Association of clot burden score with radiographic and clinical outcomes following Solitaire stent retriever thrombectomy: analysis of the SWIFT PRIME trial.
The clot burden score (CBS) was developed as a tool to evaluate the extent of intracranial thrombus burden in patients with anterior circulation acute ischemic stroke. CBS is based on the presence or absence of contrast opacification on CT angiography (CTA). Its value in predicting radiographic and clinical outcomes in patients given endovascular stroke therapy remains unknown. To evaluate the relationship between CBS and outcomes after stent retriever thrombectomy in the interventional arm of the SWIFT PRIME trial. CBS was calculated for the endovascular arm (IV tissue plasminogen activator plus Solitaire stent retriever) of SWIFT PRIME using baseline CTA. The cohort of 69 patients was divided into three groups according to their CBS values: CBS 0-5 (n=14), CBS 6-7 (n=23), and CBS 8-9 (n=32). The mean age of the 69 patients who formed the study cohort was 63.2±13.1 years, mean National Institutes of Health Stroke Scale score was 16.8±4.5, and 55% of the patients were male. There was no difference in clinical characteristics among the three groups, except for the baseline Alberta Stroke Program Early CT Score (p=0.049). The site of proximal occlusion varied significantly among the three groups (p<0.001). Rates of successful recanalization (TICI 2b/3), complete recanalization (TICI 3 only) and of good clinical outcome at 3 months were similar among the three groups (p=0.24, p=0.35, and p=0.52, respectively). The combination of IV thrombolysis and stent retriever thrombectomy with the Solitaire device is highly effective in achieving successful recanalization and a good clinical outcome throughout the entire range of CBS values.


Fetal cardiac output measured by four-way thermodilution.
To measure fetal cardiac output by thermodilution, we injected 2.5 ml of iced 5% glucose rapidly into the superior vena cava and recorded areas of temperature-time curves in the brachiocephalic artery (AS) and descending aorta (BS). One minute later we repeated the injection into the inferior vena cava and recorded areas under two curves (AI and BI). Cardiac output was calculated as Qco = H (AS + BI - AI - BS) (ASBI - AIBS), where H is the change in caloric content of the blood. In a mechanical model we found thermal results correlated well with timed collections (r = 0.98) with a slope of 0.995. In 7 acutely prepared fetal lambs, electromagnetic flow probe measurements of total cardiac output (descending aorta + brachiocephalic artery) correlated well (0.90) with thermal measurements. The slope (1.16) was significantly greater than 1.0, reflecting the inclusion of coronary and pulmonary flows in thermal, but not in flow probe, measurements. In 11 acutely and chronically prepared fetal lambs, the correlation between microsphere and thermal measurements was 0.81 with a slope of 1.09, not significantly different from 1.0. Hence, thermodilution gives results comparable to other methods and is convenient, indefinitely repeatable, inexpensive, and nonradioactive.


Health risk behavior pattern among students from Cartagena, Colombia: prevalence and associated variables.
The aim of the study was to determine the prevalence and variables associated with the pattern of risky health behavior (PRHB) among adolescent students in Cartagena, Colombia. A cross-sectional study was designed to investigate PRHB in a random cluster sample of students from middle and high schools. The associations were adjusted by logistic regression. A total of 2,625 students participated in this research, with ages from 10 to 20 years, mean=13.8 years (SD=2.0), and 54.3% were women. A total of 332 students reported PRHB (12.7%, 95%CI 11.4-14.0). Age over 15 years (OR=2.19, 95%CI 1.72-2.79), not being heterosexual (OR=1.98, 95%CI 1.36-2.87), poor/mediocre academic performance (OR=1.87, 95%CI 1.47-2.38), family dysfunction (OR=1.78, 95%CI 1.40-2.28) and male gender (OR=1.58, 95%CI 1.24-2.01) were associated with PRHB. One in every eight students presented a PRHB. It is important to pay greater attention to students who are over 15 years of age, male, not heterosexual, with a poor/mediocre academic performance and a dysfunctional family.


Workplace Bullying in Italy: A Systematic Review and Meta-Analysis.
Within any work environment, employees may be affected by "workplace bullying", a form of violent and repeated social behavior towards subordinates and colleagues. This review aimed to investigate the prevalence of bullied workers in Italy, the causes of the phenomenon, and the consequences at physical, psychological, and organizational levels. We included observational studies and systematic reviews examining the prevalence of bullied workers and the causes and consequences in Italian workplaces. Data extraction and analysis were performed on all included studies. The research strategy included three electronic databases (PubMed, Scopus, and Web of Science). A comprehensive search was done to retrieve articles based on a PRISMA-compliant protocol registered in PROSPERO: CRD 42023394635. One hundred eighty-four articles were retrieved, and once duplicates and irrelevant articles were removed, 42 useful articles were reviewed. The mean pooled prevalence, calculated based on workers complaining of mistreatment, was 6.7% (SD: 4,09) and increased significantly to 17.0% (SD: 12.88) when considering only healthcare workplaces. Causes include how impaired mental health and high workload reinforce the possibility of being bullied in the workplace, resulting in a worsening of the worker's quality of life (physical and psychological) and the work organization with increased absenteeism and job changes. Workplace bullying is a very present phenomenon within workplaces in Italy. In light of this, it is necessary to put prevention plans in place and find solutions to maintain optimal organizational well-being in the work environment.


Laparoscopic adnexal transposition: novel surgical technique.
Treatment of some cancers diagnosed at an early stage with expectation of prolonged survival has permitted the consideration of salvaging the reproductive and hormonal function of premenopausal female patients. When radiation to the pelvic area is part of treatment, this will almost always result in ovarian failure. To protect the ovaries, an oophoropexy may be performed, which involves moving the ovaries away from the radiation field. This procedure may be performed via laparoscopy. Some women undergoing laparoscopic radical hysterectomy may also be candidates for laparoscopic transposition. Because failure rates are still reported to be high, we developed a novel technique to mobilize the adnexa, which we present in this paper and attached movie.After separating the adnexa from the uterus and developing the infundibulopelvic (IP) ligament, a retroperitoneal tunnel is developed from the pelvis to the transposition opening laterally. The adnexa are moved through this tunnel, avoiding torsion of the vessels, and are brought through the opening back into the peritoneum. The adnexa are now fixed securely to the posterolateral abdominal wall with nonabsorbable sutures.Several issues permit better results using this technique. The IP ligament remains retroperitoneal and itself is outside the field of radiation. There is no kinking of the ovarian blood supply on the peritoneal fold. The location of the transposition is way above the field of radiation, preventing scatter injury. Even if one or both of the sutures fail, placement of the ovary will not change because of the peritoneum it has been brought through. This and the final location of the IP ligament retroperitoneally may enforce the ovary to it outside of the radiation field and prevent possible migration of the ovary back to the pelvis. This technique has advantages, which may offer the ovaries a better chance to resume hormonal function.


[The epidemiological and clinicoimmunological aspects of the outburst of trichinosis in the Krymsky District of the Krasnodar Territory].
The present paper presents the epidemiological and clinicoimmunological aspects of the outburst of trichinosis in the Krymsky District of the Krasnodar Territory in January 2001. Six hundred and forty-eight persons ate infested wild boar meat, 119 (74.8%) fell ill with moderate and severe trichinosis. The authors provide the results of 3.5-year immunological studies of the patients with trichinosis and convalescents, infection-risk and healthy individuals; those of autopsies of the corpses of those who died from accidental causes unassociated with trichinosis, as well as examinations of domestic, synanthropic, and wild animals. The findings indicate that there is a focus of trichinosis with the low level of endemia in the Krymsky District of the Krasnodar Territory.


Health Care Professionals' Confidence and Preferences for Diagnostic Assays for SARS-CoV-2: A Global Study.
Background: The COVID-19 pandemic has led to an urgent requirement for novel diagnostic tests that determine infection with SARS-CoV-2 and the development of an immune response against it. The perspective of end users on the characteristics and clinical use of these assays has not been previously considered. Methods: We surveyed 17,186 health care professions (HCPs) in 29 countries to gauge opinion on the design, use, diagnostic impact and diagnostic accuracy of COVID-19 tests. Results were correlated with national statistics on the burden of disease and testing in individual countries. Results: HCPs overwhelmingly recognized the importance of COVID-19 tests but 37.1% were unsure of the appropriate timing of investigations relative to disease symptoms. Confidence in the diagnostic accuracy of assays varied inversely with COVID-19-related mortality in individual countries but had no relationship with the total number of tests performed. There was global consensus that the most important impact of positive antigen and antibody testing was confidence in returning to work following recovery. Saliva was the preferred sampling fluid for COVID-19 diagnostic tests in all groups surveyed. Conclusions: HCP input can ensure novel assays are fit for purpose in varied global health care settings, but HCPs may require support to effectively use novel diagnostics thus minimizing waste when supplies are limited.


Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.
Equilibrium dialysis (ED) is one of the most frequently used approaches to investigate drug binding, where the major drawbacks are the time to reach equilibrium (varying between 6 and 24 h), a long assay preparation time and complexity of automation. A rapid equilibrium dialysis (RED) device has recently become commercially available (Pierce Biotechnology, ThermoFisher Scientific, Waltham, MA) offering the potential for reduced preparation and equilibration times. The RED device comprises a Teflon base plate which holds up to 48 disposable dialysis cells. Each dialysis insert is made up of two side-by-side chambers separated by a vertical cylinder of dialysis membrane with a high membrane surface area-to-volume ratio. An independent validation of the RED approach for the measurement of human plasma protein binding (PPB) was carried out as a comparative analysis with standard ED evaluating equilibration time, assay reproducibility and accuracy and ease of use. Using a diverse set of 18 commercially available drugs spanning a range of physicochemical properties we have shown this to be a robust and accurate methodology, with a shorter preparation and dialysis time, capable of being automated as a high-throughput assay for the determination of PPB.


