male; mean age: 63.6±14.0 years) who were intubated and 532 non-intubated patients (81% male; mean age: 60.2±12.1 years) were included in the study. The angiographic features of the 2 groups were similar. An adverse CVE was experienced by 43.3% of the intubated patients and 3.6% of the non-intubated patients. Multivariate analysis indicated that age (odds ratio [OR]: 1.065; p<0.001), serum lactate level (OR: 1.308; p<0.001), and left ventricle ejection fraction (OR: 0.946; p<0.001) were independent predictors of in-hospital adverse CVE in the intubated patient group. The results of this single-center study showed that 1 in 10 patients hospitalized with STEMI were intubated, and approximately 4 in 10 intubated STEMI patients had an in-hospital CVE.


Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics.
This year in Galveston, Texas, Silvia Pierangeli hosts the 13th International Congress on Antiphospholipid Antibodies. Twenty-six years after the first antiphospholipid syndrome meeting, the number of interested colleagues has multiplied, and the subject has become more scientifically understood. So also has the clinical picture. In this short contribution, I will highlight a number of clinical observations which may, or may not, contribute to our understanding of antiphospholipid syndrome.


Reduced oxygen tension culturing conditionally alters toxicogenic response of differentiated H9c2 cardiomyoblasts to acrolein.
Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO2, translating to a culture oxygen tension of approximately 20%, far above most physiological tissues. The purpose of this investigation was to examine whether low-serum, retinoic acid differentiated H9c2 cells were less sensitive to acrolein insult when cultured under reduced oxygen tension. H9c2 cells were maintained separately in 20% and 5% oxygen, differentiated for 5 d, and then exposed to acrolein for 30 min in media containing varying concentrations of tricarboxylic acid and glycolytic substrates, followed by fresh medium replacement. Cells were then assessed for MTT reduction at 2 h and 24 h after acrolein insult. We showed that pyruvate supplementation in combination with lowered oxygen culturing significantly attenuated acrolein-induced viability loss at 24 h. Poly(ADP-ribose) polymerase inhibition and EGTA preferentially provided partial rescue to low oxygen cultures, but not for standard cultures. Collectively, these results offer evidence supporting altered toxicogenic response of H9c2 during physiologically relevant oxygen tension culturing.


Inhibitory Effect of Mesenchymal Stem Cell Co-Culture on Erythroid Differentiation of K562 Cells Compared to The Control Group.
Bone marrow mesenchymal stem cells (BMMSCs) reside in the bone marrow and control the process of hematopoiesis. They are an excellent instrument for regenerative treatment and co-culture with hematopoietic stem cells (HSCs). In this experimental study, K562 cell lines were either treated with butyric acid and co-cultured with MSCs, or cultivated in a conditioned medium from MSCs plus butyric acid for erythroid differentiation. We used the trypan blue dye exclusion assay to determine cell counts and viability in each group. For each group, we separately assessed erythroid differentiation of the K562 cell line with Giemsa stain under light microscopy, expression of specific markers of erythroid cells by flowcytometry, and erythroidspecific gene expressions by real-time polymerase chain reaction (RT-PCR). There was enhandced erythroid differentiation of K562 cells with butyric acid compared to the K562 cell line co-cultured with MSCs and butyric acid. Erythroid differentiation of the K562 cell line cultivated in conditioned medium with butyric acid was higher than the K562 cell line co-cultured with MSCs and butyric acid, but less than K562 cell line treated with butyric acid only. Our results showed that MSCs significantly suppressed erythropoiesis. Therefore, MSCs would not be a suitable optimal treatment strategy for patients with erythroid leukemia.


Primary subacute osteomyelitis of the greater trochanter.
Primary subacute osteomyelitis is difficult to diagnose, because of its insidious onset, mild symptoms, lack of a systemic reaction, and similarity with tumoral conditions. This condition is seen mostly in the epiphysis or metaphysis of tibia. Although it has been reported at various bones, its occurrence in the greater trochanter is rare. We describe two patients, 4 and 14 years old, with mild pain of the hip joint and limping without history of acute bone infection. Radiography showed a lytic lesion in the greater trochanter resembling Brodie abscess. Both patients were treated completely with antibiotics.


Highly selective transition-metal-free transamidation of amides and amidation of esters at room temperature.
Amide chemistry has an essential role in the synthesis of high value molecules, such as pharmaceuticals, natural products, and fine chemicals. Over the past years, several examples of transamidation reactions have been reported. In general, transition-metal-based catalysts or harsh conditions are employed for these transformations due to unfavorable kinetics and thermodynamics of the process. Herein, we report a significant advance in this area and present the general method for transition-metal-free transamidation of amides and amidation of esters by highly selective acyl cleavage with non-nucleophilic amines at room temperature. In contrast to metal-catalyzed protocols, the method is operationally-simple, environmentally-friendly, and operates under exceedingly mild conditions. The practical value is highlighted by the synthesis of valuable amides in high yields. Considering the key role of amides in various branches of chemical science, we envision that this broadly applicable method will be of great interest in organic synthesis, drug discovery, and biochemistry.


