Calorimetric study on human erythrocyte glycolysis. Heat production in various metabolic conditions.
The heat production of human erythrocytes was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The heat production connected with the lactate formation was about 17 kcal (71 kJ) per mol lactate formed which corresponded to the sum of heat production due to the formation of lactate from glucose and the heat production due to neutralization. The heat production rate increased as the pH of the suspension increased, corresponding to the increase in lactate formation. Glycolytic inhibitors such as fluoride and monoiodoacetate caused a decrease in the rate of heat production, whereas arsenate induced a large transient increase in heat production associated with a transient increase in lactate formation. Decrease in pyruvate concentration was usually associated with increase in heat production, although the decreased pyruvate concentration was coupled with formation of 2,3-bisphosphoglycerate. When inosine, dihydroxyacetone or D-glyceraldehyde was used as a substrate, an increase in the heat production rate was observed. Addition of methylene blue caused an oxygen uptake which was accompanied by a remarkable increase in heat production rate corresponding to about 160 kcal (670 kJ) per mol oxygen consumed. The value for heat production in red cells in the above-mentioned metabolic conditions was considered in relation to earlier known data on free energy and enthalpy changes of the different metabolic steps in the glycolytic pathway.


Comparative study of virgin olive oil behavior under Rancimat accelerated oxidation conditions and long-term room temperature storage.
Oxidative stability should be one of the most important quality markers of edible oils; nevertheless, it is not recognized as a legal parameter. The results reported in this study highlight the differences in the olive oil oxidation process under Rancimat accelerated conditions with respect to long-term storage at room temperature and clearly show the lack of correlation between shelf life and the Rancimat induction period. A better correlation, although not yet satisfactory, was found when the same oxidation end-point was used in both assays. The parameter K 270, a marker of secondary oxidation products, was the first index to reach the established upper legal limit under Rancimat conditions, whereas at 25 degrees C it was an index of primary oxidation products ( K 232). Furthermore, the ratio of oxidation rate at Rancimat conditions to oxidation rate at 25 degrees C was more than double for secondary oxidation products compared with primary ones. Notable differences were also observed in degradation rates of the different unsaturated fatty acids and in rates of formation of polar oxidation compounds. Moreover, under the Rancimat conditions antioxidants such as o-diphenols and alpha-tocopherol rapidly depleted, and when they had practically disappeared, there was a sharp increase in oxidation indices, such as peroxide value, and in oxidation products. At 25 degrees C, on the other hand, the depletion was much lower.


Fatal hepatitis B in early infancy: the importance of identifying HBsAg-positive pregnant women and providing immunoprophylaxis to their newborns.
Infants born to women who are asymptomatic hepatitis B surface antigen (HBsAg) carriers frequently acquire hepatitis B virus infection in infancy. The spectrum of disease in such affected infants includes mild transient acute hepatitis B, chronic active hepatitis with or without cirrhosis, chronic persistent hepatitis, chronic asymptomatic HBsAg carriage, and, rarely, fulminant fatal hepatitis B. Recently, the administration of hepatitis B immunoglobulin has been demonstrated to reduce the risk of infantile acquisition of hepatitis B virus; hepatitis B vaccine may also be preventive in this setting. Three young infants, aged 8 to 16 weeks, who died of acute fulminant hepatitis were studied. In each instance, the mother was found, retrospectively, to be asymptomatic but HBsAg positive. One of these mothers was hepatitis B e-antigen-negative but hepatitis B e-antibody positive. All three babies were HBsAg positive; two who were tested for hepatitis B core antibody were positive. These three fatalities serve to dramatize both the importance of HBsAg screening of pregnant women, particularly those with demographic factors that place them at increased risk for HBsAg carriage, as well as the significance of effective immunoprophylaxis for hepatitis B in all offspring of women with HBsAg seropositivity.


The Determination of Parkinson's Drugs in Human Urine by Applying Chemometric Methods.
The spectrophotometric-chemometric analysis of levodopa and carbidopa that are used for Parkinson's disease was analyzed without any prior reservation. Parkinson's drugs in the urine sample of a healthy person (never used drugs in his life) were analyzed at the same time spectrophotometrically. The chemometric methods used were partial least squares regression (PLS) and principal component regression (PCR). PLS and PCR were successfully applied as chemometric determination of levodopa and carbidopa in human urine samples. A concentration set including binary mixtures of levodopa and carbidopa in 15 different combinations was randomly prepared in acetate buffer (pH 3.5).). UV spectrophotometry is a relatively inexpensive, reliable, and less time-consuming method. Minitab program was used for absorbance and concentration values. The normalization values for each active substance were good (r2>0.9997). Additionally, experimental data were validated statistically. The results of the analyses of the results revealed high recoveries and low standard deviations. Hence, the results encouraged us to apply the method to drug analysis. The proposed methods are highly sensitive and precise, and therefore they were implemented for the determination of the active substances in the urine sample of a healthy person in triumph.


Thylakoid Protein Phosphorylation Dynamics in a Moss Mutant Lacking SERINE/THREONINE PROTEIN KINASE STN8.
In all eukaryotes, protein phosphorylation is a key regulatory mechanism in several cellular processes, including the acclimation of photosynthesis to environmental cues. Despite being a well-conserved regulatory mechanism in the chloroplasts of land plants, distinct differences in thylakoid protein phosphorylation patterns have emerged from studies on species of different phylogenetic groups. Here, we analyzed thylakoid protein phosphorylation in the moss Physcomitrella patens, assessing the thylakoid phospho-protein profile and dynamics in response to changes in white light intensity. Compared with Arabidopsis (Arabidopsis thaliana), parallel characterization of wild-type P patens and the knockout mutant stn8 (depleted in SER/THR PROTEIN KINASE8 [STN8]) disclosed a moss-specific pattern of thylakoid protein phosphorylation, both with respect to specific targets and to their dynamic phosphorylation in response to environmental cues. Unlike vascular plants, (1) phosphorylation of the PSII protein D1 in P patens was negligible under all light conditions, (2) phosphorylation of the PSII core subunits CP43 and D2 showed only minor changes upon fluctuations in light intensity, and (3) absence of STN8 completely abolished all PSII core protein phosphorylation. Further, we detected light-induced phosphorylation in the minor light harvesting complex (LHC) antenna protein LHCB6, which was dependent on STN8 kinase activity, and found specific phosphorylations on LHCB3. Data presented here provide further insights into the appearance and physiological role of thylakoid protein phosphorylation during evolution of oxygenic photosynthetic organisms and their colonization of land.


Remittive therapy in rheumatoid arthritis: clinical uses and mechanisms of action.
Evidence has been reviewed supporting the conclusion that gold compounds, anti-malarials and D-penicillamine have the capacity to function as immunosuppressive drugs. Moreover, the results indicate that each has a unique site of action, specifically inhibiting the function of only one of the populations of cells likely to be involved in chronic immunologically-mediated inflammation. Gold compounds and anti-malarials appear to be active by virtue of their capacity to depress the function of mononuclear phagocytes, while D-penicillamine acts by inhibiting a number of the activities of T lymphocytes. These results imply that the means by which these drugs suppress rheumatoid inflammation are fundamentally different. Thus, while each of these compounds acts as a selective immunosuppressive agent, the target cell inhibited appears to be different. The conclusion that the remission-inducing drugs have different modes of action in RA is supported by the clinical observation that the success rate of therapy with one is comparable regardless of antecedent therapy with another (125, 126).


Socioeconomic issues and education of neurologic surgery residents in the United States.
The goals of this project were to ascertain the extent to which socioeconomic issues are being formally addressed within neurologic training programs in the United States and to determine the perception of chief neurosurgery residents and program directors regarding training and preparation as it relates to these issues. The chief neurosurgery residents and program directors for the 1995 academic year were identified and mailed a survey with questions regarding the formal training of socioeconomic issues within their programs. Residents indicated that 95% did not believe their residency program provided adequate training in socioeconomic issues; 97% and 95% respectively, did not feel adequately prepared to deal with the business aspects of a medical practice or to deal with insurance companies and the managed care environment; and 87% did not think they were adequately prepared to deal with a lawsuit. Moreover, from 25%-87% did not know the meaning of terms such as capitation, RVUs, PPOs, or IPAs. The program directors indicated that 58% of the programs did not formally deal with socioeconomic issues. This survey indicates that socioeconomic issues are not currently being properly addressed in a large proportion of neurosurgical residency programs. An overwhelming majority of the residents did not feel they are adequately prepared to deal with those nonmedical-surgical aspects of the practice of neurosurgery. This perception was corroborated by the response of the program directors. There appears to be a significant deficiency in the training of neurosurgical residents with regard to socioeconomic issues in the United States.