The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC1 enhances it. ABC1 expression is induced by cholesterol loading and cAMP treatment and is reduced upon subsequent cholesterol removal by apolipoproteins. The protein is incorporated into the plasma membrane in proportion to its level of expression. Different mutations were detected in the ABC1 gene of 3 unrelated patients. Thus, ABC1 has the properties of a key protein in the cellular lipid removal pathway, as emphasized by the consequences of its defect in patients with Tangier disease.


Inherited cardiac diseases, pluripotent stem cells, and genome editing combined-the past, present, and future.
Research on mechanisms underlying monogenic cardiac diseases such as primary arrhythmias and cardiomyopathies has until recently been hampered by inherent limitations of heterologous cell systems, where mutant genes are expressed in noncardiac cells, and physiological differences between humans and experimental animals. Human-induced pluripotent stem cells (hiPSCs) have proven to be a game changer by providing new opportunities for studying the disease in the specific cell type affected, namely the cardiomyocyte. hiPSCs are particularly valuable because not only can they be differentiated into unlimited numbers of these cells, but they also genetically match the individual from whom they were derived. The decade following their discovery showed the potential of hiPSCs for advancing our understanding of cardiovascular diseases, with key pathophysiological features of the patient being reflected in their corresponding hiPSC-derived cardiomyocytes (the past). Now, recent advances in genome editing for repairing or introducing genetic mutations efficiently have enabled the disease etiology and pathogenesis of a particular genotype to be investigated (the present). Finally, we are beginning to witness the promise of hiPSC in personalized therapies for individual patients, as well as their application in identifying genetic variants responsible for or modifying the disease phenotype (the future). In this review, we discuss how hiPSCs could contribute to improving the diagnosis, prognosis, and treatment of an individual with a suspected genetic cardiac disease, thereby developing better risk stratification and clinical management strategies for these potentially lethal but treatable disorders.


Impact of Spotter Sex on One Repetition Maximum Bench Press Performance.
Nickerson, BS, Salinas, G, Garza, JM, Cho, S, and Snarr, RL. Impact of spotter sex on one repetition maximum bench press performance. J Strength Cond Res 35(9): 2397-2400, 2021-Resistance exercise is popular because of favorable health outcomes associated with increased muscular fitness. For these reasons, 1 repetition maximum (1RM), mean velocity (MV), and peak power (PP) are of interest during the bench press. However, research has yet to evaluate whether spotter sex impacts bench press performance. Therefore, the purpose of this study was to determine the impact of spotter sex on bench press performance during a 1RM testing protocol. Twenty resistance-trained individuals (10 men and 10 women) visited the laboratory on 2 separate occasions. Estimated 1RM was self-reported by subjects before the 1RM protocol. During their visits, subjects had their 1RM (kg), MV (m·s-1), and PP (W) determined on a bench press 1RM protocol while using a male or female spotter. Deception was used by telling subjects the intent of the study was to determine the reliability of a linear position transducer for measuring MV and PP during the 1RM trials. The main findings revealed that measured 1RM values for male weight lifters were significantly higher than estimated 1RM values when using both a male (p = 0.01) and female spotter (p < 0.01). In addition, results revealed MV and PP were significantly higher for the 1RM trials when male weight lifters had a male spotter (both p < 0.01). Alternatively, there were no significant differences in estimated vs. measured 1RM values for women as well as no effect of spotter sex on bench press strength (all p > 0.05). Practitioners should note that sex of a spotter does not seem to impact measured 1RM. However, notable influences may be observed within MV and PP.


A Mouse Model of Vascularized Skin Transplantation.
Allogeneic skin tissues are highly antigenic and induce intensive immune rejection after composite tissue allotransplantation. Mouse models have advantages in mechanistic studies of immune rejection. However, due to technical challenge in vascular anastomosis with suture technique, mouse vascularized skin allotransplantation models are not widely used in studies of immune rejection. Therefore, the authors propose vascular anastomosis through cuff technique during allotransplantation of mouse donor free groin skin flaps to either recipient inguinal or cervical site. Free groin skin flaps from BALB/c or C57BL/6 donor mice were transplanted to the groin (inguinal vascularized skin transplantation [IVST]) or to the neck of recipient sites (cervical vascularized skin transplantation [CVST]) of C57BL/6 mice. A nonsuture cuff technique was utilized to anastomose the donor vessels with either femoral vessels in IVST recipients or common carotid arteries and external jugular veins in CVST mice. Immunosuppressant drugs were used in the allogeneic skin group. The overall success rate was higher in the CVST (88.5%) when compared with the IVST (78.9%). Total operation time in CVST mice lasted 96 minutes (95% confidence interval, 92-101 minutes) that was shorter than that for IVST mice (136 minutes, 95% confidence interval, 127-176 minutes; P < 0.01). Complications, such as hindlimb necrosis and self-mutilation, were observed in IVST mice. Rapamycin (3 mg/kg, daily) significantly prolonged vascularized skin allografts survival with median survival time of 80 days. All syngeneic grafts survived for more than 80 days. We developed a novel mouse vascularized skin transplantation model that is feasible for the study of clinically relevant skin rejection and tolerance.


A Revised Fibrinogen Cutoff Value in the Chinese Disseminated Intravascular Coagulation Scoring System May Provide a Better Prognostic Value for Hematological Malignancies.
To retrospectively validate the prognostic value of the latest Chinese disseminated intravascular coagulation (DIC) scoring system (CDSS) in hematological malignancies, 260 patients with confirmed hematological malignancies and suspected DIC in West China Hospital between 2011 and 2015 were included in this study. We evaluated via univariate and multivariate analyses the diagnostic biomarkers, and the cutoff levels used in the CDSS, except those for fibrinogen, were found to be valid. In subgroup analyses, the value of fibrinogen was found to be mainly unfit for the acute promyelocytic leukemia group. Forty-six patients (17.7%) had elevated fibrinogen levels (>4 g/L) and tended to have a poor prognosis, and thus we redetermined the cutoff value of fibrinogen (<1 g/L or >4 g/L was defined as abnormal). As a result, all of the markers used in the CDSS had prognostic value (including for the promyelocytic leukemia group); meanwhile, this modification also resulted in a larger area under the receiver operating characteristic curve compared to the CDSS and the International Society on Thrombosis and Haemostasis score. We believe that, with regard to prognosis prediction, this cutoff value modification for fibrinogen is preferable for DIC patients with a tendency toward severe hypofibrinogenemia. However, a multicenter, prospective study is needed to validate this possibility.


Neurocognitive status is associated with all-cause mortality among psychiatric, high-risk liver transplant candidates and recipients.
Judicious selection of potential liver transplant candidates and close monitoring of progress are essential to successful outcomes. Pretransplant psychosocial evaluations are the norm, but the relationship between psychosocial (and neurocognitive status) and longer term medical outcomes is understudied. This exploratory study sought to examine the relationship between objective measures of pretransplant psychosocial and neurocognitive status and service utilization, transplant status, and all-cause mortality. This retrospective chart review examined outcomes among 108 psychiatric, high-risk liver transplant candidates up to four years following initial evaluation. Predictor variables of outcomes included demographic, medical, neurocognitive, psychological, and mental health treatment variables. Transplant status and neurocognitive functioning were independently associated with all-cause mortality. None of the other variables were associated with outcomes. Better neurocognitive functioning in high-risk liver transplant candidates may allow for greater involvement in medical care and/or compliance with treatment recommendations. More aggressive assessment and management of neurocognitive dysfunction may improve outcomes. Objective measures identified significant psychopathology typical of liver transplant candidates but were not associated with outcomes; engagement in specialized mental health care may have attenuated this relationship. Further study is needed to better understand the relationship between psychosocial functioning and outcomes.


Several synthetic progestins with different potencies adversely affect reproduction of fish.
Synthetic progestins are widely used as a component in both contraceptives and in hormone replacement therapy (HRT), both on their own and in combination with EE2. Their presence in the environment is now established in wastewater effluent and river water and this has led to concerns regarding their potential effects on aquatic organisms living in these waters. We carried out in vivo experiments to determine the potencies of four different synthetic progestins on the reproductive capabilities of the fathead minnow (Pimephales promelas). We then performed a series of in vitro assays to try and determine the reason for the effects seen in the in vivo experiments. In the first experiment, fathead minnow exposed to a single concentration of 100 ng/L of either Levonorgestrel or Gestodene stopped spawning almost completely. The same nominal concentration of Desogestrel and Drospirenone did not affect reproduction (21 d NOECs of 100 ng/L). The second experiment investigated two progestins of different potency: Gestodene at 1, 10, and 100 ng/L and Desogestrel at 100 ng/L, 1 μg/L, and 10 μg/L. Gestodene concentrations as low as 1 ng/L had significant effects on reproduction over 21 d, whereas concentrations of Desogestrel at or above 1 μg/L were required to significantly reduce egg production. The synthetic progestins also masculinized the female fish in a concentration-dependent manner. Results from yeast-based in vitro assays demonstrated that the progestins are all strongly androgenic, thereby explaining the masculinization effects. The results strongly suggest that synthetic progestins merit serious consideration as environmental pollutants.