Using event-related potentials to measure phrase boundary perception in English.
The closure positive shift (CPS) event related potential (ERP) is commonly used as a neural measure of phrase boundary perception in speech. The present study investigated whether the CPS was elicited by acoustic cues at phrase boundaries in English. ERPs were recorded when participants listened passively to sentences with either early or late phrase boundaries. The closure positive shift (CPS) ERP was elicited at both early and late phrase boundaries. However, the latency, amplitude, and scalp distribution of these passive CPS ERPs in English sentences differed to active CPS ERPs measured in non-English sentences in previous studies. These results show that acoustic cues at the phrase boundaries in English are sufficient to elicit the CPS, and suggest that different processes might be involved in the generation of the CPS in active and passive conditions.


Maternal characteristics influencing the development of gestational diabetes in obese women receiving 17-alpha-hydroxyprogesterone caproate.
Gestational diabetes (GDM) and obesity portend a high risk for subsequent type 2 diabetes. We examined maternal factors influencing the development of gestational diabetes (GDM) in obese women receiving 17-alpha-hydroxyprogesterone caproate (17OHPC) for preterm delivery prevention. Retrospectively identified were 899 singleton pregnancies with maternal prepregnancy body mass indices of ≥30 kg/m(2) enrolled for either 17OHPC weekly administration (study group) or daily uterine monitoring and nursing assessment (control group). Patients with history of diabetes type 1, 2, or GDM were excluded. Maternal characteristics were compared between groups and for women with and without development of GDM. A logistic regression model was performed on incidence of GDM, controlling for significant univariate factors. The overall incidence of GDM in the 899 obese women studied was 11.9%. The incidence of GDM in the study group (n = 491) was 13.8% versus 9.6% in the control group (n = 408) (P = 0.048). Aside from earlier initiation of 17OHP and advanced maternal age, other factors including African American race, differing degrees of obesity, and use of tocolysis were not significant risks for the development of GDM. In obese women with age greater than 35 years, earlier initiation of 17OHPC may increase the risk for GDM.


Estrogens in vascular biology and disease: where do we stand today?
Whereas hormone therapy may increase the risk of coronary heart disease and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol. There is also evidence for a thrombogenic effect of oral estrogens. An understanding of the deleterious and beneficial effects of estrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas estradiol favors an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo involving several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for estrogens, since estradiol potentiates endothelial nitric oxide and prostacyclin production. The respective actions of estrogens on these cell populations may be influenced by the timing of hormonal therapy initiation, hormone regimens, status of the vessel wall and expression of isoforms of estrogen receptors alpha and beta. A better understanding of the balance between the deleterious and beneficial effects of estrogens is required and should help to improve hormonal therapy safety and to optimize the prevention of cardiovascular disease after menopause.


Oligodendrocyte ablation as a tool to study demyelinating diseases.
Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.


The importance of patient-centred care to overcome barriers in the management of actinic keratosis.
Visible actinic keratosis (AK) lesions and subclinical (non-visible) sun damage in the field of cancerization are associated with risk of both non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and, more rarely, melanoma. As the incidences of AK and skin cancer are increasing, effective prevention and treatment of AK is essential to minimize disease burden and improve patient quality of life. Currently, AK lesions are often left untreated and field therapies are underused. Patient-centred care, with a focus on the patient-physician relationship, has proven cost-effective, and improved clinical outcomes and patient satisfaction in a number of therapy areas. Strategies for applying patient-centred care to AK are warranted. Existing barriers to the effective treatment of AK were identified and patient-centric strategies to overcome each barrier were discussed. Barriers to effective AK treatment include poor disease awareness (for both patient and physician), concerns associated with the cosmetic effects of treatment, treatment-related side effects, cost perceptions for lesion-directed vs field-directed therapies, and inadequate adherence, particularly with long treatment duration. Overcoming these barriers will involve patient and physician education that promotes: disease prevention and awareness; the importance of self-examination; an understanding of treatment options; and the importance of adherence to treatment. To maximize its effectiveness, education should be delivered within a patient-centric framework, where the relationship between patient and physician is built on effective communication, empathy and a feeling of partnership. Patient-centric care, including patient education, is key to overcoming the barriers associated with effective AK treatment.