One-pot synthesis of pyrimidine linked naphthoquinone-fused pyrroles by iodine-mediated multicomponent reactions.
Herein we report iodine-mediated multicomponent reactions for the synthesis of naphthoquinone-fused pyrroles tethered with a pyrimidine moiety. The reaction of aryl methyl ketones (3) or terminal aryl alkynes (5) in the presence of molecular iodine in DMSO medium followed by sequential addition of barbituric acids (2) and 2-amino-1,4-naphthoquinone (1) provides the corresponding three-component hybrid molecules 4 having naphthoquinone-fused pyrroles tethered with a barbituric acid moiety. This three-component reaction proceeds via metal-free C-H oxidation followed by multi-component cyclization forming three new bonds (2 C-C, 1 C-N) in one pot. Alternatively, the same molecules can also be prepared from the reaction of arylglyoxals, 2-aminonaphthoquinone, and barbituric acids in the presence of a catalytic amount of iodine in methanol medium under reflux conditions. The salient features of these methodologies are: one-pot metal-free method, good yields, wide substrate scope, easy purification of products, and the presence of medicinally important naphthoquinone, pyrrole and pyrimidine moieties in the products.


Autologous blood and platelet-rich plasma injection therapy for lateral elbow pain.
Autologous whole blood or platelet-rich plasma (PRP) injections are commonly used to treat lateral elbow pain (also known as tennis elbow or lateral epicondylitis or epicondylalgia). Based on animal models and observational studies, these injections may modulate tendon injury healing, but randomised controlled trials have reported inconsistent results regarding benefit for people with lateral elbow pain. To review current evidence on the benefit and safety of autologous whole blood or platelet-rich plasma (PRP) injection for treatment of people with lateral elbow pain. We searched CENTRAL, MEDLINE, and Embase for published trials, and Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal for ongoing trials, on 18 September 2020. We included all randomised controlled trials (RCTs) and quasi-RCTs comparing autologous whole blood or PRP injection therapy to another therapy (placebo or active treatment, including non-pharmacological therapies, and comparison between PRP and autologous blood) for lateral elbow pain. The primary comparison was PRP versus placebo. Major outcomes were pain relief (≥ 30% or ≥ 50%), mean pain, mean function, treatment success, quality of life, withdrawal due to adverse events, and adverse events; the primary time point was three months. We used standard methodological procedures expected by Cochrane. We included 32 studies with 2337 participants; 56% of participants were female, mean age varied between 36 and 53 years, and mean duration of symptoms ranged from 1 to 22 months. Seven trials had three intervention arms. Ten trials compared autologous blood or PRP injection to placebo injection (primary comparison). Fifteen trials compared autologous blood or PRP injection to glucocorticoid injection. Four studies compared autologous blood to PRP. Two trials compared autologous blood or PRP injection plus tennis elbow strap and exercise versus tennis elbow strap and exercise alone. Two trials compared PRP injection to surgery, and one trial compared PRP injection and dry needling to dry needling alone. Other comparisons include autologous blood versus extracorporeal shock wave therapy; PRP versus arthroscopic surgery; PRP versus laser; and autologous blood versus polidocanol. Most studies were at risk of selection, performance, and detection biases, mainly due to inadequate allocation concealment and lack of participant blinding. We found moderate-certainty evidence (downgraded for bias) to show that autologous blood or PRP injection probably does not provide clinically significant improvement in pain or function compared with placebo injection at three months. Further, low-certainty evidence (downgraded for bias and imprecision) suggests that PRP may not increase risk for adverse events. We are uncertain whether autologous blood or PRP injection improves treatment success (downgraded for bias, imprecision, and indirectness) or withdrawals due to adverse events (downgraded for bias and twice for imprecision). No studies measured health-related quality of life, and no studies reported pain relief (> 30% or 50%) at three months. At three months, mean pain was 3.7 points (0 to 10; 0 is best) with placebo and 0.16 points better (95% confidence interval (CI) 0.60 better to 0.29 worse; 8 studies, 523 participants) with autologous blood or PRP injection, for absolute improvement of 1.6% better (6% better to 3% worse). At three months, mean function was 27.5 points (0 to 100; 0 is best) with placebo and 1.86 points better (95% CI 4.9 better to 1.25 worse; 8 studies, 502 participants) with autologous blood or PRP injection, for absolute benefit of 1.9% (5% better to 1% worse), and treatment success was 121 out of 185 (65%) with placebo versus 125 out of 187 (67%) with autologous blood or PRP injection (risk ratio (RR) 1.00; 95% CI 0.83 to 1.19; 4 studies, 372 participants), for absolute improvement of 0% (11.1% lower to 12.4% higher). Regarding harm, we found very low-certainty evidence to suggest that we are uncertain whether withdrawal rates due to adverse events differed. Low-certainty evidence suggests that autologous blood or PRP injection may not increase adverse events compared with placebo injection. Withdrawal due to adverse events occurred in 3 out of 39 (8%) participants treated with placebo versus 1 out of 41 (2%) treated with autologous blood or PRP injection (RR 0.32, 95% CI 0.03 to 2.92; 1 study), for an absolute difference of 5.2% fewer (7.5% fewer to 14.8% more). Adverse event rates were 35 out of 208 (17%) with placebo versus 41 out of 217 (19%) with autologous blood or PRP injection (RR 1.14, 95% CI 0.76 to 1.72; 5 studies; 425 participants), for an absolute difference of 2.4% more (4% fewer to 12% more). At six and twelve months, no clinically important benefit for mean pain or function was observed with autologous blood or PRP injection compared with placebo injection. Data in this review do not support the use of autologous blood or PRP injection for treatment of lateral elbow pain. These injections probably provide little or no clinically important benefit for pain or function (moderate-certainty evidence), and it is uncertain (very low-certainty evidence) whether they improve treatment success and pain relief > 50%, or increase withdrawal due to adverse events. Although risk for harm may not be increased compared with placebo injection (low-certainty evidence), injection therapies cause pain and carry a small risk of infection. With no evidence of benefit, the costs and risks are not justified.


Moyamoya disease: a comparison of long term outcome of conservative and surgical treatment in India.
Revascularization surgery (RS) is the therapy of choice in moyamoya disease (MMD). Due to rarity of disease and ethical concerns, randomized controlled trials about the treatment options are lacking. Very little information is available on the long-term outcome of conservatively treated moyamoya patients. We compared the long-term outcome of moyamoya patients treated conservatively to those who underwent RS. Our study population included all patients with moyamoya disease/syndrome from 2002 to 2012. The demographic, clinical characteristic and imaging details were reviewed. The outcome was obtained prospectively. Of the 36 patients, 26 (72.2%) had MMD and 10 (27.8%) had moyamoya syndrome. The median age at onset of symptoms was 17.5 years (range, 10 months-55 years). Fifteen patients belonged to pediatric group and 21 were adults. All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. Twenty (55.6%) patients received conservative treatment and 16 (44.4%) underwent revascularization procedures. The median duration of follow-up was 28 months (range, 3-90 months). Three (18%) of the surgically treated patients had recurrent ischemic events on follow-up, but none of the conservatively treated patients had events. An excellent outcome (Modified Rankin Scale of ≤2) was seen in 12 (75%) surgically treated and 16 (94%) conservatively treated patients (p=0.17). Compared to East Asians, our patients had a lower stroke recurrence rate and good functional outcome even with conservative treatment. Future studies should focus on clinical and imaging predictors of progression to select moyamoya patients for RS.


Application of XAD-resin based passive air samplers to assess local (roadside) and regional patterns of persistent organic pollutants.
We used XAD-resin based passive air samplers (PAS) to measure atmospheric levels of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) at five ombrotrophic bogs in Eastern Canada. The aims of our study were to investigate the influence of local roads on contaminant levels in the bogs, to derive the regional pattern of atmospheric concentrations, and to assess the uncertainties of the method. Expanded uncertainties based on the duplicate PAS deployed at 24 sites were good for the PAHs, while the deployment period of approx. 100 days was too short to yield acceptable uncertainties for PCBs. The regional PAH distribution was in good agreement with the calculated source proximity of the sampled bogs. We conclude that XAD-resin based PAS deployed for comparatively short periods are well suited for measuring atmospheric concentrations of volatile PAHs, while in remote regions longer deployment is necessary for less volatile PAHs and for PCBs.


Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection.
Leukocyte adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury as well as in host defense against various infectious microorganisms. Administration of monoclonal antibodies directed against the beta chain of the leukocyte integrins inhibits leukocyte-endothelial-cell adherence and has been reported to modulate ischemia-reperfusion and inflammatory injury. However, such inhibition of adhesion molecule function adversely affects resistance to infection. The following studies were carried out to determine whether monoclonal antibodies to other adhesion molecules, including L-selectin (CD62L), and CD11a (the alpha chain of LFA-1), also increase susceptibility to infection. New Zealand White rabbits were shaved and given subcutaneous injections on their dorsa with 10(9) CFU of Staphylococcus aureus ATCC 25923 at two sites and with 10(8) CFU at two sites. A second set of rabbits were given subcutaneous injections with 10(8) CFU of P. aeruginosa ATCC 27853 at two sites and with 10(7) CFUs at two sites. The animals were monitored for 1 week. There were three blinded experimental groups: controls given saline and two groups given blocking monoclonal antibodies to either L-selectin (Dreg-200) or CD11a (R7.1). In contrast to monoclonal antibodies to CD18, none of the monoclonal antibodies significantly increased the risk of abscess formation by S. aureus, although inhibition of CD11a increased the rate of abscess formation by P. aeruginosa.