Effects of immunization against bone morphogenetic protein 15 and growth differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes.
Immunization of ewes against growth differentiation factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15) can lead to an increased ovulation rate; however, it is not known whether normal pregnancies occur following such treatments. The aims of the present study were to determine the effects of a short-term immunization regimen against BMP15 and GDF9 on ovulation rate, fertilization of released oocytes, the ability of fertilized oocytes to undergo normal fetal development, and the ability of immunized ewes to carry a pregnancy to term. Ewes were given a primary and booster immunization against keyhole limpet hemocyanin (KLH; control, n = 50), a GDF9-specific peptide conjugated to KLH (GDF9, n = 30), or a BMP15-specific peptide conjugated to KLH (BMP15, n = 30). The estrous cycles of all ewes were synchronized, and ewes were joined with fertile rams approximately 14 days after the booster immunization. The number of corpora lutea was determined by laparoscopy 3-4 days following mating. Subsequently, about one-half of the ewes in each group underwent an embryo transfer procedure 4-6 days following mating, with the embryos being transferred to synchronized, nonimmunized recipients. The remaining ewes were allowed to carry their pregnancies to term. Short-term immunization against either BMP15 or GDF9 peptides resulted in an increase in ovulation rate with no apparent detrimental affects on fertilization of released oocytes, the ability of fertilized oocytes to undergo normal fetal development, or the ability of the immunized ewes to carry a pregnancy to term. Therefore, regulation of BMP15, GDF9, or both is potentially a new technique to enhance fecundity in some mammals.


Improving Patient Care Using the Johnson-Neyman Analysis of Heterogeneity of Treatment Effects According to Individuals' Baseline Characteristics.
Because each patient's baseline (pre-treatment) characteristics differ (e.g., age, sex, socioeconomic status, ethnicity/race, biomarkers), treatments do not work the same for every patient-some can even cause detrimental effects. To improve patient care, it is critical to identify such heterogeneity of treatment effects. But the standard analytic approach dichotomizes baseline characteristics (low vs. high) which often leads to a loss of critical patient-care information and power to detect heterogeneity, as the results may depend strongly on the cut-points chosen. A more powerful analytic approach is to analyze baseline characteristics (i.e., covariates) measured on a continuous scale that retains all of the information available for the covariate. In this article, we show how the Johnson-Neyman (J-N) method can be used to identify the prognostic and predictive value of baseline covariates measured on a continuous scale - findings that often cannot be determined using the traditional dichotomized approach. As an example, we used the J-N method to explore treatment effects for varying levels of the biomarker salivary mutans streptococci (MS) in a randomized clinical prevention trial comparing fluoride varnish with no fluoride varnish for 376 initially caries-free high-risk children, all of whom received oral health counseling. The J-N analysis showed that children with higher baseline MS values who were randomized to receive fluoride varnish had the poorest dental caries prognosis and may have benefitted most from the preventive agent. Such methods are likely to be an important tool in the field of personalized oral health care.


Keloids: Fundamental principles and prospects (Review).
Wound healing is a very complex process of interactions between different cells, growth factors, blood elements and extracellular matrix. Keloids represent one of the possible complications in the fundamental process of cutaneous wound repair. Despite all efforts, keloids remain a therapeutic challenge since no treatment is as yet considered 100% effective. Growth factors, discovered in the late 1970s, have been shown to influence dermal regeneration. However, the exogenous application of growth factors to chronic wounds has not proven to be effective in healing them. Additionally, genetic analysis has not revealed any single gene that might cause keloids; as such, classic gene therapy is not a feasible option for the treatment of keloids. A new approach is so-called somatic gene therapy. This review provides an overview of the fundamentals of wound healing and of keloids, and presents new possibilities that may improve cutaneous wound repair.


[Indices of lipid peroxidation and antioxidant defense system and prostanoid level in patients with uterine cancer].
The state of peroxydal oxidation of lipids, system of antioxidant defense and content of prostanoids in patients with cancer of the corpus uteri were investigated. Syndrome of endogenous intoxication with lowering of antioxidant potential and dysbalance of cyclic nucleotides and prostaglandines was established. The severity of above-cited disorders increased significantly after operation and during conduction of radiotherapy. This demanded administration of antioxidant and detoxicational therapy in complex of preoperative preparation.


Role of copper efflux in pneumococcal pathogenesis and resistance to macrophage-mediated immune clearance.
In bacteria, the intracellular levels of metals are mediated by tightly controlled acquisition and efflux systems. This is particularly true of copper, a trace element that is universally toxic in excess. During infection, the toxic properties of copper are exploited by the mammalian host to facilitate bacterial clearance. To better understand the role of copper during infection, we characterized the contribution of the cop operon to copper homeostasis and virulence in Streptococcus pneumoniae. Deletion of either the exporter, encoded by copA, or the chaperone, encoded by cupA, led to hypersensitivity to copper stress. We further demonstrated that loss of the copper exporter encoded by copA led to decreased virulence in pulmonary, intraperitoneal, and intravenous models of infection. Deletion of copA resulted in enhanced macrophage-mediated bacterial clearance in vitro. The attenuation phenotype of the copA mutant in the lung was found to be dependent on pulmonary macrophages, underscoring the importance of copper efflux in evading immune defenses. Overall, these data provide insight into the role of the cop operon in pneumococcal pathogenesis.


Use of Isokinetic Dynamometry To Assess Muscle Function In Burned Patients Is A Reliable Tool To Assist Progressive Resistance Exercise Prescription.
Isokinetic dynamometry is used during exercise testing and rehabilitation to obtain a quantitative strength measurement on which progressive strength training programs can be based. This study assesses the test-retest reliability of isokinetic leg function in the knee flexors and extensors at 150°/s in children and young adults with severe burns to be used for rehabilitation exercise program prescription. In 39 severely burned patients (49 ± 14% total body surface area burn [TBSA], mean ± SD; 34 ± 21% TBSA 3rd degree; 14 ± 5 years, 153.3 ± 16.5 cm height; 53.8 ± 17.9 kg) knee flexion/extension isokinetic dynamometry at 150°/s was performed on each patient's dominant leg in two sessions. The patient was acquainted with the test and performed 1 set of 10 repetitions at 150°/s. A second session of 1 set of 10 repetitions at 150°/ was performed within 24 h of the first. Muscle function outcomes were knee flexion/extension peak torque, average peak torque, and average power. One-sample paired t tests were performed for all muscle function outcomes; intraclass correlation coefficients and r2 values with session two as a function of session one were calculated. Sessions did not differ significantly in knee extension or flexion for any muscle function outcome or the hamstrings to quadriceps ratio. All intraclass correlation coefficients were >0.89 and r2 > 0.79. Test-retest isokinetic dynamometry functional measurements in the knee flexors and extensors at 150°/s are reliable in the burn population and may aid resistance rehabilitation program prescriptions.


Somatic mRNA turnover mutants implicate tristetraprolin in the interleukin-3 mRNA degradation pathway.
Control of mRNA stability is critical for expression of short-lived transcripts from cytokines and proto-oncogenes. Regulation involves an AU-rich element (ARE) in the 3' untranslated region (3'UTR) and cognate trans-acting factors thought to promote either degradation or stabilization of the mRNA. In this study we present a novel approach using somatic cell genetics designed to identify regulators of interleukin-3 (IL-3) mRNA turnover. Mutant cell lines were generated from diploid HT1080 cells transfected with a reporter construct containing green fluorescent protein (GFP) linked to the IL-3 3'UTR. GFP was expressed at low levels due to rapid decay of the mRNA. Following chemical mutagenesis and selection of GFP-overexpressing cells, we could isolate three mutant clones (slowA, slowB, and slowC) with a specific, trans-acting defect in IL-3 mRNA degradation, while the stability of IL-2 and tumor necrosis factor alpha reporter transcripts was not affected. Somatic cell fusion experiments revealed that the mutants are genetically recessive and form two complementation groups. Expression of the tristetraprolin gene in both groups led to reversion of the mutant phenotype, thereby linking this gene to the IL-3 mRNA degradation pathway. The genetic approach described here should allow identification of the defective functions by gene transfer and is also applicable to the study of other mRNA turnover pathways.


Self-reported and clinically evident gingival bleeding and impact on oral health-related quality of life in young adolescents: a comparative study.
Very little is known about how self-reported gingival bleeding affects the oral health-related quality of life in adolescents compared with clinically evident bleeding. This study aimed to compare the impact of self-reported gingival bleeding and clinically evident gingival bleeding on the oral health-related quality of life in young adolescents. This was a cross-sectional study involving 976 students (aged 10-14 years) in randomly selected primary schools in Ibadan. Data were obtained by oral examination and completion of the Child Oral Impact on Daily Performance Questionnaire. Data were analysed with SPSS version 24. The Mann Whitney U test was used to determine the association between gingival bleeding and the quality of life. The mean age of the participants was 11.4±1.3 years. Almost half (48.3%) of the participants reported gingival bleeding during tooth cleaning while the gingiva of 534 (54.7%) participants bled on examination. Pupils with self-reported bleeding suffered a significantly greater impact on their overall quality of life than those without self-reported bleeding (mean ranks: 528.1 vs. 451.6, P<0.001). For pupils with self-reported bleeding, there were higher impacts on all domains relating to quality of life than those who did not report bleeding (eating: mean ranks=521.0 vs. 458.2; speaking: 502.2 vs. 475.8; teeth cleaning: 522.7 vs. 456.7; sleeping: 497.7 vs. 456.7; showing teeth/smiling: 503.4 vs. 474.6; emotional stability: 501.1 vs. 476.8; school work: 492.4 vs. 484.9, and enjoying contact with other children: 494.0 vs. 483.4). There was no statistically significant association between clinically evident bleeding and impacts on the quality of life (P=0.272). Almost half of the students reported gingival bleeding while cleaning their teeth and over 50% experienced gingival bleeding on probing. Those with self-reporting of gingival bleeding had greater impacts on oral health-related quality of life compared with those with clinically evident bleeding.