Sensitive electrochemical immunosensor for matrix metalloproteinase-3 based on single-wall carbon nanotubes.
A novel electrochemical immunosensor for the detection of matrix metalloproteinase-3 (MMP-3), a cancer biomarker protein, based on vertically aligned single-wall carbon nanotube (SWCNT) arrays is presented. Detection was based on a sandwich immunoassay consisting of horseradish peroxidase (14-16 labels) conjugated to a secondary antibody and/or a polymer bead loaded with multi-enzyme labels. Performance was optimized by effective minimization of non-specific binding (NSB) events using Bovine serum albumin (BSA), Tween-20 and optimization of the primary antibody and secondary antibody concentrations. Results provided a detection limit of 0.4 ng mL(-1) (7.7 pM) for the 14-16 label sensor protocol and 4 pg mL(-1) (77 fM) using a multiply enzyme labeled polymeric bead amplification strategy in 10 microL of calf serum. This immunosensor based on SWCNT arrays offers great promise for a rapid, simple, cost-effective method for clinical screening of cancer biomarkers for point-of-care diagnosis.


Manipulation of Gut Microbiota Influences Immune Responses, Axon Preservation, and Motor Disability in a Model of Progressive Multiple Sclerosis.
Gut microbiota dysbiosis has been implicated in MS and other immune diseases, although it remains unclear how manipulating the gut microbiota may affect the disease course. Using a well-established model of progressive MS triggered by intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), we sought to determine whether dysbiosis induced by oral antibiotics (ABX) administered on pre-symptomatic and symptomatic phases of the disease influences its course. We also addressed the effects of microbiota recolonization after ABX withdrawn in the presence or absence of probiotics. Central and peripheral immunity, plasma acetate and butyrate levels, axon damage and motor disability were evaluated. The cocktail of ABX prevented motor dysfunction and limited axon damage in mice, which had fewer CD4+ and CD8+ T cells in the CNS, while gut microbiota recolonization worsened motor function and axonal integrity. The underlying mechanisms of ABX protective effects seem to involve CD4+CD39+ T cells and CD5+CD1d+ B cells into the CNS. In addition, microglia adopted a round amoeboid morphology associated to an anti-inflammatory gene profile in the spinal cord of TMEV mice administered ABX. The immune changes in the spleen and mesenteric lymph nodes were modest, yet ABX treatment of mice limited IL-17 production ex vivo. Collectively, our results provide evidence of the functional relevance of gut microbiota manipulation on the neurodegenerative state and disease severity in a model of progressive MS and reinforce the role of gut microbiota as target for MS treatment.


The effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on the OCT-measured macular choroidal thickness of eyes with proliferative diabetic retinopathy.
To investigate the effect of laser pan-retinal photocoagulation with or without intravitreal bevacizumab injections on macular choroidal thickness parameters in eyes with high-risk proliferative diabetic retinopathy. High-risk proliferative diabetic retinopathy patients undergoing laser treatment were prospectively enrolled in this study. One eye was randomly selected for laser treatment combined with bevacizumab injections, study group, whereas the corresponding eye was subjected to laser treatment alone, control group. Spectral-domain optical coherence tomography with enhanced depth imaging was used to measure the macular choroidal thickness prior to and 1 month after treatment. Measurements in both groups were compared. Clinicaltrials.gov: NCT01389505. Nineteen patients (38 eyes) with a mean±standard deviation age of 53.4±9.3 years were evaluated, and choroidal thickness measurements for 15 patients were used for comparison. The greatest measurement before treatment was the subfoveal choroidal thickness (341.68±67.66 μm and 345.79±83.66 μm for the study and control groups, respectively). No significant difference between groups was found in terms of macular choroidal thickness measurements at baseline or after treatment. However, within-group comparisons revealed a significant increase in choroidal thickness parameters in 10 measurements in the study group and in only 5 temporal measurements in the control group when 1-month follow-up measurements were compared to baseline values. The macular choroidal thickness does not appear to be significantly influenced by laser treatment alone but increases significantly when associated with bevacizumab injections in patients with proliferative diabetic retinopathy and macular edema. Because bevacizumab injections reduce short-term laser pan-retinal photocoagulation-induced macular edema, our findings suggest that the choroid participates in its pathogenesis.