A single chip electron spin resonance detector based on a single high electron mobility transistor.
Single-chip microwave oscillators are promising devices for inductive electron spin resonance spectroscopy (ESR) experiments on nanoliter and subnanoliter samples. Two major problems of the previously reported designs were the large minimum microwave magnetic field (0.1-0.7 mT) and large power consumption (0.5-200 mW), severely limiting their use for the investigation of samples having long relaxation times and for operation at low temperatures. Here we report on the design and characterization of a single-chip ESR detector operating with a microwave magnetic field and a power consumption orders of magnitude lower compared with previous designs. These significant improvements are mainly due to the use of a high electron mobility transistor (HEMT) technology instead of a complementary metal-oxide semiconductor (CMOS) technology. The realized single-chip ESR detector, which operates at 11.2 GHz, consists of an LC Colpitts oscillator realized with a single high-electron mobility transistor and a co-integrated single turn planar coil having a diameter of 440 μm. The realized detector operates from 300 K down to 1.4 K, at least. Its minimum microwave magnetic field is 0.4 μT at 300 K and 0.06 μT at 1.4 K, whereas its power consumption is 90 μW at 300 K and 4 μW at 1.4 K, respectively. The experimental spin sensitivity on a sensitive volume of about 30 nL, as measured with a single crystal of α,γ-bisdiphenylene-β-phenylallyl (BDPA)/benzene complex, is of 8 × 1010 spins/Hz1/2 at 300 K and 2 × 109 spins/Hz1/2 at 10 K, respectively. In a volume of about 100 pL, located in proximity to the coil wire, the spin sensitivity improves by two orders of magnitude.


Improving functional form in cross-sectional regression studies to capture the non-linear safety effects of roadway attributes-Freeway median width case study.
Crash modification factors (CMFs) for several roadway attributes are based on cross-sectional regression models, in the main because of the lack of data for the preferred observational before-after study. In developing these models, little attention has been paid to those functional forms that reflect the reality that CMFs should not be single-valued, as most available ones are, but should vary with application circumstance. Using a full Bayesian Markov Chain Monte Carlo (MCMC) approach, this study aimed to improve the functional forms used to derive CMFs in cross-sectional regression models, with a focus on capturing the variability inherent in crash modification functions (CMFunctions). The estimated CMFunction for target crashes for freeway median width, used for a case study, indicates that the approach is capable of developing a function that can capture the logical reality that the CMF for a given change in a feature's value depends not only on the amount of the change but also on the original value. The results highlight the importance of using the functional forms that can capture non-linear effects of road attributes for CMF estimation in cross-sectional models. The case study provides credible CMFs for assessing the safety implications of decisions on freeway median width that could be used in improving current design practice.


Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior.
The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior.


Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases.
There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding. This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB. A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]). In this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.


Factor VIII and IX gene polymorphisms and carrier analysis in Indian population.
The efficacy of the three common intra- and extragenic polymorphic sites of the factor VIII and IX genes has been examined in the Indian population, with an aim to develop a strategy that would be accurate and informative, yet economical. The approach for hemophilia A carrier detection includes tests for BclI, XbaI, and TaqI polymorphic sites for introns 18 and 22 and the extragenic locus St 14, respectively, whereas for hemophilia B, tests include detection of TaqI, DdeI, and HhaI polymorphic sites for introns 4 and 1, and the 3' flanking region of the factor IX gene, respectively. In hemophilia A, the cumulative efficiency of these three polymorphisms has been found to be 100%, since all 37 tested families were informative for at least one of these three polymorphisms. It is of interest to note that a case of recombination between St 14 and the factor VIII gene was also observed. Of the 47 unrelated X chromosomes examined (normal = 10, factor VIII:C deficiency = 37), heterozygosity for BclI, XbaI, and St 14 was found to be 47%, 36%, and 86%, respectively, in the factor VIII gene. However, when 37 unrelated X chromosomes (normal = 10, factor IX:C = 27) were analyzed for polymorphism with TaqI, DdeI, and HhaI, it was found that the polymorphism detection rate was only 18% for the TaqI site but 45% each for the DdeI and HhaI sites, in the factor IX gene. This indicates a low effectiveness of the TaqI restriction site in carrier analysis of hemophilia B families in our population.


Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes.
Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4) and acute insulin response (OR = 0.65, CI = 0.44-0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21), fat-BMI (OR = 1.22, CI = 1.08-1.38), waist (OR = 1.13, CI = 1.04-1.22), and cholesterol (OR = 5.60, CI = 0.99-31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2), p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (chi(2), p = 0.01). The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.


Fat embolism syndrome.
Although first reported in 1862, the fat embolism syndrome continues to arouse controversy. Current views on its pathophysiology, diagnosis, treatment and prophylaxis are reviewed here.


Quantification through the surface EMG of muscle fatigue and recovery during successive isometric contractions.
The surface electromyogram (EMG) was analyzed from above the handgrip muscles of the forearm in six male volunteer graduate and medical students during brief and fatiguing isometric contractions in order to assess the influence of successive isometric contractions on the amplitude and frequency components of the surface EMG. Isometric contractions were sustained at three tensions; 25, 40 and 70% of each individual's maximum voluntary strength (MVC). Two successive isometric contractions were conducted in each series of experiments. The interval between these contractions was set at 2, 4, 6, 8, 10, or 12 min. In the first series of experiments, the second contraction in the series consisted of a fatiguing isometric contraction conducted at the same tension as the first contraction. In the second series of experiments, the second contraction was an MVC. From the data, a computer program was written to predict the degree of fatigue and recovery following fatiguing isometric contractions. The program was based on an analysis of the frequency components of the EMG and proved to be quite useful for showing fatigue and recovery in this muscle group.


Using Drosophila behavioral assays to characterize terebrid venom-peptide bioactivity.
The number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and Tsu1.1 from Terebra subulata. Our results indicate that Tv1 and Tsu1.1 have distinct bioactivity. Tv1 (100 µM) had an antinociceptive effect in adult Drosophila using a thermal nociception assay to measure heat avoidance. Alternatively, Tsu1.1 (100 µM) increased food intake. These findings describe the first functional bioactivity of terebrid venom peptides in relation to pain and diet and indicate that Tv1 and Tsu1.1 may, respectively, act as antinociceptive and orexigenic agents. Tv1 and Tsu1.1 are distinct from previously identified venom peptides, expanding the toolkit of peptides that can potentially be used to investigate the physiological mechanisms of pain and diet.


Score for atrial fibrillation detection in acute stroke and transient ischemic attack patients in a Brazilian population: the acute stroke atrial fibrillation scoring system.
Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings. We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS). A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76). Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement.


Neurofilament phosphorylation in neuronal perikarya following axotomy: a study of rat spinal cord with ventral and dorsal root transection.
Rat spinal cord was stained by indirect immunofluorescence with 11 neurofilament monoclonal antibodies that recognize phosphorylated epitopes. All monoclonals were axon-specific in this location. The large motoneurons containing bundles of neurofilaments did not stain and the pattern remained unchanged after transection of the sciatic nerve in the thigh. With nine monoclonals, stained motoneurons were observed in the ventral horns 3 days, 5 days, 1 week, and 2 weeks after transection of the ventral roots close to the spinal cord. The abnormal motoneurons were typically scattered among normal (i.e., nonstained) cells. Even in animals showing the most severe reaction, the whole motoneuron population at the site of rhizotomy was not affected, stained and nonstained perikarya often coexisting side by side. Stained motoneurons were no longer observed 3 weeks after ventral root transection. Changes in neuronal immunoreactivity were also observed after dorsal root transection. However, a different population was affected, i.e., middle-sized neurons in dorsal horns and at the base of ventral horns. With two monoclonals (A9 and D21), cell bodies remained negative following all operations. It is concluded that axotomy in proximity of the cell body may induce certain neurofilament phosphorylation events in motor neuron perikarya, whereas other phosphorylation events remain confined to the axons under these experimental conditions. The absence of changes after transection of the sciatic nerve in the thigh suggests that neurofilament phosphorylation is a reaction to cell injury rather than a cellular event related to nerve regeneration.


Anti-HIV-1 antibody-dependent cellular cytotoxicity: is there more to antibodies than neutralization?
An increasing body of evidence suggests that nonneutralizing Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC) contribute to protection against HIV-1 acquisition. We discuss recent advances in anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC antibodies and the mechanisms of HIV-1 resistance to ADCC. ADCC activities of broadly neutralizing and nonneutralizing monoclonal antibody panels were recently characterized in vitro against several lab-adapted and primary isolates of HIV-1. ADCC activity of these monoclonal antibodies generally correlated with binding to infected cells and were greater against the lab-adapted strains compared with primary HIV-1 isolates. Several recent studies in mouse and macaque models of HIV-1 infection suggest Fc-mediated effector functions contribute to the protective efficacy of broadly neutralizing antibodies and exert immune pressure on HIV-1 in vivo. An increasing body of evidence suggests that ADCC-mediating antibodies, particularly when combined with neutralizing functions, can facilitate prevention and control of HIV-1. The precise mechanisms of partial protection conferred by nonneutralizing antibodies in vivo remain unclear and will need to be fully investigated in order to realize their full potential for HIV-1 vaccines.