Food Liking Enhances the Plasma Response of 2-Arachidonoylglycerol and of Pancreatic Polypeptide upon Modified Sham Feeding in Humans.
Food palatability increases food intake and may lead to overeating. The mechanisms behind this observation are still largely unknown. The aims of this study were the following: 1) to elucidate the plasma responses of endocannabinoids, N-acylethanolamines, and gastrointestinal peptides to a palatable (sweet), unpalatable (bitter), and sensory-acceptable (tasteless control) food, and 2) to verify whether some of these bioactive compounds can serve as plasma biomarkers of food liking in humans. Three puddings providing 60 kcal (35% from proteins, 62% from carbohydrates, and 3% from fats) but with different taste were developed. Twenty healthy subjects (11 women and 9 men; mean age 28 y and BMI 22.7 kg/m(2)), selected because they liked the puddings in the order sweet > control > bitter, participated in a randomized crossover study based on a modified sham feeding (MSF) protocol. Blood samples at baseline and every 5 min up to 20 min after the MSF were analyzed for gastrointestinal peptides, endocannabinoids, and N-acylethanolamines. Thirty minutes after the MSF, energy intake at an ad libitum breakfast was measured. After the MSF, no response was observed in 7 of 9 gastrointestinal peptides measured. The plasma ghrelin concentration at 20 min after the sweet and bitter puddings was 25% lower than after the control pudding (P = 0.04), and the pancreatic polypeptide response after the sweet pudding was 23% greater than after the bitter pudding (P = 0.02). The plasma response of 2-arachidonoylglycerol after the sweet pudding was 37% and 15% higher than after the bitter (P < 0.001) and control (P = 0.03) puddings, respectively. Trends for greater responses of anandamide (P = 0.06), linoleoylethanolamide (P = 0.07), palmitoylethanolamide (P = 0.06), and oleoylethanolamide (P = 0.09) were found after the sweet pudding than after the bitter pudding. No differences in subsequent energy intake were recorded. The data demonstrated that food palatability influenced some plasma endocannabinoid and N-acylethanolamine concentrations during the cephalic phase response and indicated that 2-arachidonoylglycerol and pancreatic polypeptide can be used as biomarkers of food liking in humans.


Complexes of Cu-Polysaccharide of a Marine Red Microalga Produce Spikes with Antimicrobial Activity.
Metal-polysaccharides have recently raised significant interest due to their multifunctional bioactivities. The antimicrobial activity of a complex of Cu2O with the sulfated polysaccharide (PS) of the marine red microalga Porphyridium sp. was previously attributed to spikes formed on the complex surface (roughness). This hypothesis was further examined here using other Cu-PS complexes (i.e., monovalent-Cu2O, CuCl and divalent-CuO, CuCl2). The nanostructure parameters of the monovalent complexes, namely, longer spikes (1000 nm) and greater density (2000-5000 spikes/µm2) were found to be related to the superior inhibition of microbial growth and viability and biofilm formation. When Escherichia coli TV1061, used as a bioluminescent test organism, was exposed to the monovalent Cu-PS complexes, enhanced bioluminescence accumulation was observed, probably due to membrane perforation by the spikes on the surface of the complexes and consequent cytoplasmic leakage. In addition, differences were found in the surface chemistry of the monovalent and divalent Cu-PS complexes, with the monovalent Cu-PS complexes exhibiting greater stability (ζ-potential, FTIR spectra, and leaching out), which could be related to spike formation. This study thus supports our hypothesis that the spikes protruding from the monovalent Cu-PS surfaces, as characterized by their aspect ratio, are responsible for the antimicrobial and antibiofilm activities of the complexes.


Association of matrix metalloproteinase gene polymorphisms with refractive error in Amish and Ashkenazi families.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in scleral extracellular matrix remodeling and have shown differential expression in experimental myopia. The genetic association of refractive error and polymorphisms in MMP and TIMP genes in Old Order Amish (AMISH) and Ashkenazi Jewish (ASHK) families was investigated. Individuals from 55 AMISH and 63 ASHK families participated in the study. Ascertainment was designed to enrich the families for myopia; the mean spherical equivalent (MSE) refractive error (SD) was -1.61 (2.72) D in the AMISH, and -3.56 (3.32) D in the ASHK. One hundred forty-six common haplotype tagging SNPs covering 14 MMP and 4 TIMP genes were genotyped in 358 AMISH and 535 ASHK participants. Association analyses of MSE and the spherical component of refraction (SPH) were performed separately for the AMISH and the ASHK. Bonferroni-corrected significance thresholds and local false discovery rates were used to account for multiple testing. After they were filtered for quality-control, 127 SNPs were included in the analyses. No polymorphisms showed statistically significant association to refraction in the ASHK (minimum P = 0.0132). In AMISH, two SNPs showed evidence of association with refractive phenotypes: rs1939008 (P = 0.00016 for SPH); and rs9928731 (P = 0.00026 for SPH). These markers were each estimated to explain <5% of the variance of SPH in the AMISH sample. Statistically significant genetic associations of ocular refraction to polymorphisms near MMP1 and within MMP2 were identified in the AMISH but not among the ASHK families. The results suggest that the MMP1 and MMP2 genes are involved in refractive variation in the AMISH. Genetic and/or environmental heterogeneity most likely contribute to differences in association results between ethnic groups.


DNA methylation profiling of a cnidarian-algal symbiosis using nanopore sequencing.
Symbiosis with protists is common among cnidarians such as corals and sea anemones and is associated with homeostatic and phenotypic changes in the host that could have epigenetic underpinnings, such as methylation of CpG dinucleotides. We leveraged the sensitivity to base modifications of nanopore sequencing to probe the effect of symbiosis with the chlorophyte Elliptochloris marina on methylation in the sea anemone Anthopleura elegantissima. We first validated the approach by comparison of nanopore-derived methylation levels with CpG depletion analysis of a published transcriptome, finding that high methylation levels are associated with CpG depletion as expected. Next, using reads generated exclusively from aposymbiotic anemones, a largely complete draft genome comprising 243 Mb was assembled. Reads from aposymbiotic and symbiotic sea anemones were then mapped to this genome and assessed for methylation using the program Nanopolish, which detects signal disruptions from base modifications as they pass through the nanopore. Based on assessment of 452,841 CpGs for which there was adequate read coverage (approximately 8% of the CpGs in the genome), symbiosis with E. marina was, surprisingly, associated with only subtle changes in the host methylome. However, we did identify one extended genomic region with consistently higher methylation among symbiotic individuals. The region was associated with a DNA polymerase zeta that is noted for its role in translesion synthesis, which opens interesting questions about the biology of this symbiosis. Our study highlights the power and relative simplicity of nanopore sequencing for studies of nucleic acid base modifications in non-model species.


Effectiveness of multicomponent treatment in patients with fibromyalgia: protocol for a systematic review and meta-analysis.
The purpose of this protocol is to provide a new systematic review with meta-analysis using the current methodology to compare the effectiveness of multicomponent treatment versus other interventions for patients with fibromyalgia. This protocol conforms to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and the recommendations of the Cochrane Collaboration Handbook. An electronic search will be conducted in MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL, LILACS, CINAHL, and PEDro, from inception until April 2022. There will be no language restrictions. The Cochrane Collaboration tool for assessing the risk of bias (RoB2) will be used. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale will be used to evaluate the strength of the evidence. The Hartung-Knapp-Sidik-Jonkman random effects or Mantel-Haenszel fixed effects methods will be used, depending on the heterogeneity, to compute a pooled estimate of the mean difference (MD) or standardized mean difference (SMD) and respective 95% confidence intervals for clinical outcomes. This systematic review will synthesize evidence on the effectiveness of multicomponent treatment in patients with fibromyalgia and could add important evidence in the treatment of FM to improve clinical practice and decision-making/actions in this field. This new systematic review will try to show the effects of multicomponent treatment by type (endurance, resistance, stretching, or mind-body exercises [pilates or taichi]) and intensity (light, moderate, moderate-to-vigorous, vigorous) of exercise in patients with FM. The results will be disseminated by publication in a peer-reviewed journal. Ethics approval will not be needed because the data used for this systematic review will be obtained from individual trials and there will be no concerns about privacy. However, if we identify ethical issues during the development of the systematic review, these findings will be reported in the discussion of the study. PROSPERO CRD42020142082.


A block copolymer-templated construction approach for the creation of nano-patterned polyelectrolyte multilayers and nanoscale objects.
A block copolymer-based assembly approach for the creation of nano-patterned polyelectrolyte multilayers over cm2-scale areas is presented. Up to 5 bi-layers were selectively assembled on top of specific nano-domains featuring different morphologies. The successful isolation of nanoscale objects corresponding in shape to the template features is also demonstrated. This methodology is applicable to different types of polyelectrolytes, and opens up a new dimension for layer-by-layer construction.