Determinants for hospitalisations, intensive care unit admission and death among 20,293 reported COVID-19 cases in Portugal, March to April 2020.
BackgroundDeterminants of hospitalisation, intensive care unit (ICU) admission and death are still unclear for COVID-19. Few studies have adjusted for confounding for different clinical outcomes including all reported cases within a country.AimWe used routine surveillance data from Portugal to identify risk factors for severe COVID-19 outcomes, and to support risk stratification, public health interventions, and planning of healthcare resources.MethodsWe conducted a retrospective cohort study including 20,293 laboratory-confirmed cases of COVID-19 reported between 1 March and 28 April 2020 through the national epidemiological surveillance system. We calculated absolute risk, relative risk (RR) and adjusted relative risk (aRR) to identify demographic and clinical factors associated with hospitalisation, ICU admission and death using Poisson regressions.ResultsIncreasing age (≥ 60 years) was the major determinant for all outcomes. Age ≥ 90 years was the strongest determinant of hospital admission (aRR: 6.1), and 70-79 years for ICU (aRR: 10.4). Comorbidities of cardiovascular, immunodeficiency, kidney and lung disease (aRR: 4.3, 2.8, 2.4, 2.0, respectively) had stronger associations with ICU admission, while for death they were kidney, cardiovascular and chronic neurological disease (aRR: 2.9, 2.6, 2.0).ConclusionsOlder age was the strongest risk factor for all severe outcomes. These findings from the early stages of the COVID-19 pandemic support risk-stratified public health measures that should prioritise protecting older people. Epidemiological scenarios and clinical guidelines should consider this, even though under-ascertainment should also be considered.


Automatic and controlled verbal-information processing in patients with frontal lobe lesions.
The selectivity of frontal lobe lesion effects in the domains of verbal-information processing has not been well established. The authors hypothesized that capacity-limited controlled processing would be more impaired than automatic processing in frontal lobe patients (FLPs). Fifteen FLPs were compared with 2 matched control groups: 14 posterior-lesion patients and 15 normal controls. Both behavioral and event-related brain potential (ERP) measures were collected. Results suggest that both automatic and controlled processing were affected by frontal lobe lesions. ERP results indicated that the main dificulty for the FLPs was in the perceptual stage of information processing. This rather unexpected result may be explained by a basic difficulty of FLPs in attending to a new stimulus in order to process it.


Buerger's disease.
Buerger's disease (thromboangiitis obliterans) is rarely seen in most clinical practices. Many advanced practice nurses may only see one or two cases in their lifetime, and some hospital-based nurses may never see the disease. Information about this occlusive peripheral arterial disease must be obtained for the vascular nurse to care for patients with the disease. The subject of Buerger's disease is not common in the literature, and little is found in nursing texts or journals. The care of the disease involves nursing emphasis on lifestyle changes. This article will address definition, history, review of literature, and pathophysiology. The recommendations for diagnosis, treatment, and nursing care interventions also will be reviewed.


Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?
Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies.


Growth charts for Saudi children and adolescents.
To establish reference growth charts for Saudi children and adolescents. Multi-stage probability sampling of a cross-section of Saudi children and adolescents residing in all 13 regions of the Kingdom. Family interviews, and physical examinations of children and adolescents from birth to 19 years of age were conducted over a 2-year period (2004-2005). Only healthy children and adolescents were included for the measurement of length/stature, weight, and head circumference. All measurements were performed by trained physicians and nurses according to World Health Organization guidelines. Percentile construction and smoothing were performed using the LMS (lambda, mu, sigma) methodology. Determination of the standard measures for normal physical growth in a sample representing healthy Saudi children and adolescents from birth to 19 years of age. The results of this study present the most comprehensive and up-to-date reference growth charts for Saudi children and adolescents. Therefore, the authors recommend the use of these charts to replace older charts or those belonging to other countries.


Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods.
Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220-290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using 'MAPLE V' software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.


Profiling the microbial contamination in aviation fuel from an airport.
Microbial contamination during fuel storage can cause fuel system fouling and corrosion. Characterizing microbial contamination is critical for preventing and solving these problems. In this study, culture-based combing with the culture-independent methods, were used to profile the microbial contamination in aviation fuel. High-throughput sequencing (HTS) modified by propidium monoazide (PMA) revealed a higher diversity of contaminating microorganisms in samples than the culture method. Proteobacteria (47%), Actinobacteria (21%) and Ascomycota (>99%, fungi) were the most abundant phyla, and the neglected archaea was also detected. Additionally, qPCR-based methods revealed all samples contained a heavy level of microbial contamination, which was more accurate than its culturable counterparts, and fungal contamination was still a problem in aviation fuel. The application of a PCR-based method gives deeper insight into microbial contamination in aviation fuel than the conventional culture method, thus using it for regular detection and accurate description of fuel contamination is strongly recommended in the case of explosive microbial growth.