Temperature management for out-of-hospital cardiac arrest.
More than 300,000 Americans suffer a cardiac arrest outside of the hospital each year and even among those who are successfully resuscitated and survive to hospital admission, outcomes remain poor. Temperature management (previously known as therapeutic hypothermia) is the only intervention that has been reproducibly demonstrated to ameliorate the neurologic injury that follows cardiac arrest. The results of a recent large randomized controlled trial have highlighted the uncertainty about temperature management strategies following cardiac arrest. This article reviews the issues and recommendations.


Applications of Healthcare Robots in Combating the COVID-19 Pandemic.
Due to the increasing number of COVID-19 cases, there is a remarkable demand for robots, especially in the clinical sector. SARS-CoV-2 mainly propagates due to close human interactions and contaminated surfaces, and hence, maintaining social distancing has become a mandatory preventive measure. This generates the need to treat patients with minimal doctor-patient interaction. Introducing robots in the healthcare sector protects the frontline healthcare workers from getting exposed to the coronavirus as well as decreases the need for medical personnel as robots can partially take over some medical roles. The aim of this paper is to highlight the emerging role of robotic applications in the healthcare sector and allied areas. To this end, a systematic review was conducted regarding the various robots that have been implemented worldwide during the COVID-19 pandemic to attenuate and contain the virus. The results obtained from this study reveal that the implementation of robotics into the healthcare field has a substantial effect in controlling the spread of SARS-CoV-2, as it blocks coronavirus propagation between patients and healthcare workers, along with other advantages such as disinfection or cleaning.


Improving the scientific misconduct hearing process.
The overturning and withdrawal of several of the Office of Research Integrity's (ORI's) findings of scientific misconduct have called its role into question. The contested findings of scientific misconduct that have been tried before the hearing body have been based on lengthy and expensive ORI investigations. How could ORI have failed to prove its findings of scientific misconduct after the commitment of substantial resources that far exceed those devoted during institutional investigations? One reason may be that the current hearing process makes it difficult or impossible for ORI, institutions, or individuals to prove scientific misconduct. The hearing process has been criticized by discouraged whistleblowers who believe that their allegations of scientific misconduct should have been upheld, and by the accused for the expensive and protracted nature of the proceedings. The following article examines problems in the scientific misconduct hearing process and suggests that the process could be improved by letting administrative law judges, patent attorneys, and a scientific majority decide these cases.


Social and psychological factors in the distribution of STD in male clinic attenders. III Sexual activity.
We report on the relation between various aspects of sexual activity and risk of infection with sexually transmitted disease (STD) in two groups of men attending an STD clinic. Sexual promiscuity appeared to have little effect on the distribution of most STDs, showing a strong association only with gonorrhoea. This finding was contrary to expectation but consistent with the results reported in the first two papers in this series. In contrast to promiscuity, however, sexual orientation subgroups showed a sharp difference in incidence of the major STDs. Hepatitis and syphilis occurred equally commonly among bisexual and homosexual men, but much less commonly among heterosexuals; NSU occurred more commonly among heterosexual men; and gonorrhoea, though common in all three groups, occurred most commonly in bisexual men and least commonly among heterosexuals. For certain STDs the form of intercourse may be as important a risk factor as sexual promiscuity but the precise mechanisms by which sexual orientation influences risk of STD remain undefined.


Clinical outcome of endoscopic retrograde cholangiopancreatography for choledocholithiasis in end-stage renal disease patients on hemodialysis.
Endoscopic retrograde cholangiopancreatography (ERCP) is used as a curative method for choledocholithiasis, but little is known about ERCP for patients with end-stage renal disease (ESRD) on hemodialysis (HD). The aim of the current study was to evaluate the efficacy and safety of ERCP for patients with ESRD on HD and to identify the risk factors of ERCP-related bleeding. The medical records of 61 ESRD patients with choledocholithiasis who underwent ERCP were retrospectively investigated with respect to successful bile duct stone removal and procedure-related adverse events such as pancreatitis, bleeding, and cholangitis. For the study subjects, the overall stone removal success rate was 96.7%, and the overall ERCP-related adverse event rate was 21.3% (pancreatitis, 4.9%; bleeding, 13.1%; cholangitis, 6.6%). Endoscopic sphincterotomy (EST) was found to be associated with hemorrhage (p=0.02), and the occurrence of hemorrhage in patients who underwent EST with or without endoscopic papillary balloon dilation (EPBD) was significantly higher than that in patients who underwent EPBD alone (Odds ratio 1.27, 95% confidence interval 1.075-1.493, p=0.02). ERCP for ESRD patients was found to be feasible and safe. However, EST was significantly related to hemorrhagic events. EPBD reduced the risk of hemorrhage and was as effective as EST in terms of stone removal.


Prevention of traffic accidents: the assessment of perceptual-motor alterations before obtaining a driving license. A longitudinal study of the first years of driving.
A longitudinal study was designed with two objectives: first, to provide a wide cognitive, personality and social description of new drivers before they started to drive cars. Second, to examine the relationship between cognitive and other characteristics drivers had before obtaining their driving license and the number and type of accidents they were involved in during the first years as drivers. The longitudinal study started in 1997 and ended in 2002. The first assessment was made up of 241 individuals at the time they enrolled on the driving course. The follow-up evaluation in the year 2002 was carried out on 144 components of the initial sample after five years driving. Age, gender and education level were matched to represent the population of Spain. Participants were assessed with the Bender Test for visual-motor ability, the B101 Test for practical intelligence, the B19 Test for visual-motor bi-manual coordination, and the TKK-1108 for speed anticipation. Personality was also evaluated with the Rorschach test and the PSY (Psychological Assessment Questionnaire). Five years later, a new examination of all those variables was made as well as a structured interview with each participant in order to collect data relating to significant life events during that time, driving habits, opinions in relation to certain traffic rules and information on accidents, incidents and/or sanctions. Serious and/or minor accidents are concentrated on a few drivers. Accidentality is not related to gender or age, but educational level is related to serious accidents. The number of accidents (severe or minor ones) cannot be predicted if considered as a continuous variable, but it is possible if considered as a discrete variable. In this case two different cognitive profiles account for the number and type of accidents. The number and type of accidents during their first years of driving are related to the cognitive profiles of drivers assessed before they obtained their driving license.


Cardiac transplantation: postoperative chest radiographs.
The preoperative and postoperative chest radiographs of 44 patients undergoing 45 orthotopic cardiac allografts were evaluated retrospectively. Patients were followed from two months to four years postoperatively. Radiographic findings were correlated with echocardiograms and endocardial biopsies. The postoperative cardio-pericardial silhouette stabilized in size by six months. Contrary to previous reports, any marked increase in size of the cardiac silhouette in this series was due to pericardial effusion and not to cardiac rejection. Unusual postoperative features of the chest radiographs included calcification of the residual native left atrium, localized pericardial effusion simulating a left ventricular aneurysm, and a prominent left atrial appendage.


Constructing predictive models of human running.
Running is an essential mode of human locomotion, during which ballistic aerial phases alternate with phases when a single foot contacts the ground. The spring-loaded inverted pendulum (SLIP) provides a starting point for modelling running, and generates ground reaction forces that resemble those of the centre of mass (CoM) of a human runner. Here, we show that while SLIP reproduces within-step kinematics of the CoM in three dimensions, it fails to reproduce stability and predict future motions. We construct SLIP control models using data-driven Floquet analysis, and show how these models may be used to obtain predictive models of human running with six additional states comprising the position and velocity of the swing-leg ankle. Our methods are general, and may be applied to any rhythmic physical system. We provide an approach for identifying an event-driven linear controller that approximates an observed stabilization strategy, and for producing a reduced-state model which closely recovers the observed dynamics.


The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast.
Fluorescent nanodiamonds are frequently used as biolabels. They have also recently been established for magnetic resonance and temperature sensing at the nanoscale level. To properly use them in cell biology, we first have to understand their intracellular fate. Here, we investigated, for the first time, what happens to diamond particles during and after cell division in yeast (Saccharomyces cerevisiae) cells. More concretely, our goal was to answer the question of whether nanodiamonds remain in the mother cells or end up in the daughter cells. Yeast cells are widely used as a model organism in aging and biotechnology research, and they are particularly interesting because their asymmetric cell division leads to morphologically different mother and daughter cells. Although yeast cells have a mechanism to prevent potentially harmful substances from entering the daughter cells, we found an increased number of diamond particles in daughter cells. Additionally, we found substantial excretion of particles, which has not been reported for mammalian cells. We also investigated what types of movement diamond particles undergo in the cells. Finally, we also compared bare nanodiamonds with lipid-coated diamonds, and there were no significant differences in respect to either movement or intracellular fate.