Dynamics of tumor growth and cellular adaptation after inoculation into nude mice of varying numbers of transformed 3T3 cells and of readaptation to culture of the tumor cells.
Decimal dilutions containing 5 X 10(5) to 5 X 10(1) cells were inoculated s.c. into nude mice and the course of tumor development was recorded. The highest concentration of cells produced rapidly growing poorly differentiated sarcomas within 2-3 weeks of their inoculation. Upon explantation the resultant tumors yielded cells which multiplied on plastic almost as rapidly as did their progenitors used to initiate the tumors, and had as high a colony forming efficiency in agar as long as tryptose phosphate broth was omitted from the agar medium. Tumors initiated by the lower concentrations of cells were disproportionately delayed in their appearance and tended to increase in size at a low rate. At least one tumor regressed and one which apparently regressed appeared again at a later time. These changes are characteristically described under the rubric of tumor regression. Host reactive cells such as neutrophils, eosinophils, macrophages, and fibroblasts were observed in some tumors. One of the tumors was a low grade hemangiosarcoma, another a well-differentiated fibrosarcoma, and the rest poorly differentiated sarcomas. Cells from two tumors initiated by 500 and 5000 cells multiplied slowly in early passages in culture, particularly when seeded at low densities at which they appeared to sustain cumulative damage even when multiplying. In later passages, the "low dose" tumor cells gained the capacity to multiply in culture after seeding at low densities, but it took up to 50 cell generations to reach this capacity. The loss of growth capacity on plastic of cells from the low dose tumors and its subsequent restoration by passaging in culture may provide a quantitative method for analyzing the type of cellular change which underlies tumor progression.


[Morphological and histochemical effects of subthreshold laser therapy on the chorioretinal complex].
A variety of subthreshold laser methods that enable selective and precise treatment of chorioretinal microstructures, thus decreasing the risk of negative changes in retina and choriocapillaries, is used in current ophthalmological practice. This comparative pathomorphological and histochemical study allowed characterizing structural changes and functional activity of chorioretinal cells after application of different subthreshold laser technologies.


Analysis of the expression of terpene synthase genes in relation to aroma content in two aromatic Vitis vinifera varieties.
Grape (Vitis vinifera L.) flavour management in the vineyard requires knowledge of the derivation of individual flavour and aroma characteristics. Some of the most prevalent wine grape aroma constituents are terpenoids and this study represents a wide report about grape terpene synthase (TPS) gene transcript profiling in different tissues of two aromatic grapevine varieties, particularly flowers and developing berries, correlated with the accumulation patterns of free aroma compounds. All investigated genes belonging to the TPS-a and TPS-b subfamilies reached the highest expression in accordance with the peak of accumulation of the respective compounds. In the TPS-g subfamily, only one of the genes characterised for linalool synthases showed major transcript abundance in ripening berries, whereas the only geraniol synthase had a peak of expression in green berries and at the beginning of ripening, when geraniol concentration started to increase and overcome the linalool concentration. The genes identified in this study as being mainly responsible for linalool and geraniol synthesis during berry development, and the phenological phases in which they are mostly expressed, should be of interest to viticulturists and wine makers to improve decision making along the chain of production.


Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.
To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Hospital based registry study. Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. 69,265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Of the 69,265 enrolled patients 34,800 (50.2%) received protective ventilation and 34,465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.


Implementing person-centred outcome measures in palliative care: An exploratory qualitative study using Normalisation Process Theory to understand processes and context.
Despite evidence demonstrating the utility of using Person-Centred Outcome Measures within palliative care settings, implementing them into routine practice is challenging. Most research has described barriers to, without explaining the causal mechanisms underpinning, implementation. Implementation theories explain how, why, and in which contexts specific relationships between barriers/enablers might improve implementation effectiveness but have rarely been used in palliative care outcomes research. To use Normalisation Process Theory to understand and explain the causal mechanisms that underpin successful implementation of Person-Centred Outcome Measures within palliative care. Exploratory qualitative study. Data collected through semi-structured interviews and analysed using a Framework approach. 63 healthcare professionals, across 11 specialist palliative care services, were purposefully sampled by role, experience, seniority, and settings (inpatient, outpatient/day therapy, home-based/community). Seven main themes were developed, representing the causal mechanisms and relationships underpinning successful implementation of outcome measures into routine practice. Themes were: Subjectivity of measures; Frequency and version of Integrated Palliative care Outcome Scale; Training, education, and peer support; Building and sustaining community engagement; Electronic system readiness; The art of communication; Reinforcing use through demonstrating value. Relationships influencing implementation resided at individual and organisational levels. Addressing these factors is key to driving the implementation of outcome measures into routine practice so that those using palliative care services can benefit from the systematic identification, management, and measurement of their symptoms and concerns. We provide key questions that are essential for those implementing and using outcome measures to consider in order to facilitate the integration of outcome measures into routine palliative care practice.


Elucidation of the relationships between H-bonding patterns and excited state dynamics in cyclovalone.
Cyclovalone is a synthetic curcumin derivative in which the keto-enolic system is replaced by a cyclohexanone ring. This modification of the chemical structure might in principle result in an excited state that is more stable than that of curcumin, which in turn should produce an enhanced phototoxicity. Indeed, although curcumin exhibits photosensitized antibacterial activity, this compound is characterized by very fast excited-state dynamics which limit its efficacy as a photosensitizer. In previous works we showed that the main non-radiative decay pathway of keto-enolic curcuminoids is through excited-state transfer of the enolic proton to the keto-oxygen. Another effective deactivation pathway involves an intermolecular charge transfer mechanism occurring at the phenyl rings, made possible by intramolecular H-bonding between the methoxy and the hydroxyl substituent. In this paper we present UV-Vis and IR absorption spectra data with the aim of elucidating the intramolecular charge distribution of this compound and its solvation patterns in different environments, with particular focus on solute-solvent H-bonding features. Moreover, we discuss steady state and time-resolved fluorescence data that aim at characterizing the excited-state dynamics of cyclovalone, and we compare its decay photophysics to that of curcumin. Finally, because during the characterization procedures we found evidence of very fast photodegradation of cyclovalone, its photostability in four organic solvents was studied by HPLC and the corresponding relative degradation rates were calculated.


Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo.
The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patient with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF and that in some cases, serum actually masked the effects of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF from human mononuclear cells demonstrated that both were active in their iron-saturated form.(ABSTRACT TRUNCATED AT 400 WORDS)


A study of P300-event related evoked potential in the patients of major depression.
Many studies involving various electrophysiological parameters have been conducted in psychiatric disorders like schizophrenia and dementia to assess their cognitive dysfunctions. Not much reports are available in major depression. The present study was conducted in 20 patients of major depression to evaluate their cognitive functions in terms of P300. P300 or P3 wave of auditory event related evoked potentials (ERPs) is usually seen around 300 msec of presenting of target stimulus, if the subject is responding to it. Auditory ERPs were recorded using the standard 'odd ball' paradigm. The latencies of various components of ERPs N1, N2, P1, P2, and P3 were recorded and compared with those of 20 normal age and sex matched controls. The latency of P300 was found to be significantly delayed in cases of major depression as compared to that of controls. Other waves were also delayed in cases of depression but the difference was not statistically significant. Our results suggest that P300 latency is longer in the patients of major depression disorders which could be due to constitutive altered 'cognitive neuronal pool' or a neurotransmitter/neuropeptide imbalance. Further studies involving larger populations are required to elucidate the diagnostic and predictive role of latency of P300 in the cases of depression.


Increased erythrocyte superoxide dismutase activities in beta 0-thalassaemia/haemoglobin E and in haemoglobin H diseases.
Erythrocyte superoxide dismutase activities were measured in 45 subjects, 15 each of beta 0-thalassaemia/haemoglobin (Hb) E disease, Hb H disease, and normal. The erythrocyte superoxide dismutase activities were significantly higher in the patients with beta 0-thalassaemia/Hb E and Hb H diseases than in the normal subjects. The increase of erythrocyte superoxide dismutase activities is most likely due to abnormalities specific to thalassaemic red cells rather than an increased number of younger red cells for reticulocytes and nucleated red blood cells did not affect the enzyme activity. Patients with beta 0-thalassaemia/Hb E disease with lower haemoglobin concentration had significantly higher superoxide dismutase activities. In all 45 subjects haemoglobin concentrations and superoxide dismutase activities were inversely correlated (r = -0.60 (p less than 0.001)). This indicates that the amounts of superoxide generated in the red cells may, at least partly, determine severity of red cell damage and thus severity of disease; the increased superoxide dismutase activity in thalassaemia is a response to superoxide generated in greater amounts because of accumulation of excessive globin chains and iron in the red cells. The superoxide dismutase activities in Hb H disease, an alpha-thalassaemic disease, were found to be strikingly increased, higher than in beta 0-thalassaemic disease or other conditions.


Continuous-Flow Left Ventricular Assist Device Therapy in Adults with Transposition of the Great Vessels.
An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.