Donor-But Not Recipient-Derived Cells Produce Collagen-1 in Chronically Rejected Cardiac Allografts.
Fibrosis is a prominent feature of chronic allograft rejection, caused by an excessive production of matrix proteins, including collagen-1. Several cell types produce collagen-1, including mesenchymal fibroblasts and cells of hematopoietic origin. Here, we sought to determine whether tissue-resident donor-derived cells or allograft-infiltrating recipient-derived cells are responsible for allograft fibrosis, and whether hematopoietic cells contribute to collagen production. A fully MHC-mismatched mouse heterotopic heart transplantation model was used, with transient depletion of CD4+ T cells to prevent acute rejection. Collagen-1 was selectively knocked out in recipients or donors. In addition, collagen-1 was specifically deleted in hematopoietic cells. Tissue-resident macrophages were depleted using anti-CSF1R antibody. Allograft fibrosis and inflammation were quantified 20 days post-transplantation. Selective collagen-1 knock-out in recipients or donors showed that tissue-resident cells from donor hearts, but not infiltrating recipient-derived cells, are responsible for production of collagen-1 in allografts. Cell-type-specific knock-out experiments showed that hematopoietic tissue-resident cells in donor hearts substantially contributed to graft fibrosis. Tissue resident macrophages, however, were not responsible for collagen-production, as their deletion worsened allograft fibrosis. Donor-derived cells including those of hematopoietic origin determine allograft fibrosis, making them attractive targets for organ preconditioning to improve long-term transplantation outcomes.


Thrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy.
A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin.


Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors.
Several Toll-like receptors (TLRs) are expressed in Sertoli cells and can trigger testicular innate responses after activation by ligands. TLR signaling pathway must be tightly controlled because unrestrained TLR activation generates a chronic inflammatory milieu that often leads to pathogenesis of the host. However, the regulation of TLR signaling in Sertoli cells remains to be clarified. Here we demonstrate that Tyro3 subfamily of receptor tyrosine kinases, Tyro3, Axl, and Mer (TAM), negatively regulate TLR3 signaling in Sertoli cells. Sertoli cells from TAM triple mutant (TAM(-/-)) mice exhibit an excessive activation of TLR3 in response to its ligand polyinosinic-polycytidylic acid, resulting in the up-regulation of inflammatory cytokines including IL-1beta, IL-6, TNFalpha, and type I interferons (alpha and beta). Growth arrest-specific gene 6 (Gas6), a common ligand of TAM receptors, inhibits the TLR3-driven expression of cytokines in Sertoli cells. This TAM-mediated inhibition of TLR3 signaling in Sertoli cells is transduced through the up-regulation of TLR signaling suppressors suppressor of cytokine signaling-1/3 by Gas6. Moreover, we provide evidence that TAM inhibition of inflammatory cytokine production by Sertoli cells may have physiological significance in vivo. These results illuminate a negative regulatory mechanism of TLR3 signaling in Sertoli cells, which may participate in controlling the testicular innate immune responses to pathogens.


Right Ventricle and Autoimmune Diseases.
Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.


Comparison of backbone dynamics of apo- and holo-acyl-coenzyme A binding protein using 15N relaxation measurements.
15N magnetic relaxation parameters T1, T2 and the nuclear Overhauser effect in the protein acyl-coenzyme A binding protein (ACBP) have been measured in the presence and absence of the ligand, palmitoyl-coenzyme A, in order to obtain information about local and global dynamical properties of the peptide backbone with and without the ligand bound in the binding site. The three-dimensional structures of acyl-coenzyme A binding protein are known for both states of the protein as determined from multidimensional heteronuclear NMR studies, and they have been shown to be essentially identical. However, the dynamics of the backbone is influenced by the presence of ligand in the binding site. The binding of ligand had significant and specific effects on the relaxation time T1 for many of the 15N in the peptide backbone, in particular those near residues with contacts to the ligand. Similarly, the nuclear Overhauser effect at 15N near such residues increased. There were no significant changes in the T2 relaxation. T1 values showing a significant decrease and NOEs increasing in regions close to the binding site when the ligand was bound suggest two modes of action on the dynamics of the protein when the ligand is binding. The reduced T1 indicates motion of lower amplitude in agreement with the structural constraints introduced by protein-ligand interactions. The increased NOEs may be a consequence of shorter time constants for dynamics of the atoms close to the binding site. The Lipari-Szabo model could not be satisfactorily applied to the entire set of experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)


Expanding the evidence for health promotion: developing best practices for WISEWOMAN.
Implementing effective programs to prevent chronic disease holds the promise of reducing morbidity and mortality, reducing health disparities, and promoting health. Yet many programs have demonstrated success only in highly controlled research settings and few address the needs of low-income, uninsured, minority women. Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN), a demonstration program funded by the Centers for Disease Control and Prevention (CDC), that provides chronic disease risk factor screening and lifestyle interventions for low-income, 40-64-year-old women is learning from our own successful programs but is also charting new territory. As the CDC, state health departments, tribal organizations, and other WISEWOMAN partners approach the end of the first decade of WISEWOMAN demonstration projects, we are seeking to understand what has worked and what has not. This paper describes the rationale and proposed methodology for assessing best practices in the WISEWOMAN program through a participatory process that will examine scientific evidence and quantitative and qualitative program data. By emphasizing practicality in addition to scientific rigor, we are expanding the base of evidence considered to identify effective approaches for reducing cardiovascular disease (CVD) risk in financially disadvantaged, ethnically diverse women. Results of the 3-year project will be disseminated in a format intended to encourage programs to select and adapt those strategies best suited to their particular contexts.