Computerized Simple Reaction Time and Balance in Nondemented Parkinson's Patients.
Parkinson's disease (PD) patients are known to suffer from subtle cognitive and balance deficits from the early stages although they usually manifest in advanced stages. Postural instability (PI) has been correlated with slower information processing speed. Simple reaction time (SRT) tasks can be used to measure the speed of information processing. The main objective of this study was to examine the usefulness of SRT as a valid predictor of balance in PD, thus providing a simple and complementary assessment method. This cross-sectional study included 52 PD patients without dementia who were evaluated for balance using the pull test (PT) maneuver and Biodex® limits of stability (LOS). In addition, a reaction time task was used to measure processing speed. Correlation and linear regression analyses were performed. The performance of SRT tasks was correlated with the evaluation of LOS% and PT, suggesting that the SRT may be a predictor of balance performance. Longer reaction time and poorer postural stability were also associated with disease duration but not with age. Poor performance in a simple reaction task can predict altered PI and can complement staging and evaluation in PD patients.


Probing Site-Specific Structural Information of Peptides at Model Membrane Interface In Situ.
Isotope labeling is a powerful technique to probe detailed structures of biological molecules with a variety of analytical methods such as NMR and vibrational spectroscopies. It is important to obtain molecular structural information on biological molecules at interfaces such as cell membranes, but it is challenging to use the isotope labeling method to study interfacial biomolecules. Here, by individually (13)C═(16)O labeling ten residues of a peptide, Ovispirin-1, we have demonstrated for the first time that a site-specific environment of membrane associated peptide can be probed by the submonolayer surface sensitive sum frequency generation (SFG) vibrational spectroscopy in situ. With the peptide associated with a single lipid bilayer, the sinusoidal trend of the SFG line width and peak-center frequency suggests that the peptide is located at the interface beneath the lipid headgroup region. The constructive interferences between the isotope labeled peaks and the main peptide amide I peak contributed by the unlabeled components were used to determine the membrane orientation of the peptide. From the SFG spectral peak-center frequency, line width, and polarization dependence of the isotope labeled units, we deduced structural information on individual units of the peptide associated with a model cell membrane. We also performed molecular dynamics (MD) simulations to understand peptide-membrane interactions. The physical pictures described by simulation agree well with the SFG experimental result. This research demonstrates the feasibility and power of using isotope labeling SFG to probe molecular structures of interfacial biological molecules in situ in real time.


Synthesis and application of Fmoc-hydrazine for the quantitative determination of saccharides by reversed-phase high-performance liquid chromatography in the low and subpicomole range.
A new derivatization reagent, Fmoc-hydrazine, has been synthesized from the reaction of Fmoc-chloroformate with hydrazine as a precolumn fluorometric labeling reagent for reducing sugars such as glucose, galactose, mannose, fructose, fucose, ribose, xylose, arabinose, lactose, and maltose. The optimization of derivatization conditions was examined in detail. Using a reversed-phase high-performance C-8 column and a mobile phase consisting of acetonitrile-aqueous acetic acid, seven sugar derivatives were separated under either isocratic or gradient conditions within 20 min. The Fmoc-hydrazine and sugar Fmoc-hydrazone derivatives exhibit excellent stability. The extent of the hydrazone formation was 77 and 82% for mannose and fucose as assessed by Dionex high-performance anion-exchange chromatography with pulsed amperometric detection. Linear calibration graphs were established in the range from 0.5 to 2 pmol and 12 to 110 pmol for individual sugar derivatives. The determination limits were 0.05-0.09 pmol for mannose, galactose, and ribose; 0.1 pmol for maltose, xylose, and glucose; 0.2 pmol for fucose and lactose; 0.3 pmol for arabinose; and 0.4 pmol for fructose. The component monosaccharides of ultramicroquantities of two glycoproteins (e.g., from 7 ng fetuin and ovalbumin) were determined in the subpicomole range.


Simulation of functional tricuspid regurgitation using an isolated porcine heart model.
The results of tricuspid annuloplasty to treat functional tricuspid regurgitation (FTR) are sometimes suboptimal, and alternative techniques are needed. In the absence of reliable FTR models, and in an effort to minimize the need for animal experiments, a reproducible bench-model was developed of FTR, that allowed the simulation of the anatomic features of the condition. A fresh porcine heart was mounted on a rigid support that was placed into a basin filled with saline; a closed circuit was then created with a centrifugal pump, equipped with connection tubes. The inflow tube of the pump conveyed saline from the basin to the pump; the outflow cannula was inserted through the pulmonary artery, across the pulmonary valve, into the right ventricle. The pump was activated to pressurize the right ventricle, thus inducing tricuspid valve regurgitation (TVR). The regurgitant flow through the valve was quantified using a flow-meter. Radiopaque markers were sutured to the head of each papillary muscle and to the tricuspid annulus, in order to trace the geometric changes of the tricuspid valve at increasing pump rates, using fluoroscopy. The efficacy of the bench-model was validated with 10 hearts. The TVR was increased proportionally with the right ventricular pressure (RVP) (TVR = 0.089xRVP - 1.515; R2 = 0.89). The increase in TVR was associated with increases in the annular-to-papillary muscles distance (APML) (TVR = 0.059xAPML - 2.94; R2 = 0.96), of the inter-papillary muscles distance (PMD) (TVR = 0.058xPMD - 8.58; R2 = 0.94), and of the triscuspid annular dilatation (TAD) (TVR = 0.05xTAD - 1.85; R2 = 0.89). Of these parameters, APML was the strongest predictor of TVR. The porcine heart bench model represents a reproducible system to simulate the physiopathology of FTR, and has the potential to serve as a complementary method for the evaluation of new 'in vitro' technologies and therapies for FTR.


Quantitative analysis for the effect of the thermal physical property parameter of adhesive on the thermal performance of the quadrupolar fiber coil.
As a high-precision angular sensor, the fiber optic gyroscope (FOG) usually shows high sensitivity to disturbances of the environmental temperature. The thermal performance of the FOG will be directly affected by the selection of adhesive for adhesion inside the fiber coil, however, the current research on this is very rare. This paper is focusing the question above; firstly, the influence mechanism of temperature and stress on the non-reciprocity phase difference of the fiber coil is analyzed, and a model of fiber coil thermal-induced drift error is built. Secondly, the fiber coil three-dimensional simulation model including fiber core, coating layer, adhesive and various materials is built, and the accuracy of the model is verified by simulation and experiment. In the end, the influence of six thermal physical property parameters of adhesive material on the thermal performance of the FOG is analyzed quantitatively and the degree of influence from high to low is Young's modulus, Poisson's ratio, specific heat capacity, density and thermal conductivity. Results show that when choosing the adhesive, decreasing the thermal expansion coefficient, improving the young's modulus, reducing the poisson's ratio, reducing the heat capacity, reducing the density and increasing the thermal conductivity within a certain scope will be conducive to inhibit thermal-induced error of the FOG. And further prove that, the thermal stress distribution inside the fiber coil has more influence on the thermal performance of the FOG than the temperature field distribution. These findings are very helpful to chose and produce adhesive of fiber coil and improve the thermal performance of FOG.


The progressive making of a foremost chiropractic researcher: Fred Illi from Geneva.
Until after the workshop on the research status of Spinal Manipulative Therapy at the National Institute of Neurological and Communicating Disorders and Strokes (NINCDS) in Bethesda, Maryland, in 1975, research had been a very elusive yet critical part of chiropractic evolution. In the past, chiropractic education emphasized basic sciences for legitimacy. To increase their competitive edge, chiropractors all too frequently looked to medical research rather than conducting research of their own. A few exceptionally gifted individuals and agencies within the profession developed new paradigms, improved modalities, and clinical mastery. Very little descriptive information has been made available to assess either these individuals or their achievements. With more than half the profession having less than 10 yr of practice, it becomes necessary to kindle a reappraisal of what once was in the particular area of chiropractic research. The case of Fred Illi has been chosen to illustrate the inherent difficulties that faced anyone bold enough to try and coherent enough to be successful.


Squamous cell carcinoma in trophic ulcer cases.
Two cases having trophic ulcer over the heel, for long time, later developed squamous cell carcinoma are reported, because of its paucity in literature. Various factors blamed for carcinomatous change are enumerated.


Histologic tissue response to furcation perforation repair using mineral trioxide aggregate or dental pulp stem cells loaded onto treated dentin matrix or tricalcium phosphate.
The aim of this study is to compare the effect of treated dentine matrix (TDM) and tricalcium phosphate (TCP) scaffolds on odontogenic differentiation and mineralization of dental pulp stem cells (DPSCs) in furcation perforations created in the pulp chamber floor of premolar teeth in dogs. DPSCs were isolated and cultured from the dental pulp of the maxillary left second and third premolars of dogs. The DPSCs were loaded on TCP (SC+TCP) and TDM (SC+TDM) scaffolds and inserted into intentionally perforated pulp chamber floors of premolars in dogs; six teeth were used for each group. Three more groups of six specimens were created, and mineral trioxide aggregate (MTA), TDM, and TCP were inserted into the perforations to act as controls. An intact premolar and no treatment in the perforation site were used as positive and negative controls respectively. After 3 months, the animals were sacrificed and the type of inflammation, presence of dentine, continuation and type of cementum, type of connective tissue, and presence of foreign body reaction were evaluated, and significant differences were between groups determined using the Fisher's exact test. The evaluation of the amount of inflammation and the percentage of new bone formation was evaluated using the Mann-Whitney U test. The negative control group was associated with severe inflammation and granulation tissue formation. In the positive control group, intact periodontal tissues and no inflammation were observed. Dentine bridge formation was not seen in specimens of any group. The specimens in the SC+TDM group were associated with significantly more bone formation than other groups (P < 0.001). The amount of inflammation was less than 10 % in specimens of all groups with the exception of three specimens in the TCP group that were categorized as 10-30 %. Chronic inflammation without foreign body reactions was the major pattern of inflammation in groups. Formation of cementum with a cellular and continuous appearance was seen in all specimens. SC+TDM was associated with significantly more bone formation when used to repair uninfected furcation perforations in the premolar teeth of dogs. Application of TDM as a biological scaffold in combination with DPSCs may offer an advantage during the repair of root perforation defects.