Use of email and telephone prompts to increase self-monitoring in a Web-based intervention: randomized controlled trial.
Self-monitoring is a key behavior change mechanism associated with sustained health behavior change. Although Web-based interventions can offer user-friendly approaches for self-monitoring, engagement with these tools is suboptimal. Increased use could encourage, promote, and sustain behavior change. To determine whether email prompts or email plus telephone prompts increase self-monitoring of behaviors on a website created for a multiple cancer risk reduction program. We recruited and enrolled participants (N = 100) in a Web-based intervention during a primary care well visit at an urban primary care health center. The frequency of daily self-monitoring was tracked on the study website. Participants who tracked at least one behavior 3 or more times during week 1 were classified as meeting the tracking threshold and were assigned to the observation-only group (OO, n = 14). This group was followed but did not receive prompts. Participants who did not meet the threshold during week 1 were randomly assigned to one of 2 prompting conditions: automated assistance (AA, n = 36) or automated assistance + calls (AAC, n = 50). During prompting periods (weeks 2-3), participants in the AA and AAC conditions received daily automated emails that encouraged tracking and two tailored self-monitoring reports (end of week 2, end of week 3) that provided feedback on tracking frequency. Individuals in the AAC condition also received two technical assistance calls from trained study staff. Frequency of self-monitoring was tracked from week 2 through week 17. Self-monitoring rates increased in both intervention conditions during prompting and declined when prompting ceased. Over the 16 weeks of observation, there was a significant between-group difference in the percentage who met the self-monitoring threshold each week, with better maintenance in the AAC than in the AA condition (P < .001). Self-monitoring rates were greater in the OO group than in either the AA or AAC condition (P < .001). Prompting can increase self-monitoring rates. The decrease in self-monitoring after the promoting period suggests that additional reminder prompts would be useful. The use of technical assistance calls appeared to have a greater effect in promoting self-monitoring at a therapeutic threshold than email reminders and the tailored self-monitoring reports alone. ClinicalTrials.gov NCT01415492; http://clinicaltrials.gov/ct2/show/NCT01415492 (Archived by WebCite at http://www.webcitation.org/68LOXOMe2).


Chemistry and biology of biosynthetic Diels-Alder reactions.
Nature's repertoire of biosynthetic transformations has recently been recognized to include the Diels-Alder cycloaddition reaction. Evidence now exists that there are enzymes that mediate the Diels-Alder reaction in secondary metabolic biosynthetic pathways. 2002 marked the 100th anniversary of Alder's birth and 75 years since the discovery of the Diels-Alder reaction. It would appear that living systems discovered and made use of this ubiquitously useful ring-forming reaction eons ago for the construction of complex natural products. In this Review an overview is given of all of the known classes of natural products (polyketides, isoprenoids, phenylpropanoids, alkaloids) that have been speculated to arise by a biological Diels-Alder reaction.


Sentinel community Clostridium difficile infection (CDI) surveillance in Scotland, April 2013 to March 2014.
Surveillance of Clostridium difficile infection (CDI) in Scotland does not currently distinguish between CDI cases from hospitals and the community. Therefore, the incidence of CDI in the community is unknown, and the burden of disease and the relationship with the hospital/healthcare setting is not well understood. A one-year sentinel community surveillance programme was initiated in collaboration with five Scottish health boards in 2013 (representing 36% of all CDI cases reported in Scotland). Inclusion criteria were all cases aged ≥15 years with a CDI diagnosis in the community or within 48 h following admission to hospital. CDI cases were categorised according to definitions used by the European Centre for Disease Prevention and Control. 256 CDI cases met the inclusion criteria, of which 158 (62%) were community-associated cases (CA-CDI). This represented 26% of all cases reported during the surveillance period by the participating health boards (n = 614). The overall CA-CDI incidence rate was 9.9 per 100 000 population per year. CA-CDI cases were more likely to be female and younger, compared to hospital acquired cases (HA-CDI). The total proportion of cases that had onset in the community was 27%. Ribotypes 015, 002, 078 and 005 were the most common types isolated from both CA-CDI and HA-CDI cases. There were no statistically significant differences between the proportion of types that were either CA-CDI or HA-CDI. Of the CA-CDI cases, 37% had not received antibiotics in the 12 weeks preceding CDI diagnosis, 4% were resident in care homes, and the case-fatality rate for CA-CDI cases was 5.6% (with a 30-day mortality rate for CA-CDI of 0.44 per 100 000 population per year). This study has shown that a substantial proportion of CDI cases reported in Scotland are community associated and that there are close links between the community and healthcare settings. It is therefore essential to monitor the trends in CDI in the community at a national level. The study also provides evidence for the need to examine the feasibility for development of interventions to reduce the burden in the community in addition to hospitals.


Effect of protein overfeeding on energy expenditure measured in a metabolic chamber.
Energy expenditure (EE) increases with overfeeding, but it is unclear how rapidly this is related to changes in body composition, increased body weight, or diet. The objective was to quantify the effects of excess energy from fat or protein on energy expenditure of men and women living in a metabolic chamber. We conducted a randomized controlled trial in 25 participants who ate ∼40% excess energy for 56 d from 5%, 15%, or 25% protein diets. Twenty-four-hour EE (24EE) and sleeping EE (SleepEE) were measured on days 1, 14, and 56 of overfeeding and on day 57 while consuming the baseline diet (usually day 57). Metabolic and molecular markers of muscle metabolism were measured in skeletal muscle biopsy specimens. In the low-protein diet group whose excess energy was fat, the 24EE and SleepEE did not increase during the first day of overfeeding. When extra energy contained protein, both 24EE and SleepEE increased in relation to protein intake (r = 0.50, P = 0.02). The 24EE over 8 wk in all 3 groups was correlated with protein intake (r = 0.60, P = 0.004) but not energy intake (r = 0.16; P = 0.70). SleepEE was unchanged by overfeeding in the low-protein diet group, and baseline surface area predicted increased 24EE in this group. Protein and fat oxidation were reciprocally related during overfeeding. Observed 24EE was higher than predicted on days 1 (P ≤ 0.05), 14 (P = 0.0001), and 56 (P = 0.0007). There was no relation between change in fat mass and change in EE. Excess energy, as fat, does not acutely increase 24EE, which rises slowly as body weight increases. Excess energy as protein acutely stimulates 24EE and SleepEE. The strongest relation with change in 24EE was the change in energy expenditure in tissue other than muscle or fat-free mass.


A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer.
Cisplatin-based combination therapy produces higher response rates and improved survival, in comparison to single-agent cisplatin in the treatment of cervical cancer. Cisplatin and paclitaxel (PT) requires a prolonged infusion and is less convenient and more toxic than the combination of carboplatin and paclitaxel (CT) leading to more widespread use of CT. The objective of this study was to compare response rate and survival in patients with cervical cancer treated with PT or CT. A retrospective search of databases at the University of Oklahoma, Washington University-Barnes Jewish Christian Hospitals, Johns Hopkins University, and University of Alabama at Birmingham identified patients with stage IVB, recurrent or persistent cervical cancer who were treated with PT or CT. A total of 62 patients were identified. 14 were treated with PT and 48 with CT. There were no statistical differences between the groups in terms of demographics, prior radiation therapy, or median number of cycles. There was a trend toward a larger number of patients in the CT arm having received prior cisplatin/radiation (p=0.07). Objective responses occurred in 29% of patients receiving PT vs. 53% of patients receiving CT. With a median follow-up of 9 months, survival was not different with a median survival of 14 and 11 months, respectively. In this retrospective evaluation, CT compares favorably with PT and demonstrates a superior overall response rate. Because of its ease of administration and improved toxicity profile, CT should be considered in the treatment of advanced, recurrent or progressive cervical cancer.


Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group.
To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas. CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology. The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections. CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.


Examining national and district-level trends in neonatal health in Peru through an equity lens: a success story driven by political will and societal advocacy.
Peru has impressively reduced its neonatal mortality rate (NMR). We aimed, for the period 2000-2013, to: (a) describe national and district NMR variations over time; (b) assess NMR trends by wealth quintile and place of residence; (c) describe evolution of mortality causes; (d) assess completeness of registered mortality; (e) assess coverage and equity of NMR-related interventions; and (f) explore underlying driving factors. We compared national NMR time trends from different sources. To describe NMR trends by wealth quintiles, place of residence and districts, we pooled data on births and deaths by calendar year for neonates born to women interviewed in multiple surveys. We disaggregated coverage of NMR-related interventions by wealth quintiles and place of residence. To identify success factors, we ran regression analyses and combined desk reviews with qualitative interviews and group discussions. NMR fell by 51 % from 2000 to 2013, second only to Brazil in Latin America. Reduction was higher in rural and poorest segments (52 and 58 %). District NMR change varied by source. Regarding cause-specific NMRs, prematurity decreased from 7.0 to 3.2 per 1,000 live births, intra-partum related events from 2.9 to 1.2, congenital abnormalities from 2.4 to 1.8, sepsis from 1.9 to 0.8, pneumonia from 0.9 to 0.4, and other conditions from 1.2 to 0.7. Under-registration of neonatal deaths decreased recently, more in districts with higher development index and lower rural population. Coverage of family planning, antenatal care and skilled birth attendance increased more in rural areas and in the poorest quintile. Regressions did not show consistent associations between mortality and predictors. During the study period social determinants improved substantially, and dramatic out-of-health-sector and health-sector changes occurred. Rural areas and the poorest quintile experienced greater NMR reduction. This progress was driven, within a context of economic growth and poverty reduction, by a combination of strong societal advocacy and political will, which translated into pro-poor implementation of evidence-based interventions with a rights-based approach. Although progress in Peru for reducing NMR has been remarkable, future challenges include closing remaining gaps for urban and rural populations and improving newborn health with qualified staff and intermediate- and intensive-level health facilities.