[Clinical application of deep lamellar keratoplasty for corneal macula after viral keratitis].
To explore the clinical safety and efficacy of deep lamellar keratoplasty for corneal macula after viral keratitis. A total of 16 patients (16 eyes) of corneal macula after viral keratitis at our center from January 2009 to June 2011 received anti-virus eye-drops and then underwent deep lamellar keratoplasty when inflammation were dissolved or quiescent. And the corneal graft diaphaneity and corneal graft rejection reactions were observed. All 16 patients were recovered with a success rate of 100%. After a follow-up of 18-24 months, all corneal grafts were transparent and best-corrected visual acuity was 0.2-0.6. There was no reoccurrence during the follow-up period. After a follow-up of several months, 2 of them had rejection reaction and were controlled after treatment. No rejection reaction occurred during the long-term follow-up. As a safe and efficacious procedure, deep lamellar keratoplasty can significantly raise vision acuity with few complications.


Redox signalling and cardioprotection: translatability and mechanism.
The morbidity and mortality from coronary artery disease (CAD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of culprit coronary arteries. Although it is mandatory to reperfuse the ischaemic territory as soon as possible, paradoxically this leads to additional myocardial injury, namely ischaemia/reperfusion (I/R) injury, in which redox stress plays a pivotal role and for which no effective therapy is currently available. In this review, we report evidence that the redox environment plays a pivotal role not only in I/R injury but also in cardioprotection. In fact, cardioprotective strategies, such as pre- and post-conditioning, result in a robust reduction in infarct size in animals and the role of redox signalling is of paramount importance in these conditioning strategies. Nitrosative signalling and cysteine redox modifications, such as S-nitrosation/S-nitrosylation, are also emerging as very important mechanisms in conditioning cardioprotection. The reasons for the switch from protective oxidative/nitrosative signalling to deleterious oxidative/nitrosative/nitrative stress are not fully understood. The complex regulation of this switch is, at least in part, responsible for the diminished or lack of cardioprotection induced by conditioning protocols observed in ageing animals and with co-morbidities as well as in humans. Therefore, it is important to understand at a mechanistic level the reasons for these differences before proposing a safe and useful transition of ischaemic or pharmacological conditioning. Indeed, more mechanistic novel therapeutic strategies are required to protect the heart from I/R injury and to improve clinical outcomes in patients with CAD.


Basic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.
A two-site enzyme-linked immunosorbent assay was used to quantitate levels of basic fibroblast growth factor in the vitreous from 36 patients undergoing vitrectomy for a variety of retinal conditions, including proliferative diabetic retinopathy, macular pucker, and retinal detachment with and without proliferative vitreoretinopathy. Basic fibroblast growth factor levels ranged from undetectable to 52 ng/mL. In patients with proliferative diabetic retinopathy, basic fibroblast growth factor levels were greater than or equal to 30 ng/mL in 8 of 17 specimens. Of the 8 patients with elevated basic fibroblast growth factor levels, 6 had evidence of active proliferative disease (ie, neovascularization of the disc or iris), whereas in the patients who had undetectable levels only 2 of 9 had evidence of neovascularization of disc and none had neovascularization of the iris. In the rhegmatogenous retinal detachment group, 2 of 10 eyes had elevated basic fibroblast growth factor levels, while none in the macular pucker group had elevated levels. Our study documents increased levels of basic fibroblast growth factor in vitreous specimens from patients with proliferative diabetic retinopathy, particularly those with active proliferative retinopathy. The role of basic fibroblast growth factor in the pathogenesis of various retinal disease entities is discussed.


A child with imperforate anus for twelve years: a case report of neglect and exploitation.
We report a unique and rare case of child neglect and exploitation and similar case was not found. An infant, born with an imperforate anus, underwent surgery for a temporary colostomy on the day of birth. Surgery for reversal of colostomy with reconstruction was planned at one month of age. However, the guardian did not ensure that the child attended for this procedure. Subsequently, at the age of 12 years, the child was presented to the emergency unit with an irreducible prolapsed colostomy and a life threatening acute abdomen. Emergency laparotomy and colostomy reversal were performed with anal reconstruction. The child had features of gross neglect and abuse in the form of deprivation of essential surgical care, vaccination, and education. He was used for the purpose of begging for the financial benefit of his guardian and others. This is a case of neglect and exploitation of a child with imperforate anus and it emphasizes the failures of the health system to manage and follow-up children with congenital defects born to families with a poor socio-economic background.