Association of toxin-producing fungi with disease in broilers.
An episode of suboptimal growth, poor feathering and behavioural abnormalities in broilers in Scotland during the winter of 1980-81 is described. This was considered to be associated with mould-contaminated maize and wheat components of the feed, from which fusaria were isolated in persistently high numbers. Four species, Fusarium culmorum, F tricinctum, F nivale and F moniliforme, were identified. Chloroform extracts of the raw materials and of an artificial medium in which three of the Fusarium species were cultured proved toxic to tissue cultures of a human epithelial cell line (HEp II). Specific identification by thin layer chromatography of the mycotoxins deoxynivalenol, zearalenone and diacetoxyscirpenol was achieved in some extracts. In addition, several other areas of the chromatograms were found to be toxic in the HEp II cell system and these may contain toxins for which standards were not available or, alternatively, previously uncharacterised fungal metabolites. It was concluded that the toxins produced by the fusaria were major contributing factors to the disease symptoms shown by the birds.


Dramatic effect of ethosuximide on epileptic negative myoclonus: implications for the neurophysiological mechanism.
Epileptic negative myoclonus (ENM) is a recently defined epileptic seizure type seen in various epileptic syndromes. Although the long-term prognosis appears to be favorable, the treatment of localization-related epilepsy (LRE) with ENM in childhood is sometimes difficult due to the apparently pharmaco-resistant nature of ENM. We evaluated the effects of antiepileptic drugs (AEDs) in 10 patients with ENM. Carbamazepine was administered to eight patients, none of whom improved. Responses to clonazepam and valproic acid were unpredictable, whereas ethosuximide (ESM) achieved complete control of ENM in all six cases treated with this drug as adjunctive therapy. The pharmacological responses of ENM to CBZ and ESM were quite similar to those of absence seizures. According to the SPECT and ictal EEG findings in addition to the pharmacological responses from this study, we favor to postulate that ENM is produced by a direct inhibitory action on the motor cortex resulting in the interruption of voluntary muscle contraction as generated by sharp-slow wave complexes, compatible with the mechanism considered to underlie absence seizures. ENM are refractory to treatment and persisting if the wrong AEDs, such as PHT or CBZ, are selected at the diagnosis of LRE. We recommended a trial of ESM when ENM develops during the clinical course of LRE regardless of etiology.


Effect of storage on serum vitamin B12 and folate stability.
To facilitate transport from remote locations, the stability of vitamin B12 and folate was investigated in serum specimens. Serum vitamin B12 proved to be highly unstable, emphasizing that specimens should be frozen if not analyzed immediately. Light protection is necessary if the sample cannot be analyzed within 4 hours. In contrast, folate is a more robust analyte. In refrigerated serum specimens, folate was stable up to 7 days of storage. In situations where specimen stability is important, vitamin B12 status is better assessed with serum or urine methylmalonic acid measurements. Although folate status can be assessed in a similar fashion with homocysteine, specimen stability indicates that direct measurement of folate is a better strategy.


The clinical use of flow cytometry for assessing platelet activation in acute coronary syndromes. TIMI-III Thrombosis and Anticoagulation Group.
Unstable angina signals a sudden transition from stable to unstable atherosclerotic coronary artery disease. Although assessment of platelet activity has been shown to provide diagnostic and prognostic information, most available methods lack sufficient sensitivity or specificity for them to be useful in clinical practice. In recent years, fluorescently labeled antibodies and flow cytometry have permitted the detection of activation proteins on individual platelets. The purpose of the present study was to assess the ability of flow cytometry to detect platelet activation in patients with unstable angina and non-Q-wave myocardial infarction. Platelet activation before treatment was determined from whole-blood samples in 19 patients participating in the Thrombolysis in Myocardial Ischemia (TIMI)-IIIB study and in nine healthy volunteers (total of 24 samples) using flow cytometry and a monoclonal antibody (clone 1E3) to the activation-dependent, surface-expressed protein P-Selectin. Among healthy volunteers, a small percentage of platelets were activated (2.0 +/- 2.5%). In contrast, 15 out of 19 (79%) patients with suspected myocardial ischemia at rest had 10.4 +/- 11.1% activated platelets (95% confidence interval 4.9-15.9%; P < 0.01). Seven patients (37%) were found to have more than 10% activated platelets. The degree of platelet activation did not differ significantly between patients with unstable angina and those with elevated creatine kinase levels (non-Q-wave myocardial infarction). Whole-blood flow cytometric techniques can minimize the artifactual platelet activation often seen with other techniques and therefore offer distinct advantages in the investigation of patients with thrombotic coronary syndromes. In TIMI-III, patients with unstable angina and non-Q-wave myocardial infarction had clear evidence of platelet activation. An ongoing study will examine the correlation between platelet activation assessed using flow cytometry and clinical events in a larger patient cohort.


In Vitro Effects of Ivermectin and Sulphadiazine on Toxoplasma gondii.
Ivermectin and sulphadiazine were tested individually to determine their in vitro effects on Toxoplasma gondii grown in human epidermoid larynx carcinoma (Hep-2) cell culture. In-vitro study. Toxoplasma growth was quantities by an enzyme immunoassay performed directly on the fixed cultures, using a rabbit anti-T. gondii immunoglobulin G as the first antibody and a phosphatase-labeled anti-rabbit immunoglobulin G as the second antibody. For each drug, regression models were used to quantify the relationship between optical density values and antimicrobial agent concentrations in the cultures. The 50% inhibitory concentrations (IC50) of ivermectin and sulphadiazine were found to be 0.2 μg/mL and 7.3 μg/mL after 48 h of exposure, respectively. None of the concentrations tested for each drugs demonstrated toxicity to Hep-2 cells after 72 h of incubation. These results indicate that ivermectin significantly inhibited replication of the tachyzoites of T. gondii RH strain.


Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation.
Aging is associated with decreased skeletal muscle mass and function. These changes are thought to derive, in part, from a reduction in skeletal muscle protein synthesis. Although some studies have shown reduced postabsorptive muscle protein synthesis with age in humans, recent studies have failed to find an age effect. In addition to this disparity, few studies have attempted to characterize the hormonal factors that may contribute to changes in protein synthesis. Thus we examined the effect of age on skeletal muscle protein metabolism, with a specific emphasis on myosin heavy chain (MHC) protein, and the relationship of protein synthesis rates to plasma hormone levels. We measured body composition, muscle function, muscle protein synthesis, MHC and actin protein content, MHC isoform distribution, and plasma concentrations of cytokines and insulin-like growth factor-I (IGF-I) in 7 young [29 +/- 2 (SE) yr] and 15 old (72 +/- 1 yr; P < 0.01) volunteers. Mixed-muscle (-19%; P = 0.11), MHC (-22%; P = 0.08), and nonmyofibrillar (-17%; P = 0.10) protein synthesis all tended to be lower in old volunteers. Old volunteers were characterized by increased circulating tumor necrosis factor-alpha receptor II (P < 0.05) and reduced IGF-I (P < 0.01). In addition, plasma C-reactive protein, interleukin-6, and tumor necrosis factor-alpha receptor II concentrations were negatively related to mixed-muscle and MHC protein synthesis rates (range of r values: -0.422 to -0.606; P < 0.05 to <0.01). No differences in MHC or actin protein content were found. Old volunteers showed reduced (P < 0.05) MHC IIx content compared with young volunteers but no differences in MHC I or IIa. Our data show strong trends toward reduced postabsorptive muscle protein synthesis with age. Moreover, reduced muscle protein synthesis rates were related to increased circulating concentrations of several markers of immune activation.


An in vitro assessment of circumferential grooves on the retention of cement-retained implant-supported crowns.
Crowns cemented on short implant abutments may have insufficient retention. The purpose of this study was to evaluate the effect of circumferential grooves on the retention of cemented cast copings on implant abutments. Sixty similarly-shaped implant abutments were divided into 4 groups (n=15): without grooves, with 1 groove, with 2 grooves, and with 3 grooves. Fifteen identical NiCr cast copings were prepared to fit all 60 abutments. The castings were cemented to each group of abutments with a noneugenol provisional cement (Tempbond NE) and a zinc phosphate cement (Harvard). After thermal cycling and storage for 6 days in a water bath, retention tests were conducted with a tensile testing machine (Instron) (5 mm/min) and retentive forces were recorded. Data were subjected to 1 way-ANOVA, Tukey's (HSD) test, and repeated measures ANOVA (α=.05). For the noneugenol temporary cement, group retention values were increased according to the number of grooves (P<.001). For the zinc phosphate cement, the first groove increased the retention by approximately 60% (P<.001). The retentive values were higher for the zinc phosphate cement than the provisional cement. The influence of the grooves depended on the type of cement used (P<.001). Cement remnants were found primarily on the castings for provisional cement and for the plain abutments cemented with zinc phosphate cement. Remnants were found primarily on the abutments for the grooved abutments cemented with zinc phosphate cement. The addition of circumferential grooves to implant abutments increased the retention of cement-retained castings. For zinc phosphate cement, 1 groove was as effective as several, whereas for the provisional cement, the retention increased gradually with additional grooves.


Gender-Specific Differences in Signs and Symptoms of Dry Eye Disease.
Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film. Epidemiological studies suggest it occurs more frequently in women than men. The aim of this retrospective analysis was to determine whether patients with DED show gender-specific differences in symptoms and signs. A retrospective analysis of 107 patients was conducted at the Department of Ophthalmology of the University of Düsseldorf - Germany. After completing the OSDI questionnaire, the patients underwent objective refraction and were asked about the following symptoms: burning, itching, foreign body sensation, epiphora, sticky eyes, pain, red eyes and swollen eyelids. Furthermore, they underwent an evaluation of the following signs: lipid layer thickness, non-invasive break-up-time (NI-BUT), conjunctival hyperemia, lid parallel conjunctival folds, meibography, Schirmer test and tear meniscus height, ocular surface staining, expressibility of meibomian glands. Of the 107 patients (56.2 ± 17.3 years) 75 were women and 32 men. Women reported significantly more often eyelid swelling (p = .03) and showed a tendency to complain more about red eyes (p = .051), while men tended to complain more often about epiphora (p = .053). In an age-matched sample taken from the cohort, significant differences were found for OSDI-scores (p = .025) showing women reporting more symptoms compared to men, while men showed more conjunctival hyperaemia (p = .004) than women. Women showed a significant thicker lipid layer (p = .0009) in the full cohort, but not in the age-matched sample (p = .43). Although the majority of the investigated parameters did not show gender-specific differences, women reported higher OSDI scores. These findings could be explained by an increased frequency of neuropathic symptoms or ocular surface sensitivity in women or higher resilience of men to consult an ophthalmologist. Sex may have an effect on the clinical characteristics of DED, but further studies are needed to confirm these findings.


Portal vein thrombosis in cirrhotic patients - it is always the small pieces that make the big picture.
Portal vein thrombosis (PVT) is a frequent and serious complication in patients with liver cirrhosis (LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease (compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex end-points such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.


[The potential hazard of the late toxic effects of the new Soviet herbicide levanil and of the semiproducts of its industrial manufacture].
Results of experimental studies in the gonado- and embryotoxicity and teratogenicity of the herbicide levanil (a chlorine derivative of phenoxipropion acid) and its synthetic semiproducts (AXBT, DXBT, OFPK) proved potential embryotoxicity and teratogenic hazards of the AXBT and DXBT semiproducts. The gonadotoxic effects of levanil and its semiproducts were also established. The compounds were characterized by a considerable degree of tropism to gonads. The revealed effects necessitate preventive measures in levanil processing and usage.


Personal versus telephone surveys for collecting household health data at the local level.
Personal and telephone interview surveys were conducted simultaneously during 1981 in the same area (four counties in the area of Tampa Bay, Florida) and utilizing the same interview schedule. Following completion of the surveys, validity checks were made with the medical providers reported by a subsample of respondents to each mode. The telephone survey yielded a lower response rate but cost less than half the personal interview. There was some evidence of nonresponse bias in the telephone survey, and some relatively minor differences in responses were found between the two modes, but there was no conclusive evidence that the response differences resulted from mode effects. Telephone respondents appeared to be somewhat more accurate in their reporting of visits to medical providers, although accuracy comparisons must be interpreted with caution in view of the disparate success experienced for the two modes in securing permission forms for the release of medical record information.


Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs.
Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans.


Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms.
Megakaryocyte expansion in myeloproliferative neoplasms (MPNs) is due to uncontrolled proliferation accompanied by dysregulation of proapoptotic and antiapoptotic mechanisms. Here we have investigated the intrinsic and extrinsic apoptotic pathways of megakaryocytes in human MPNs to further define the mechanisms involved. The megakaryocytic expression of proapoptotic caspase-8, caspase-9, Diablo, p53 and antiapoptotic survivin proteins was investigated in bone marrow specimens of the MPNs (n=145) and controls (n=15) using immunohistochemistry. The megakaryocyte percentage positivity was assessed by light microscopy and correlated with the MPN entity, JAK2V617F/CALR mutation status and platelet count. The proportion of megakaryocytes in the MPNs expressing caspase-8, caspase-9, Diablo, survivin and p53 was significantly greater than controls. A greater proportion of myeloproliferative megakaryocytes expressed survivin relative to its reciprocal inhibitor, Diablo. Differences were seen between myelofibrosis, polycythaemia vera and essential thrombocythaemia for caspase-9 and p53. CALR-mutated cases had greater megakaryocyte p53 positivity compared to those with the JAK2V617F mutation. Proapoptotic caspase-9 expression showed a positive correlation with platelet count, which was most marked in myelofibrosis and CALR-mutated cases. Disruptions targeting the intrinsic apoptotic cascade promote megakaryocyte hyperplasia and thrombocytosis in the MPNs. There is progressive dysfunction of apoptosis as evidenced by the marked reduction in proapoptotic caspase-9 and accumulation of p53 in myelofibrosis. The dysfunction of caspase-9, which is necessary for proplatelet formation, may be the mechanism for the excess thrombocytosis associated with CALR mutations. Survivin seems to be the key protein mediating the megakaryocyte survival signature in the MPNs and is a potential therapeutic target.


A narrative review of the use of a cutting-edge virtual reality rehabilitation technology in neurological and neuropsychological rehabilitation.
Virtual reality (VR) interventions have been increasingly used in the rehabilitation of a wide range of neurological and neuropsychological dysfunctions. Findings of previous reviews showed positive and promising effects of VR-based interventions. However, they summarized findings on VR-based intervention carried out through different VR systems and tasks. We carried out a narrative review with the aim of qualitatively synthesising the results of previous studies that used specific VR systems, i.e. the Khymeia -Virtual Reality Rehabilitation System, for treatment purposes. We searched the literature in various databases (i.e. EMBASE, Web of Science, SCOPUS, PubMed and PubMed Central) for studies published until November 23, 2023. 30 studies were selected. The VRRS was used for neuromotor rehabilitation only in 13 studies, for cognitive rehabilitation in 11 studies, and for both neuromotor and cognitive rehabilitation in six studies. The study design was heterogeneous including 15 randomised controlled trials. After discussing each study according to the type of rehabilitation we concluded that the use and efficacy of VRRS rehabilitative intervention for increasing the neurological and neuropsychological functioning of patients are promising but more evidence is needed to make a comparison with conventional treatment. Future studies should also include long-term follow-up as well as cost-effectiveness analysis.


Liquid Biopsies in Sarcoma Clinical Practice: Where Do We Stand?
Sarcomas are rare tumors of bone and soft tissue with a mesenchymal origin. This uncommon type of cancer is marked by a high heterogeneity, consisting of over 70 subtypes. Because of this broad spectrum, their treatment requires a subtype-specific therapeutic approach. Tissue biopsy is currently the golden standard for sarcoma diagnosis, but it has its limitations. Over the recent years, methods to detect, characterize, and monitor cancer through liquid biopsy have evolved rapidly. The analysis of circulating biomarkers in peripheral blood, such as circulating tumor cells (CTC) or circulating tumor DNA (ctDNA), could provide real-time information on tumor genetics, disease state, and resistance mechanisms. Furthermore, it traces tumor evolution and can assess tumor heterogeneity. Although the first results in sarcomas are encouraging, there are technical challenges that need to be addressed for implementation in clinical practice. Here, we summarize current knowledge about liquid biopsies in sarcomas and elaborate on different strategies to integrate liquid biopsy into sarcoma clinical care.


A cytosolically localized far-red to near-infrared rhodamine-based fluorescent probe for calcium ions.
Ca2+ is one of the most important second messengers in cells. A far-red to near-infrared (NIR) Ca2+ fluorescent probe is useful for multi-color imaging in GFP or YFP-expressing biosamples. Here we developed a cytosolically localized far-red to NIR rhodamine-based fluorescent probe for Ca2+, CaSiR-2 AM, while rhodamine dyes are basically localized to mitochondria or lysosomes in cells.


A Rare Case of Scalp Metastasis from Encapsulated Angioinvasive Follicular Thyroid Carcinoma.
Cutaneous metastases from thyroid carcinomas are extremely rare; however, the scalp is a common site for cutaneous metastases from follicular thyroid carcinomas (FTCs). We report the case of a 77-year-old male patient with a blood-rich scalp lesion. Histopathological tests of punch biopsy specimens revealed subcutaneous well-formed follicular structures that were similar to those found in the thyroid gland. Immunohistochemistry using thyroid transcription factor-1 (TTF-1) and paired-box gene family 8 (PAX8) revealed an FTC metastasis. We performed total thyroidectomy and resection of the scalp lesion at the same time and administered postoperative radioactive iodine treatment. The primary thyroid lesion was diagnosed as an FTC based on extracapsular extension and vessel invasion. The patient has not experienced disease recurrence since the treatment. When scalp metastasis of thyroid carcinoma is suspected, we recommend total extirpation, including the primary tumor and scalp metastasis, for an improved prognosis.


Reduced angiovasculogenic and increased inflammatory profiles of cord blood cells in severe but not mild preeclampsia.
Preeclampsia (PE) is a prevalent pregnancy disorder that leads to high maternal and fetal morbidity and mortality. While defective vascular development and angiogenesis in placenta are known as crucial pathological findings, its pathophysiological mechanism remains elusive. To better understand the effects of PE on angio-vasculogenesis and inflammatory networks in the fetus and to identify their biological signatures, we investigated the quantitative and functional characteristics of cord blood-derived mononuclear cells (CB-MNCs) and CD31-positive MNCs. Flow cytometry analysis demonstrated that the CB-MNCs from the severe PE group had significantly decreased number of cells expressing CD3, CD11b, CD14, CD19, KDR, and CD31 compared with the normal group. Quantitative real time PCR (qRT-PCR) shows down-regulation of the major angiogenic factor VEGFA in MNCs and CD31+ MNCs in severe PE. The major inflammatory cytokines IL1 was highly upregulated in CD31+ CB-MNCs in the severe PE patients. Mild PE patients, however, did not display any significant difference in expression of all measured angiogenic genes and most inflammatory genes. These findings show distinct angiogenic and inflammatory signatures from severe PE, and they may play a significant role in the pathogenesis of vascular defects in placenta of severe PE.


Investigation of ospC Expression Variation among Borrelia burgdorferi Strains.
Outer surface protein C (OspC) is the most studied major virulence factor of Borrelia burgdorferi, the causative agent of Lyme disease. The level of OspC varies dramatically among B. burgdorferi strains when cultured in vitro, but little is known about what causes such variation. It has been proposed that the difference in endogenous plasmid contents among strains contribute to variation in OspC phenotype, as B. burgdorferi contains more than 21 endogenous linear (lp) and circular plasmids (cp), and some of which are prone to be lost. In this study, we analyzed several clones isolated from B. burgdorferi strain 297, one of the most commonly used strains for studying ospC expression. By taking advantage of recently published plasmid sequence of strain 297, we developed a multiplex PCR method specifically for rapid plasmid profiling of B. burgdorferi strain 297. We found that some commonly used 297 clones that were thought having a complete plasmid profile, actually lacked some endogenous plasmids. Importantly, the result showed that the difference in plasmid profiles did not contribute to the ospC expression variation among the clones. Furthermore, we found that B. burgdorferi clones expressed different levels of BosR, which in turn led to different levels of RpoS and subsequently, resulted in OspC level variation among B. burgdorferi strains.


Effect of a weight loss program on body composition and metabolic syndrome markers in obese weight cyclers.
to evaluate the effect of weight loss program on fat mass, visceral fat rating and metabolic syndrome markers in obese subjects with weight cycling. this was an 8-week open trial. The subjects were recruited consecutively from Balai Kota DKI Jaya. Subjects were classified into two groups according to the fluctuation of weight gain (weight cycling/WC and first encounter obesity/FEO group). Both groups were assigned to receive weight loss program consisted with following goals: a 1000 kcal energy intake reduction and 45 minutes mild-to-moderate intensity physical activity three times a week. Body composition (fat mass, visceral fat rating), and metabolic syndrome markers (waist circumference and triglyceride levels) were measured at baseline, week 4 and at the end of study. seventy two subjects completed the study (34 subjects in WC group and 38 subjects in FEO group). Following weight loss program, a decrease in fat mass, visceral fat rating, and waist circumference was lower in WC group compared with FEO group but it was not statistically significant (p>0.05). Triglyceride levels were decreased in the FEO group while it was increased in WC group. However the difference was not significant (p=0.055). weight loss program may contribute to changes in body composition and metabolic syndrome markers in obese subjects, which the response appears to be worse in weight cyclers.


Missing correlation of retinal vessel diameter with high-altitude headache.
The most common altitude-related symptom, high-altitude headache (HAH), has recently been suggested to originate from restricted cerebral venous drainage in the presence of increased inflow caused by hypoxia. In support of this novel hypothesis, retinal venous distension was shown to correlate with the degree of HAH. We quantified for the first time retinal vessel diameter changes at 4559 m using infrared fundus images obtained from a state of the art Spectralis™ HRA+OCT with a semiautomatic VesselMap 1® software. High-altitude exposure resulted in altered arterial and venous diameter changes at high altitude, however, independent of headache burden.


Identification of osmoadaptive strategies in the halophile, heterotrophic ciliate Schmidingerothrix salinarum.
Hypersaline environments pose major challenges to their microbial residents. Microorganisms have to cope with increased osmotic pressure and low water activity and therefore require specific adaptation mechanisms. Although mechanisms have already been thoroughly investigated in the green alga Dunaliella salina and some halophilic yeasts, strategies for osmoadaptation in other protistan groups (especially heterotrophs) are neither as well known nor as deeply investigated as for their prokaryotic counterpart. This is not only due to the recent awareness of the high protistan diversity and ecological relevance in hypersaline systems, but also due to methodological shortcomings. We provide the first experimental study on haloadaptation in heterotrophic microeukaryotes, using the halophilic ciliate Schmidingerothrix salinarum as a model organism. We established three approaches to investigate fundamental adaptation strategies known from prokaryotes. First, proton nuclear magnetic resonance (1H-NMR) spectroscopy was used for the detection, identification, and quantification of intracellular compatible solutes. Second, ion-imaging with cation-specific fluorescent dyes was employed to analyze changes in the relative ion concentrations in intact cells. Third, the effect of salt concentrations on the catalytic performance of S. salinarum malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) was determined. 1H-NMR spectroscopy identified glycine betaine (GB) and ectoine (Ect) as the main compatible solutes in S. salinarum. Moreover, a significant positive correlation of intracellular GB and Ect concentrations and external salinity was observed. The addition of exogenous GB, Ect, and choline (Ch) stimulated the cell growth notably, indicating that S. salinarum accumulates the solutes from the external medium. Addition of external 13C2-Ch resulted in conversion to 13C2-GB, indicating biosynthesis of GB from Ch. An increase of external salinity up to 21% did not result in an increase in cytoplasmic sodium concentration in S. salinarum. This, together with the decrease in the catalytic activities of MDH and ICDH at high salt concentration, demonstrates that S. salinarum employs the salt-out strategy for haloadaptation.


[Ensuring the sanitary and epidemiological safety of the child population in Russia].
The summarizing data on new negative tendencies in the state of health of children and adolescents in Russia are presented. The two-fold increased proportion of children with chronic pathology and disability is noted. Special attention is drawn to a high level of child morbidity in diseases of respiratory organs, especially bronchial asthma. Measures ensuring the sanitary and hygienic safety of the child population in Russia, including improvements in the organization of nourishment, vaccinal prophylaxis, working out hygienic criteria and health-saving technologies, have been analyzed. Priorities in the work aimed at the liquidation of negative tendencies in the health of the child population in Russia have been determined.


The effects of intra-articular methylprednisolone and exercise on the mechanical properties of articular cartilage in the horse.
Intra-articular corticosteroids are widely used as anti-inflammatory agents for symptomatic management of arthritis, but their administration with concurrent exercise remains controversial. Biochemical and morphologic analysis of treated cartilage has revealed conflicting results, but previous biomechanical assessment has not been undertaken. To compare the biomechanical properties of intra-articular methylprednisolone acetate (MPA) and diluent treated cartilage in treadmill exercised horses. Eight 2-year-old female horses had MPA or diluent administered into contralateral middle carpal joints at 14 day intervals for a total of four treatments per horse. Horses underwent a standard treadmill exercise protocol until euthanasia (day 70). Standard sites were tested on the third, radial and intermediate carpal bones using an automated indentation apparatus to obtain the creep and recovery behavior of the articular cartilage. Using previously validated biphasic creep indentation methodology, aggregate modulus, Poisson's ratio, permeability, shear modulus, thickness, creep and recovery equilibrium times and percent recovery were obtained at each site. Results were analyzed using ANOVA and multiple comparisons of the means (P < 0.05). Cartilage intrinsic material properties and thickness demonstrated significant differences between MPA and diluent treated joints. Diluent treated cartilage had a 97% increase in compressive stiffness modulus (P = 0.0001), was 121% more permeable (P = 0.0001), had 88% increase in shear modulus (P = 0.0001), and was 24% thicker (P = 0.0001) than MPA treated articular cartilage. The findings indicate that repetitive intra-articular administration of MPA to exercising horses alters the mechanical integrity of articular cartilage, which could lead to early cartilage degeneration.