Induction of common patterns of polypeptide synthesis and phosphorylation by calcium and 12-O-tetradecanoylphorbol-13-acetate in mouse epidermal cell culture.
Terminal differentiation can be induced in cultured basal cells by either increasing the Ca2+ level in the medium from 0.05 to 1.4 mM or by exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). If Ca2+ and TPA act by a common mechanism, then a common pattern of protein synthesis and/or phosphorylation would be expected. Computer-assisted analysis of radioactively labeled polypeptides separated by two-dimensional-polyacrylamide gel electrophoresis was utilized to study protein synthesis and phosphorylation. Within 1 h of increasing the Ca2+ level in the medium, the synthesis of 57 polypeptides was altered by 2-fold or more. Similarly, exposure to TPA for 1 h affected the synthesis of 106 polypeptides. Sixteen polypeptides were affected by both Ca2+ and TPA; the synthesis of nine was increased and seven was decreased, with changes in the same direction for both effectors. By 4 h, the synthesis of 32 polypeptides was similarly modulated by both Ca2+ and TPA. Only one polypeptide which was increased at 1 h was still elevated at 4 h. These results suggest that a common dynamic program of protein synthesis, likely to be related to terminal keratinocyte differentiation, is induced by both Ca2+ and TPA. Overall phosphorylation of epidermal proteins was increased after 30 min of TPA treatment, but was not increased by Ca2+ at this time. Keratin polypeptides were heavily phosphorylated in low Ca2+ medium, but the level or pattern of phosphorylation of these proteins was not altered by either Ca2+ or TPA. Although phosphorylation of a minor polypeptide (pI 5.1/Mr 45,000) was increased 2-3-fold by both Ca2+ and TPA, most of the specific protein phosphorylation changes induced in keratinocytes by Ca2+ and TPA appear to be unique. Thus, if protein phosphorylation is an early signal for epidermal differentiation by each effector, only a single apparent common substrate is involved and multiple kinases are activated. Alternatively, substrate specificity of a single kinase may be differentially altered by each effector.


Combined effects of sous-vide cooking conditions on meat and sensory quality characteristics of chicken breast meat.
This study investigated the combined effects of cooking temperature and time on the meat and eating quality characteristics of the sous-vide chicken breast. For the control group, chicken breast samples were cooked in a convection oven until the internal temperature reached 71°C. Each sample for sous-vide cooking was vacuum packaged and then cooked under continuous thermocontrolled conditions in a water bath at 6 combinations of cooking temperature (60 and 70°C) and time (1, 2, and 3 h). Sous-vide cooked chicken meat at 60°C for 1 h (SV60-1h) showed lower cooking loss (6.58 vs. 26.5%, P < 0.05), Warner-Bratzler shear force (21.7 vs. 29.1 N, P < 0.05), and hardness (9.40 vs. 17.3 N, P < 0.05) than meat cooked by conventional oven. Similar to the objective tenderness parameters, cooked chicken meat from the SV60 treatments for all cooking times showed higher scores in all the tenderness attributes than the control group (P < 0.05). However, a higher flavor intensity was observed in the SV70-3h and control groups than in the SV60 treatments (P < 0.05). Owing to a lesser developed flavor in chicken meat from the SV60-1h treatment, the SV60-2h and 3h treatments were assigned a higher acceptability rating for overall impression (P < 0.05). Therefore, cooking temperature and time of sous-vide significantly influenced the physicochemical and palatability characteristics of chicken breast. In this study, the optimum conditions for the sous-vide chicken breast are to continuously cook at 60°C for 2 to 3 h to improve sensory quality characteristics without reducing the water-holding capacity.


A Structured Approach to Online Learning Design in Dental Education.
This article was migrated. The article was marked as recommended. The transition to online learning is an accepted and anticipated change across all higher education institutions. These changes have become even more relevant to healthcare education given the challenges posed by COVID19. This paper describes the application of the Cambridge Education Group Pedagogic Framework (2018) to online dental education, specifically the conversion of a face-to-face 'Transition to Clinical Practice' module in paediatric dentistry. The framework has a foundation in medical education and holds great value for clinical academics across all healthcare disciplines in the design and implementation of online teaching. This affords educators much needed structure and assistance in meeting the needs of our students in this era of online learning. The advantages and disadvantages are explored, illustrated by student feedback, following a pilot implementation at a Dental School in the United Kingdom.


Dirac dynamics in one-dimensional graphene-like plasmonic crystals: pseudo-spin, chirality, and diffraction anomaly.
We introduce a new class of plasmonic crystals possessing graphene-like internal symmetries and Dirac-type spectrum in k-space. We study dynamics of surface plasmon polaritons supported in the plasmonic crystals by employing the formalism of Dirac dynamics for relativistic quantum particles. Through an analogy with graphene, we introduce a concept of pseudo-spin and chirality to indicate built-in symmetry of the plasmonic crystals near Dirac point. The surface plasmon polaritons with different pseudo-spin states are shown to split in the crystals into two beams, analogous to spin Hall effect.


Polypoidal choroidal vasculopathy in a patient with angioid streaks treated by bevacizumab.
We report the association of polypoid choroidal vasculopathy (PVC) with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE) treated by intravitreal injection of bevacizumab. A 50-year-old patient, followed in dermatology for a PXE, who consulted for a consulted for a decreased vision in his right eye (RE) for a month. On examination, best corrected visual acuity (BCVA) was at 1/20 P14 in the RE and at 8/10 P2 in the left eye (LE). Fundus examination revealed AS in both eyes, large patches of exudate at the posterior pole with retinal hemorrhages in the RE. Fluorescein angiography (FA) showed constant hypofluorescence by mask effect due to exudates and macular early hyperfluorescence with late diffusion associated with small hyperfluorescent lesions in the RE. We suspected CNV type 2. Macular Spectral Domain optical coherence tomography (SD-OCT) showed significant retinal infiltration with pre-epithelial hyper-reflectivity bracing the diagnosis of type 2 CNV. In view of the importance of exudates and intra-retinal infiltration, we completed by indocyanine green angiography (ICGA) which showed hypercyanecent vascular dilations grouped in clusters of grapes relevant to an associated VPC. The patient received eight monthly intravitreal (IVT) injections of bevacizumab with good anatomical evolution. At 10 months, visual acuity was 1/10 with disappearance of exudates and retinal infiltration. Patients with AS should receive regular follow-up given the risk of CNV but also of VPC, especially in cases of PXE. Multimodal imaging is of great help and ICGA remains inescapable.


Mindfulness-Based Programs Improve Psychological Flexibility, Mental Health, Well-Being, and Time Management in Academics.
(1) Background: Occupational stress is high in academia, and is partly related to time pressure. Mindfulness-based programs are known to be effective in reducing stress and increasing well-being. Recent work suggested that these programs may also improve time management. This study tested the effects of a mindfulness-based program on academics' psychological flexibility, mental health, well-being, and time management. (2) Methods: The study was conducted in a French research department. Participants were offered to join a mindfulness-based program (n = 21) or to be on a wait-list control group (n = 22). Self-reported measures of psychological flexibility, mental health (stress, anxiety, and depression symptoms), well-being, and time use were collected before and after the eight week program. (3) Results: Results showed that psychological flexibility, mental health, well-being, and efficient time use significantly increased in the intervention group compared to the control condition. (4) Conclusions: The results suggested that the mindfulness-based programs were effective in improving adaptive functioning, well-being, and optimal time use in academia, thus underlining potential useful perspectives to help academics improve mental health and time management.


[Regulation of carbohydrate metabolism in patients with tumors of the sellar-diencephalic area before and after surgery].
Clinical and biochemical examination conducted in 40 patients with tumors of the sellar-diencephalic region before and after operation and in 8 healthy individuals revealed in the patients disorders of the function of the hypothalamus and alpha- and beta-cells of the pancreas in the presence of neurological and endocrine disorders. Radioimmunologic determination of insulin and glucagon in the blood disclosed activation of alpha- and beta-cells of the islets of Langerhans in patients with normal blood glucose content before surgery and inadequacy of the reaction of the pancreatic alpha- and beta-cells to the operation stress in patients with diminished or increased concentration of glucose in blood before surgery. Dysfunction of the hypothalamus and endocrine cells of the pancreas in tumors of the sellar-diencephalic region gives grounds for applying postoperative corrective therapy including preparations of insulin and glucagon in patients with progressive signs of a brain lesion.


An evaluation of the influence of substrate on the response of juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) in acute water exposures to ammonia.
Acute 96-h ammonia toxicity to three-month-old juvenile mussels (Lampsilis siliquoidea) was evaluated in four treatments (water-only, water-only with feeding, water and soil, and water and sand) using an exposure unit designed to maintain consistent pH and ammonia concentrations in overlying water and in pore water surrounding the substrates. Median effect concentrations (EC50s) for total ammonia nitrogen in the four treatments ranged from 5.6 to 7.7 mg/L and median lethal concentrations (LC50s) ranged from 7.0 to 11 mg/L at a mean pH of 8.4. Similar EC50s or LC50s with overlapping 95% confidence intervals among treatments indicated no influence of substrate on the response of mussels in acute exposures to ammonia.


The impact of Alzheimer disease genetics on expert and advanced gerontological nursing practice.
Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the United States, affecting as many as 4 million people. Extensive research is under way to identify environmental and genetic risk factors for this complex disease. Currently, four genes are associated with an increased risk for AD: the amyloid precursor protein gene on chromosome 21, the Presenilin I gene on chromosome 14, the Presenilin II gene on chromosome 1, and the apolipoprotein E gene on chromosome 19. Expert and advanced practice gerontological nurses are faced with new challenges as a result of these gene discoveries. Gerontological nurses should assess for relevant environmental and genetic risk factors; obtain comprehensive family health histories recorded as pedigrees; integrate genetic information into diagnosis, intervention, and evaluation strategies; initiate and coordinate referrals to genetic specialists; and provide ongoing emotional and decision-making support for patients and families experiencing AD.