Intrapartum risk factors for permanent brachial plexus injury.
The purpose of this study was to compare maternal, neonatal, and second stage of labor characteristics in shoulder dystocia deliveries that result in permanent brachial plexus injury with shoulder dystocia deliveries that result in no injury. Our cases were culled from a database of deliveries that resulted in permanent brachial plexus injuries and matched to control cases that were taken from a database of consecutive shoulder dystocia deliveries from one hospital. Deliveries that resulted in injury were excluded from the control cases; those cases with no recorded shoulder dystocia were excluded from the cases. Matching was for birth weight (+/-250 g), parity, and diabetic status. Rates of precipitous and prolonged second stage, operative delivery, neonatal depression, and average number of shoulder dystocia maneuvers used were compared between the two groups with chi(2) test, Fisher exact test, and the Student t test; a probability value of <.05 was considered significant. There were 80 matched patients, of which 26 patients were nulliparous and 11 patients were diabetic. Mothers of the uninjured group were younger than those of the injured group (23.7+/-6.2 years vs 27.4+/-5.1 years, P<.001). The injured group had a significantly higher rate of 5-minute Apgar scores of <7 (13.9% vs 3.8%, P=.04). Differences in maternal weight, body mass index, height, race, gestational age, average number of maneuvers, head-to-body delivery interval, operative delivery rate, prolonged second stage rate, precipitous second stage rate, and sex were not significant between groups. The rates of precipitous second stage for both groups (28.0% injured and 35.0% uninjured) were more than triple the rates of prolonged second stage (9.5% injured and 11.3% uninjured). No characteristic of second-stage of labor predicts permanent brachial plexus injury. Precipitous second stage is the most prevalent labor abnormality that is associated with shoulder dystocia.


Comparison of the standard predictive equation for calculation of resting energy expenditure with indirect calorimetry in hospitalized and healthy dogs.
To determine the level of clinical agreement between 2 methods for the measurement of resting energy expenditure (REE). Prospective case series. 77 dogs. Oxygen consumption (Vo2) and CO2 production (Vco2) were measured with an open-flow indirect calorimeter in healthy (n = 10) and ill (67) dogs. Measurements were collected at 3 time periods on 2 days. The Vo2 and the Vco2 measurements were then used to calculate the REE values. Mean values of measured (MREE) and predicted (PREE) REEs in healthy dogs and a dog with medical illnesses or trauma were not significantly different. There was a significant difference on day 2 between the MREE and PREE in the group of dogs recovering from major surgery. More importantly, there was significant variation between the PREE and MREE on an individual-dog basis. The PREE only agreed to within +/- 20% of the MREE in 51% to 57% of the dogs. The level of agreement between these two methods for determining the 24-hour REE was poor in individual dogs. The level of disagreement between the 2 methods indicates that these methods may not be used interchangeably in a clinical setting. Measurement of REE by use of indirect calorimetry may be the only reliable method of determining REE in an individual ill or healthy dog.


Design of self-assembled glycopolymeric zwitterionic micelles as removable protein stabilizing agents.
Developing stabilizers that protect proteins from denaturation under stress, and are easy to remove from solutions, is a challenge in protein therapeutics. In this study, micelles made of trehalose, a zwitterionic polymer (poly-sulfobetaine; poly-SPB), and polycaprolactone (PCL) were synthesized by a one-pot reversible addition-fragmentation chain-transfer (RAFT) polymerization reaction. The micelles protect lactate dehydrogenase (LDH) and human insulin from denaturation due to stresses like thermal incubation and freezing, and help them retain higher-order structures. Importantly, the protected proteins are readily isolated from the micelles by ultracentrifugation, with over 90% recovery, and almost all enzymatic activity is retained. This suggests the great potential of poly-SPB-based micelles for use in applications requiring protection and removal as required. The micelles may also be used to effectively stabilize protein-based vaccines and drugs.


The oocyte population is not renewed in transplanted or irradiated adult ovaries.
According to conventional theory, the oocyte population is not renewed in mammalian ovaries after birth. A new hypothesis proposes that oocytes are generated continuously from haematopoietic progenitor cells. There is, however, no evidence that they can ovulate, although they may partially restore fertility by organizing 'helper follicles'. The hypothesis that follicles can form de novo in adult ovaries has been tested in a transplant model. Ovaries from adult mice were transplanted under the kidney capsule or into the ovarian bursa of histocompatible, transgenic CAG::H2B-EGFP host animals. Some donors were sterilized before transplantation by X-irradiation to ensure 'empty niches' were available for repopulation. The phenotype of follicular oocytes at 2, 4 and 8 weeks post-transplantation was scored by epifluorescence. A total of 819 oocytes were examined in 30 ovarian grafts. None expressed green fluorescence, as would be predicted if they had formed de novo from germ cell progenitors in the systemic circulation of the host. Furthermore, small follicles eliminated by irradiation were not replaced in transplanted ovaries, and the few growing follicles present were apparently survivors of the original population. No evidence was found to support the hypothesis that progenitor cells from extra-ovarian sources can repopulate the adult ovary. The findings are consistent with the conventional view that a limited number of oocytes are formed before birth and declines with age. The study did not, however, rule out the possibility that germline stem cells may reside in the adult ovary.


Bacteremia in Trauma: A Contemporary Analysis of Blood Culture Results and Outcomes in 158,884 Patients.
Background: Bacteremia is a potentially lethal complication. Limited research exists describing its incidence and associated outcomes in trauma patients. This descriptive study characterized the incidence, risk factors, and outcomes of bacteremia in trauma patients. Methods: This study used 2017-2020 system-wide Trauma Registry/Electronic Data Warehouse to select trauma activations aged ≥18 years. Blood culture information, including pathogen genera and species, was obtained from electronic laboratory records. Bacteremia positive was defined as two blood cultures within two hours of each other, growing the same organism; bacteremia negative as no growth, only one blood culture with growth, or growth of two different organisms. Bacteremia-positive and bacteremia-negative patients were compared with patients without blood cultures. Logistic regression compared blood culture results with outcomes, adjusting for age, gender, Injury Severity Score (ISS), and comorbidities. Results: Of 158,884 patients at 89 centers, 17,166 (10.8%) had blood cultures. Of those with blood cultures, 1214 were bacteremia positive (7.1%). Compared with no blood cultures, bacteremia-positive patients were more likely male, with higher ISS, and more comorbidities and intensive care unit use. Bacteremia-positive patients were more likely to die (adjusted odds ratio [aOR], 3.78; 95% confidence interval [CI], 3.17-4.51; p < 0.001) and have severe sepsis/septic shock (aOR, 114.91; 95% CI, 95.09-138.85; p < 0.001). Most common isolates were Staphylococcus epidermidis (14%), non-methicillin resistant Staphylococcus aureus (12%), and Escherichia coli (6%), with highest mortality associated with Pseudomonas aeruginosa (45%), Enterococcus faecalis (30%), and Escherichia coli (28%). Conclusions: Bacteremia in trauma is uncommon (<1%) but associated with increased resource use and poorer outcomes. Bacteremia, or suspicion thereof, identifies a high-risk population and justifies aggressive empiric intervention to maximize survival.


Protection of human amniotic epithelial cells (HAEC) from complement-mediated lysis: expression on the cells of three complement inhibitory membrane proteins.
Cultured human amniotic epithelial cells (HAEC) were found by immunofluorescence microscopy to express three complement inhibitory membrane proteins, CD59 antigen, decay-accelerating factor (DAF) and membrane attack complex (MAC) inhibitory protein (MIP), on their surfaces. The effects of incubation with Fab2 fragments of monoclonal antibodies (mAb) raised against these proteins on susceptibility of sensitized cells to lysis by homologous complement was examined. Percentage cell lysis was markedly increased in the presence of Fab2 anti-CD59 and to a lesser, but significant, extent in the presence of Fab2 anti-DAF. Fab2 anti-MIP did not alter the sensitivity of the cells to lysis by complement.


Continuous protein separations in a magnetically stabilized fluidized bed using nonmagnetic supports.
Continuous protein separations were performed using a magnetically stabilized fluidized bed (MSFB) and a commercially available affinity adsorption resin that contained no magnetically susceptible material. These nonmagnetic materials can be stabilized at relatively low fields (<75 G requiring <30 W) if sufficient magnetically susceptible particles are also present in the stabilized bed. The minimum amount of magnetic particles necessary to stabilize the bed is as low as 20% by volume and is a function of various parameters including the size and density of both particles, the magnetic field strength, and the fluidization velocity. Advantages of these beds for performing separations include true continuous, countercurrent liquid-solids contact, mass-transfer efficiencies nearly equal to that of packed beds, and the ability of handle suspended cells or cell debris. A variety of commercially available affinity, ion-exchange, and adsorptive supports can be used in the bed for continuous separations; results are presented for the adsorption and recovery of lysozyme from an aqueous mixture of lysozyme and myoglobin using an affinity resin.