Early increase of CSF sTREM2 in Alzheimer's disease is associated with tau related-neurodegeneration but not with amyloid-β pathology.
TREM2 is a transmembrane receptor that is predominantly expressed by microglia in the central nervous system. Rare variants in the TREM2 gene increase the risk for late-onset Alzheimer's disease (AD). Soluble TREM2 (sTREM2) resulting from shedding of the TREM2 ectodomain can be detected in the cerebrospinal fluid (CSF) and is a surrogate measure of TREM2-mediated microglia function. CSF sTREM2 has been previously reported to increase at different clinical stages of AD, however, alterations in relation to Amyloid β-peptide (Aβ) deposition or additional pathological processes in the amyloid cascade (such as tau pathology or neurodegeneration) remain unclear. In the current cross-sectional study, we employed the biomarker-based classification framework recently proposed by the NIA-AA consensus guidelines, in combination with clinical staging, in order to examine the CSF sTREM2 alterations at early asymptomatic and symptomatic stages of AD. A cross-sectional study of 1027 participants of the Alzheimer's Disease Imaging Initiative (ADNI) cohort, including 43 subjects carrying TREM2 rare genetic variants, was conducted to measure CSF sTREM2 using a previously validated enzyme-linked immunosorbent assay (ELISA). ADNI participants were classified following the A/T/N framework, which we implemented based on the CSF levels of Aβ1-42 (A), phosphorylated tau (T) and total tau as a marker of neurodegeneration (N), at different clinical stages defined by the clinical dementia rating (CDR) score. CSF sTREM2 differed between TREM2 variants, whereas the p.R47H variant had higher CSF sTREM2, p.L211P had lower CSF sTREM2 than non-carriers. We found that CSF sTREM2 increased in early symptomatic stages of late-onset AD but, unexpectedly, we observed decreased CSF sTREM2 levels at the earliest asymptomatic phase when only abnormal Aβ pathology (A+) but no tau pathology or neurodegeneration (TN-), is present. Aβ pathology (A) and tau pathology/neurodegeneration (TN) have differing associations with CSF sTREM2. While tau-related neurodegeneration is associated with an increase in CSF sTREM2, Aβ pathology in the absence of downstream tau-related neurodegeneration is associated with a decrease in CSF sTREM2.


Gastric ulceration in diabetes mellitus: protective role of vitamin C.
The effect of vitamin C administration on gastric acid secretion and ulcer in diabetic rats was studied. Vitamin C (200 mg/kg b.w.) was administered to both streptozotocin-induced diabetic and control groups orally for 28 days. Gastric acid secretion was measured and ulcer was induced using ethanol. Histological changes were observed in the stomach. Basal and stimulated acid secretion in diabetic control rat was significantly (P < 0.01) decreased when compared to vitamin C-treated diabetic group and control. Administration of vitamin C significantly (P < 0.05) increased the histamine-stimulated gastric acid secretion in diabetics than control while reduction in gastric secretion by ranitidine was similar compared with control. Vitamin C treatment significantly (P < 0.05) reduced ulcer index in diabetic group and increased mucus weight when compared with diabetic group which was also confirmed with photomicrographs. The mean body weight of diabetic rats treated with vitamin C was comparable to the control. The blood glucose level was significantly (P < 0.01) reduced in diabetic group given vitamin C (8.9 ± 1.8 mMol/L) compared to the diabetic control (32.2 ± 2.1 g). It is concluded that vitamin C is beneficial in improving gastric acid secretion and protects against ulceration in streptozotocin-induced diabetes mellitus in rats due to its antioxidant potential.


Sp and GATA factors are critical for Apolipoprotein AI downstream enhancer activity in human HepG2 cells.
The factors that bind to the hepatic-specific human apolipoprotein AI (apoAI) 48-bp downstream enhancer (DSE) were identified and characterized by electrophoretic mobility shift assays. A significant homology was shown between the histone 4 (H4) promoters and the hepatic-specific human apoAI DSE at Sp1 and H4TF2 binding sites. Human HepG2 nuclear extracts were used to form four specific complexes with the DSE (referred to as apoAI DSE-1, -2, -3, and -4). The apoAI DSE-1 and -2 complexes showed similar binding specificity to the Sp/H4TF1 consensus site within the apoAI DSE. The apoAI DSE-1 complex was predominantly recognized by anti-Sp1 and Sp3 sera in gel shift assays, indicating that the DSE was recognized by multiple Sp family members. Nuclear extracts that were prepared from retinoic acid treated HepG2 cells showed increased levels of Sp factors in gel shift and Western blot assays. The apoAI DSE-2 complex was identified as H4TF1 and formed in the absence of magnesium chloride. The apoAI DSE-3 complex bound to a consensus GATA element within the DSE that was recognized by recombinant human GATA-6 as well. The apoAI DSE-3 complex was completely disrupted by a GATA-4 antibody in EMSA. GATA-4 and -6 were detected in nuclear extracts prepared from retinoic acid treated HepG2 cells using Western blot assays. The highest apoAI DSE-3 levels were observed with retinoic acid treated HepG2 cell nuclear extracts in EMSA. ApoAI DSE-4 is a multi-factor complex that includes an Sp/H4TF1 factor and either H4TF2 or apoAI DSE-3. Because apoAI DSE mutations revealed transcription defects in transient transfection assays, we conclude that the entire DSE sequence is required for full apoAI transcriptional activity in HepG2 cells.


Color Balance and Fusion for Underwater Image Enhancement.
We introduce an effective technique to enhance the images captured underwater and degraded due to the medium scattering and absorption. Our method is a single image approach that does not require specialized hardware or knowledge about the underwater conditions or scene structure. It builds on the blending of two images that are directly derived from a color-compensated and white-balanced version of the original degraded image. The two images to fusion, as well as their associated weight maps, are defined to promote the transfer of edges and color contrast to the output image. To avoid that the sharp weight map transitions create artifacts in the low frequency components of the reconstructed image, we also adapt a multiscale fusion strategy. Our extensive qualitative and quantitative evaluation reveals that our enhanced images and videos are characterized by better exposedness of the dark regions, improved global contrast, and edges sharpness. Our validation also proves that our algorithm is reasonably independent of the camera settings, and improves the accuracy of several image processing applications, such as image segmentation and keypoint matching.


Analysis of working-side occlusal contacts.
Bilateral interocclusal registrations were made of two working-side mandibular positions of 45 healthy young adults with morphologically good occlusions. The occlusal contacts were analyzed according to frequency and location. A large number of subjects presented unclassified patterns of articulations. In the group with known occlusal schemes, more individuals had "canine guidance" on the left side, whereas the most frequent pattern on the right side was "partial group function."


Improved Recovery of Immunoglobulin Fraction from Egg Yolk of Chicken Immunized with AsialoGM1.
Chicken egg yolk is an abundant, yet inexpensive source of polyclonal antibodies. However, removal of the contaminating lipids and lipoproteins from immunoglobulins of egg yolk (IgY) is considered to be a laborious task during the purification. Liposomal asialoGM1 was used as a model immunogen for raising polyclonal IgY and tested with various methodological approaches. To overcome certain difficulties posed during IgY purification, several detergents (cationic, anionic and non-ionic) were tested for their effect on yolk protein and lipoprotein separation during water dilution processing of IgY. Cetrimide showed a pronounced effect on improving the immunoglobulin separation with only less than 3% of the lipid contaminants as compared to other detergents. The least effective detergent was sodium dodecyl sulphate with 14-35% contaminating lipids. The usefulness of egg yolk acetone powder for long-term storage prior to IgY purification was also determined. The use of acetone precipitated proteins for IgY processing showed a 25-30% loss in antigen specific immunoreactivity despite of an optimum total immunoglobulin recovery of 80%. A combination of delipidation of yolk with 50% acetone and treatment of the resultant acetone precipitated protein with a low ionic buffer (pH 5.5) containing 200 &mgr;M of cetrimide yields electrophoretically homogeneous IgY with an optimum total immunoglobulin recovery of 85-90%. The antigen specific immunoreactivity of anti-asialoGM1 IgY was preserved well during the cetrimide treatment and was found to be higher than all other recovery processes, as tested by radial immunodiffusion and immunoblot assays.


[Pharmacological chaperones: a potential therapeutic treatment for conformational diseases].
Many genetic and neurodegenerative diseases in humans result from protein misfolding and/or aggregation. These diseases are named conformational diseases. As a result, the misfolded non functional proteins are rejected and misrouted by the cellular quality control system, and cannot play their endogenous physiological roles. Specific compounds (ligands, substrates or inhibitors) known as pharmacological chaperones are able to bind and stabilize these misfolded proteins. Their interaction allows the target proteins to escape the quality control system and to be functionally rescued. These pharmacochaperones may possess different intrinsic activity: they can be antagonists (inhibitors), agonists (activators) or allosteric modulators of the target receptors, ionic channels or enzymes. Pharmacological chaperones have obviously a therapeutic potential to treat rare diseases like cystic fibrosis, retinitis pigmentosa, nephrogenic diabetes insipidus, Fabry disease, Gaucher disease, but also for cancers and more frequent and highly invalidant neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease.