Toward a prophylaxis against fetal and neonatal alloimmune thrombocytopenia: induction of antibody-mediated immune suppression and prevention of severe clinical complications in a murine model.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal or neonatal platelets (PLTs). Results from our recent large screening study suggest that the pathophysiology of FNAIT is more similar to hemolytic disease of the fetus and newborn (HDFN) than previously thought. Immunization against HPA-1a might therefore be preventable by a prophylactic regimen of inducing antibody-mediated immune suppression (AMIS), which has been documented to be a useful prophylaxis against HDFN. This preclinical proof-of-concept study investigated whether passive administration of anti-β3 integrin could induce AMIS and thereby prevent clinical complications of FNAIT. A murine model of FNAIT using β3 integrin (GPIIIa)-deficient (β3-/-) mice was employed for this study. AMIS in β3-/- mice was induced by intravenous administration of human anti-HPA-1a immunoglobulin G or murine anti-β3 antisera given as prophylaxis after transfusion of HPA-1a-positive human PLTs or murine wild-type PLTs, respectively. AMIS against both human and murine PLT antigens was induced using this prophylactic approach, reducing the amount of maternal PLT antibodies by up to 90%. Neonatal PLT counts were significantly increased and pregnancy outcome was improved in a dose-dependent manner. The incidence of intracranial hemorrhage, miscarriage, and dead-born pups in mice receiving high-dose prophylaxis was reduced to that of normal controls. We also observed that the severity of thrombocytopenia inversely correlated with birth weight. This work conceptually proves that prophylactic administration of PLT antibodies induces AMIS and prevents poor pregnancy outcome in FNAIT.


Cell detachment: post-isolation challenges.
Rare cells already have become established indicators for disease diagnosis, to help track prognosis, and in developing personalized therapy. Numerous techniques have been developed to effectively and specifically detect and sort rare cells and cell isolation techniques have gained much attention among researchers in the last few decades. Recent developments in nanotechnologies and microfluidics have been used with great promise towards these goals. The research emphasis has also shifted from simple detection with microfluidic devices to comprehensive isolation, collection and subsequent analysis with integrated and automated systems. The first challenge in post-isolation analysis is cell detachment from substrates, while keeping cells viable and unperturbed. In this review, various methods used for cell detachments are discussed. For effective cell sorting, the detachment is identified as critical criteria for selecting substrates and methods.


Impaired glucose absorption in children with severe malnutrition.
To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.


Pancytopenia in a patient with cystinosis secondary to myelosuppression from cystine crystal deposition: a case report.
Cystinosis is a rare metabolic genetic disorder caused by a mutation in the cystinosin lysosomal cystine transporter gene. Clinically, it is characterized by systemic accumulation of cystine crystals in tissues causing end-organ dysfunction in the kidney, eyes, muscles, and other organs in the body. In very rare cases, it can also involve the bone marrow and the resulting cystine crystal deposition can cause myelosuppression leading to pancytopenia. Here we report the case of a 26-year-old white woman with cystinosis and other complex medical comorbidities who developed pancytopenia. She was worked up extensively and ruled out for common causes of pancytopenia (infectious disorders, vitamin deficiencies secondary to gastrointestinal malabsorption, rheumatologic, and hematologic disorders). On bone marrow biopsy she was found to have extensive deposits of cystine crystals, which was thought to be the cause of her myelosuppression leading to her pancytopenia. As a result, by treating her underlying cystinosis more aggressively we were able to observe an improvement in her pancytopenia a few months afterwards. Pancytopenia secondary to myelosuppression from cystine crystal deposition in the bone marrow is a very rare complication that has been reported in only a handful of case reports. This case illustrates the importance of keeping a broad differential diagnosis and systematically ruling out common causes of pancytopenia. It also demonstrates the importance of bone marrow biopsies in the evaluation of unexplained pancytopenia.


Antimicrobial and Cytotoxic Activity of Ocimum tenuiflorum and Stevia rebaudiana-Mediated Silver Nanoparticles - An In vitro Study.
Silver nanoparticles (AgNPs) are the nanoparticles of silver between 1 nm and 100 nm in size. In this study, AgNPs were extracted from Ocimum tenuiflorum and Stevia rebaudiana which is a medicinal plant of Indian origin, worshipped by the Hindus and used in Ayurvedic medicine since ancient times. The aim of the study was to assess the antimicrobial and cytotoxic effect of AgNPs reinforced with the herb O. tenuiflorum and S. rebaudiana against oral pathogens. In this in vitro study, the organisms used were Streptococcus mutans, Staphylococcus aureus, Lactobacillus sp., and Candida albicans. Agar well-diffusion method was used to assess the antimicrobial efficacy of the nanoparticles at 25 mL, 50 mL, and 100 mL. To assess the cytotoxic effect, brine shrimp lethality assay was used. Zone of inhibition was found to be highest at 100 mL against S. mutans, S. aureus, Lactobacillus sp., and C. albicans. The cytotoxic activity at 5 mL and 10 mL was 0%. The maximum cytotoxicity was seen at 80 mL where 30% of the Nauplii's died. The findings from this study suggest that AgNPs reinforced with O. tenuiflorum and S. rebaudiana extracts has the potential as an antimicrobial agent and has less cytotoxic effect on brime shrimp and can be used as an alternative to commercially available antimicrobial agents.


The persistent influence of concussion on attention, executive control and neuroelectric function in preadolescent children.
The aim of this investigation was to examine the influence of pediatric sport-related concussion on brain and cognitive function. To do so, we used a between-participants design, measures of executive control, and event-related potentials (ERPs). The findings demonstrate that children with a history of concussion exhibit behavioral deficits in attention, working memory and impulse control, as well as neuroelectric alterations in ERP indices of visual attention (N1), conflict resolution (N2) and attentional resource allocation (P3). Furthermore, the age at injury related to the magnitude of several concussion-related deficits. Accordingly, a single sports-related concussive incident during childhood (m=2.1years prior to testing) may lead to subtle, yet pervasive alterations in the behavioral and neural indices of attention and executive control, and age at injury may moderate injury outcomes.


Dietary trans fatty acids and risk of colorectal cancer: a systematic review and meta-analysis of observational studies.
Although trans fatty acid has been associated with diabetes and cardiovascular disorders, studies gave conflicting results when examined their impact on colorectal cancer (CRC). The present systematic review and meta-analysis aimed to summarize the current evidence regarding the association between dietary and tissue trans fatty acids and the risk of CRC. We searched PubMed/MEDLINE, EMBASE, Scopus, Web of Science (ISI), and Google Scholar without date and language limitation up to May 2022 and included the eligible studies. The quality of included studies was assessed using the Newcastle-Ottawa scale. The overall odds ratios (ORs) were derived using a random-effects model. In assessment of dietary trans fatty acids 18 studies, including eight cohort, 10 case-control, and observational data from one randomized control trial were included. Although Dietary trans fats were associated with higher risk of CRC (OR = 1.093, 95% CI 1.017, 1.176, P = 0.016; I2 = 61.3%), Subgroup analysis by study design yielded an insignificant effect for case-control (OR = 1.152, 95% CI 1.000, 1.328, P = 0.050; I2 = 77.2%) and cohort (OR = 1.027, 95% CI 0.976, 1.081, P = 0.299; I2 = 0%) studies. Although there was no significant association of trans fatty acids with rectal cancer (OR = 1.093, 95% CI 0.984 to 1.215, P = 0.098; I2 = 0%), there was for colon cancer (OR = 1.91, 95% CI 1.062 to 1.335, P = 0.003; I2 = 37.6%).The analysis of four studies that evaluated the relation between tissue trans fat and CRC revealed meaningful result (OR = 0.745, 95% CI 0.619, 0.896, P = 0.002; I2 = 42.6%). While subgroup assessments for colon cancer (OR = 0.804, 95% CI 0.583, 1.109, P = 0.183; I2 = 0%) and plasma trans fatty acids OR = 0.853, 95% CI 0.633, 1.150, P = 0.298; I2 = 0%) were insignificant. Dietary trans fatty acids increased the risk of CRC, whereas tissue trans fatty acids had a protective effect on CRC. Nonetheless, neither type of trans fatty acid increased the risk of colon or rectal cancer; thus, more prospective studies are needed to determine the validity of these associations.


[Perforated gastric and duodenal ulcers; results of treatment by probit analysis (author's transl)].
The results of treatment of perforated gastric and duodenal ulcers given in death rates are checked critically. Analagous to burn injuries probit analysis gives more evidence in this field.


Efficacy of water- and oil-in-water-formulated Metarhizium anisopliae in Rhipicephalus sanguineus eggs and eclosing larvae.
Conidia of the entomopathogenic fungus Metarhizium anisopliae (Ascomycota: Clavicipitaceae) were assessed against Rhipicephalus sanguineus (Arachnida: Ixodidae) eggs under laboratory conditions. Clusters of 25 eggs were applied either directly with the fungal conidial formulations or set on previously fungus-treated filter paper. Treatments consisted of conidia formulated in water or an oil-in-water emulsion at final concentrations of 3.3 × 10(3), 10(4), 3.3 × 10(4), 10(5), or 3.3 × 10(5) conidia/cm(2). The development of mycelium and new conidia on egg clusters incubated at 25 °C and humidity close to saturation depended on conidial concentration, formulation, and application technique. No larvae eclosed from eggs after direct applications of conidia regardless of the formulation. The eclosion and survival of larvae from indirectly treated egg clusters depended on the type of formulation and conidial concentration applied. Oil-in-water formulations of conidia demonstrated the highest activity against eggs of R. sanguineus.


Effects of growth hormone on cognitive, motor, and behavioral development in Prader-Willi syndrome children: a meta-analysis of randomized controlled trials.
The benefits of growth hormone (GH) therapy in Prader-Willi syndrome (PWS) children are well established, but there is still considerable controversy regarding whether GH treatment can improve cognitive, motor, and behavioral development in PWS children. The objectives of this meta-analysis were to quantitatively evaluate the effects of GH on cognitive, motor function, and behavioral development in PWS children. Randomized controlled trials (RCTs) examining the effects of GH on cognitive, motor, and behavioral development in PWS children were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases. Intervention effects were represented by Hedges'g and pooled to calculate effect sizes using a random-effects model. Ten relevant studies comprising data from 302 participants were finally included. We observed no significant difference in cognitive performance between the GH treatment group and the control group (p = 0.197). GH treatment was shown to remarkably improve motor development in PWS children compared with the control treatment (p < 0.001), with moderate positive treatment effects (Hedges'g [95% CI] = 0.71 [0.38, 1.03]). There were no significant differences between the GH group and the control group based on objective assessments of behavioral development (p = 0.53). The meta-analysis suggested that GH treatment had a significantly positive effect on motor development, with moderate treatment effects in PWS children; however, there was no evidence of effects on cognitive or behavioral development.


Amantadine intoxication despite moderate renal dysfunction: A case of combined use with donepezil.
Amantadine intoxication occurred despite moderate renal dysfunction. This may have been affected by the use of donepezil, and we require careful attention to these combinations.


Serum cholinesterase is associated with incident diabetic retinopathy: the Shanghai Nicheng cohort study.
Serum cholinesterase (ChE) is positively associated with incident diabetes and dyslipidemia. We aimed to investigate the relationship between ChE and the incidence of diabetic retinopathy (DR). Based on a community-based cohort study followed for 4.6 years, 1133 participants aged 55-70 years with diabetes were analyzed. Fundus photographs were taken for each eye at both baseline and follow-up investigations. The presence and severity of DR were categorized into no DR, mild non-proliferative DR (NPDR), and referable DR (moderate NPDR or worse). Binary and multinomial logistic regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) between ChE and DR. Among the 1133 participants, 72 (6.4%) cases of DR occurred. The multivariable binary logistic regression showed that the highest tertile of ChE (≥ 422 U/L) was associated with a 2.01-fold higher risk of incident DR (RR 2.01, 95%CI 1.01-4.00; P for trend < 0.05) than the lowest tertile (< 354 U/L). The multivariable binary and multinomial logistic regression showed that the risk of DR increased by 41% (RR 1.41, 95%CI 1.05-1.90), and the risk of incident referable DR was almost 2-fold higher than no DR (RR 1.99, 95%CI 1.24-3.18) with per 1-SD increase of loge-transformed ChE. Furthermore, multiplicative interactions were found between ChE and elderly participants (aged 60 and older; P for interaction = 0.003) and men (P for interaction = 0.044) on the risk of DR. In this study, ChE was associated with the incidence of DR, especially referable DR. ChE was a potential biomarker for predicting the incident DR.


The association between fast-food consumption and job-related factors among Russian adults.
Time constraints contribute to individuals' dietary choices along with incomes, prices, and preferences. As fast food is prepared and served quickly, it is often preferred to other food options, especially when individuals are under time pressure. This paper focuses on a set of job-related characteristics that could potentially contribute to fast-food consumption choice, and controls for standard socio-demographic, economic, and lifestyle factors. This study uses data from a quantitative household survey on health behavior and medicine of Russian adults conducted in 2017 (n = 4006). The study applies simple probit, ordered probit, and zero-inflated ordered probit models to examine how job-related characteristics are connected to the probability and frequency of fast-food consumption among Russian adults. The results shows that employment is positively associated with both probability and frequency of fast-food consumption. However, for working adults, the decisions to eat fast food, and how frequently it is eaten, are affected by different factors. For example, working part time decreases the probability of fast-food consumption; having more than one job increases the frequency of its intake for fast-food consumers; having canteens with hot meals at work decreases the frequency of fast-food intake. Although job-related factors are significant in all models, marginal effects show that living in large cities, especially Moscow and Saint Petersburg, plays a larger role in the probability and frequency of fast-food consumption because access to various fast-food outlets increases in relation to the size of the settlement.


A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer.
A prospective randomised trial was undertaken to evaluate the role of neoadjuvant chemoendocrine therapy prior to surgery in primary operable breast cancer. Three hundred nine women (median age 56 years, range 27-70) with primary operable breast cancer confirmed on fine needle aspiration (FNA) cytology were recruited to this study. They were treated with a combination of mitozantrone and methotrexate (+/- mitomycin-C) combined with tamoxifen (2MT). Patients received eight cycles of 2MT (four prior to surgery in the neoadjuvant group) and tamoxifen for five years with appropriate surgery and radiotherapy. The two groups were comparable for age, menopausal status, stage and surgical requirements. The clinical response rates to neoadjuvant therapy were as follows: 22% complete response (CR), 29% minimal residual disease (MRD), 33% partial response (PR), 15% no change (NC) and only two patients had clinical evidence of progressive disease. Surgical requirements were reduced from 31 patients (22%) of the adjuvant group having mastectomy to 14 (10%) in the neoadjuvant group (P < 0.003). At a median follow-up of 48 months (range 10-70 months) there is no statistically significant difference between the two groups in terms of local relapse, metastatic relapse or overall survival. Symptomatic and haematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. This randomised trial has shown a significant reduction in the surgical requirements for mastectomy, after treatment with neoadjuvant chemoendocrine therapy, with no deterioration in local or distal relapse.


Human intervertebral disc: structure and function.
This review begins with a brief introduction in which the development, blood supply and innervation of the intervertebral disc is considered, particularly as these may influence the following sections on structure and function. The three regions within the disc--that is, the nucleus pulposus, annulus fibrosus, and cartilage end plates--are considered in some detail. There appears to be no distinct border between the central nucleus pulposus and the outer annulus fibrosus, the main difference being in their fibrous structure. The fluid space is important in the nutrition of the disc, showing plastic deformation and recovery characteristics. The structural elements, both macroscopically and microscopically, together with the biochemical elements, are intimately related to function. The intervertebral disc should not be though of as a homogeneous and static structure; it has a heterogeneous composition and responds dynamically to applied loads. Neither should it be considered as an isolated structure because it interacts with the vertebral bodies, together constituting the vertebral unit. Furthermore, changes within the disc can, and do, have dramatic effects on vertebral column kinematics. The intervertebral disc is not inactive; it is capable of self-maintenance; in injury it can repair itself and has considerable regenerative properties.


Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs.
Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen.


Old and new prognostic factors in acute myeloid leukemia with deranged core-binding factor beta.
Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50-70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. Increasing age was the only predictor for survival (P <0.001), with an optimal cut-point at 43 years. White blood cells (WBCs) at diagnosis emerged as an independent risk factor for relapse incidence (P = 0.017), with 1.1% increase of hazard for each 1.0 × 10(9) /L WBC increment. KIT mutations lacked prognostic value for survival and showed only a trend for relapse incidence (P = 0.069).


Head and neck presentations of B-NHL and B-AL in children/adolescents: experience of the LMB89 study.
Describe the epidemiology, clinical profiles and outcomes associated with head and neck (H&N) involvement in children/adolescents with B-cell non-Hodgkin lymphoma (B-NHL). Analysis of children/adolescents with H&N B-NHL prospectively enrolled in the SFOP LMB-89 trial (July 1989-June 1996). One hundred and twelve of 561 patients (20%) had H&N involvement. The mean age of the patients was 8.4 years. Murphy staging differed between the H&N patients and the others (P < 0.0001): 9% versus 5% of the patients presented with stage I disease, 36% versus 11% presented with stage II disease, 12% versus 59% presented with stage III disease, 17% versus 10% with stage IV disease and 27% versus 16% with B-AL. Twenty-nine H&N patients (26%) had CNS involvement at diagnosis versus 8.5% in the group without H&N involvement (P < 0.0001). Patients were treated according to the LMB89 protocol: 3 H&N patients were allocated to group A, 70 to group B and 39 to group C. Ninety-seven percent of H&N patients achieved CR and event-free and overall survival at 4 years was 95.5% (5 deaths in patients with CNS disease). On multivariate analysis, EFS was significantly better in H&N patients than in non-H&N patients (P = 0.021), but not OS (P = 0.11). The H&N site is the second most common location for B-NHL at diagnosis and is more frequently associated with disseminated disease and CNS involvement than other sites. However, outcomes are no worse for these patients than for the rest of the population.


An automated, pressure-driven sampling device for harvesting from liquid cultures for genomic and biochemical analyses.
Here we describe an automated, pressure-driven, sampling device for harvesting 10 to 30 ml samples, in replicate, with intervals as short as 10 s. Correlation between biological replicate time courses measured by microarrays was extremely high. The sampler enables sampling at intervals within the range of many important biological processes.


Improved fragment-based protein structure prediction by redesign of search heuristics.
Difficulty in sampling large and complex conformational spaces remains a key limitation in fragment-based de novo prediction of protein structure. Our previous work has shown that even for small-to-medium-sized proteins, some current methods inadequately sample alternative structures. We have developed two new conformational sampling techniques, one employing a bilevel optimisation framework and the other employing iterated local search. We combine strategies of forced structural perturbation (where some fragment insertions are accepted regardless of their impact on scores) and greedy local optimisation, allowing greater exploration of the available conformational space. Comparisons against the Rosetta Abinitio method indicate that our protocols more frequently generate native-like predictions for many targets, even following the low-resolution phase, using a given set of fragment libraries. By contrasting results across two different fragment sets, we show that our methods are able to better take advantage of high-quality fragments. These improvements can also translate into more reliable identification of near-native structures in a simple clustering-based model selection procedure. We show that when fragment libraries are sufficiently well-constructed, improved breadth of exploration within runs improves prediction accuracy. Our results also suggest that in benchmarking scenarios, a total exclusion of fragments drawn from homologous templates can make performance differences between methods appear less pronounced.


Suppression of programmed cell death by intracellular cAMP is not mediated by expression of genes encoding an inhibitor of apoptosis.
The elevation of intracellular cAMP content is accompanied by expression of genes whose promoter contains a Ca(2+)-cAMP responsive element. In vascular smooth muscle cells (VSMC), activation of cAMP signaling blocks apoptosis triggered by serum deprivation. In the present study we investigated the role of gene expression in the inhibition of apoptosis by cAMP. In VSMC transfected with E1A adenovirus, incubation in the absence of serum for 6 h led to 20-fold elevation of chromatin fragmentation and 10-fold activation of caspase-3 activity, these being employed as markers of apoptosis. Forskolin-induced activation of cAMP signaling was accompanied by 50% elevation of RNA synthesis and completely abolished the development of apoptosis during the initial 6 h incubation in growth factor-free medium. In 12 h apoptosis in forskolin-treated VSMC was slowly developed and after 24 h the content of chromatin fragments was 2-fold less than in control cells. Addition of actinomycin D and cycloheximide completely blocked RNA synthesis and decreased protein synthesis by 80%, respectively. Neither compound affected baseline apoptosis or its inhibition by forskolin. More than 70 newly phosphorylated proteins were observed by 2D-electrophoresis of VSMC after incubation with forskolin for 3 h; in 24 h the number of phosphoproteins triggered by forskolin was decreased by 2-3-fold. These results show that suppression of VSMC apoptosis under activation of cAMP signaling is mediated via posttranslational modification of pre-existing intermediates of the apoptotic machinery rather than by de novo synthesis of inhibitors of programmed cell death.


Interaction of nystatin with nystatin-resistant Candida tropicalis.
Nystatin-resistant yeast Candida tropicalis was obtained after UV illumination and plating on nystatin-containing media. The mutant contained no ergosterol in the plasma membrane but bound nystatin to a degree similar to that of the wild strain (1.2 vs. 1.5 nmol per mg dry solid). Respiration of the mutant on glucose was reduced by 36% in the presence of 25 microM nystatin. This corresponded to a 25-43% decrease of the uptake of monosaccharides. Transport of amino acids was reduced by nystatin in the mutant by 44-86%, as compared with a 84-95% reduction in the wild strain. The intracellular ATP content was reduced by nystatin equally in the wild strain and in the mutant (by 43 and 47%). Nystatin appears to affect specifically membrane transport processes of nonelectrolytes while both the H+-extruding ATPase and the membrane potential are unaffected.


The vicious circle between homocysteine, methyl group-donating vitamins and chronic levodopa intake in Parkinson's disease.
A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generating mechanisms in levodopa-treated patients with Parkinson's disease. We conclude to recommend levodopa-treated patients to substitute themselves with methyl group-donating vitamins. This is harmless in terms of application of folic acid, methylcobalamin or hydroxocobalamin. Moreover, we suggest a crucial discussion on the value of the various popular hypotheses on Parkinson's disease-generating mechanisms. Findings from studies with acute levodopa exposure describe oxidative stress generation and impaired methylation capacity, which causes gene dysfunction. Their repeated occurrences contribute to onset of mitochondrial dysfunction, iron enrichment and pathologic protein accumulation in the long term. Current research underestimates these epigenetic, metabolic consequences of chronic levodopa application. Supplementary treatment strategies are recommended to avoid levodopa-related side effects.


What supports effective research links between Divisions of General Practice and universities?
To find out what supports effective links between Divisions of General Practice and universities. Qualitative study based on semi-structured interviews during October 2004, from which a framework for effective linking was constructed and its validity assessed by discussion with researchers and Division staff and members at four interactive workshops held between 9 November 2004 and 5 November 2005 . 21 participants from Divisions of General Practice and universities in Australia. Qualities conceptualised as "opportunity" and "fair relationships" were critical factors in establishing successful links between the two sectors. The relationship between these two factors describes the types of interactions that currently occur. To develop effective links requires an environment that promotes adequate opportunities, and in which mutual trust can grow. This will require commitment and system change from all parties.


Excessive supraventricular ectopic activity and future onset of atrial fibrillation in patients with cryptogenic stroke.
Although evidence has shown the association of excessive supraventricular ectopic activity (ESVEA) with future development of atrial fibrillation (AF), this relationship is not yet fully understood. This study examines whether ESVEA can predict the future onset of AF, in patients presenting with cryptogenic stroke. A retrospective cohort of 124 non-AF, consecutive patients, hospitalized for cryptogenic stroke between 2014 and 2015, was retrieved. 24-h inpatient monitoring with Holter was employed to reveal ESVEA, defined as the presence of more than 20 premature atrial complexes per hour (PACs/h) on average, or a more than 5 s duration of the longest supraventricular run (LSVR). After a median follow-up period of 5.2 years, the patients were examined for AF. From initial 124 patients, 12 died and one was lost during follow-up. For the total of 111 patients finally included, the median age was 56 years and 25.2% were females. The overall baseline median CHA2DS2-VASc score was 3. AF was found in 13 (11.71%) patients. Patients who were finally diagnosed with AF had a significantly higher number of PACs/h and a longer median LSVR duration at baseline (16.67 vs. 0.21, p < 0.001 and 3 vs. 0 s, p < 0.001, respectively). The presence of ESVEA was also significantly more frequent among AF patients (46.15%, 95%CI: 17.78%-74.22%) compared to non-AF ones (6.1%, 95%CI: 1.3%-10.7%, p < 0.001). Excessive atrial ectopy, detected with 24 h inpatient Holter monitoring, is a significant indicator of future development of AF in patients presenting originally with a cryptogenic stroke.


Pregnancy outcome following Mustard procedure for transposition of the great arteries: a report of five cases and review of the literature.
To review outcomes and complications of pregnancies in women with transposition of the great arteries who had undergone the Mustard procedure. Four women with transposition of the great arteries who had undergone Mustard procedures in childhood received their obstetric care for five pregnancies at three institutions in the greater Philadelphia area between 1990-1992. Pregnancy complications and outcomes were reviewed. The most common maternal complication in pregnancy following performance of the Mustard procedure was cardiac arrhythmia, which required treatment in two of four patients. Late-onset fetal growth restriction requiring induction occurred in two of five pregnancies. Third-trimester oligohydramnios requiring induction occurred in one patient, and her second pregnancy was complicated by preterm labor and premature rupture of the membranes (PROM) at 33 weeks. One patient with a twin pregnancy developed mild preeclampsia, preterm labor, and PROM at 30 weeks. There were no neonatal or perinatal deaths or significant morbidity. If a patient with transposition of the great arteries who underwent the Mustard procedure is hemodynamically stable before pregnancy, good maternal and fetal outcome can be expected.


Variable, voltage-dependent, blocking effects of nitrendipine, verapamil, diltiazem, cinnarizine and cadmium on adrenomedullary secretion.
1. Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min-1) at 37 degrees C with modified Krebs solutions lacking Ca and containing 1.2 mM K (hyperpolarizing solution) or 118 mM K (depolarizing solution) was triggered by 10-s pulses of Ca (0.5 mM) in the presence of 118 mM K. Hyperpolarized glands released 1280 +/- 135 ng per pulse and depolarized glands 831 +/- 98 ng per pulse (n = 29). 2. While the dihydropyridine Ca channel blocker nitrendipine inhibited secretion in hyperpolarized glands with an IC50 of 214 nM, in depolarizing conditions the drug was much more potent (IC50 = 0.99 nM). In contrast, the inorganic Ca channel blocker cadmium inhibited secretion with the same potency both in hyperpolarized or depolarized glands. 3. Cinnarizine, diltiazem and verapamil exhibited intermediate degrees of voltage-dependence in blocking secretion. The IC50 ratios between hyperpolarized and depolarized glands were 215, 36, 19, 8 and 0.76 respectively for nitrendipine, cinnarizine, diltiazem, verapamil and cadmium. Because the experimental design (strong depolarization in the absence of Ca) favours the highest opening probability of Ca channels, it seems that these drugs bind preferentially to their receptors when these channels are in their open state. 4. Variable voltage-dependent effects of the five Ca channel blockers on adrenomedullary catecholamine release suggests different sites and mechanisms of action on, or near L-type Ca channels in chromaffin cells. In addition, these findings might help to explain why these drugs exhibit tissue selectivity and why they act differently in normal polarized as compared to ischaemic depolarized cells.


Diet supplementation with commercial enzymatically-hydrolyzed egg white peptides ameliorates the severity of allergy in a mouse model of egg white allergy.
Commercial spray-dried egg white (S-EW) is often used for oral immunotherapy (OIT). Peptifine® (PF), a commercial preparation of enzymatically-hydrolyzed egg white (EW) peptides, is considered safe OIT food. Here, we examined the therapeutic effect of PF or S-EW in a mouse model of EW allergy. Sensitized female BALB/c mice underwent 4-week OIT by supplementation of 19% casein diet with 1% PF (PF group) or S-EW (S-EW group), and non-supplementation of 20% casein diet (non-OIT group). Non-sensitized mice acted as the non-allergy group. Oral and intraperitoneal EW challenges were performed and allergic biomarkers were determined. Changes in rectal temperature after oral challenge were comparable in the allergy groups. However, after intraperitoneal challenge, rectal temperature decrease in the PF and S-EW groups was lower than in the non-OIT group. After 4 weeks, plasma levels of ovalbumin- and ovomucoid-specific antibodies were assessed; IgE levels in the PF and S-EW groups were lower than those in the non-OIT group. Interleukin-4 secretion after EW challenge was significantly lower in splenocyte cultures derived from PF and S-EW groups than in the non-OIT group. Furthermore, the percentage of CD4+ Foxp3+ splenocytes in the PF group was significantly higher than that in the non-OIT and S-EW groups. Oral gavage of 40 mg PF did not induce an allergic response in sensitized mice with EW. Diet supplementation with 1% PF mildly ameliorated the severity of allergy in mouse with EW allergy, indicating that PF is a safe OIT food.


Polycyclic aromatic hydrocarbons (PAHs) in agricultural soil and vegetables from Tianjin.
Several types of vegetables were collected from two contaminated sites in Tianjin, China. The bulk soil and the rhizosphere soil samples were also collected from the same plots. Sixteen PAHs in the samples were measured. The total concentrations of PAH16 in the bulk soil from the two sites were 1.08 and 6.25 microg/g, respectively, with similar pattern. The concentrations of PAH16 and individual compounds in the rhizosphere were significantly higher than those in the bulk soil with mean values of 2.25 and 7.82 microg/g for the two sites, respectively. The contents of both total and dissolved organic matter in the rhizosphere were also higher than those in the bulk soil. Almost all PAH compounds studied were detected in both roots and aerial parts of the vegetables studied. Abundance of higher molecular weight PAHs in vegetable, however, was lower than that in soil. Concentrations of PAH16 in vegetable were higher than those reported in the literature for other areas. It appears that agricultural soils and vegetables in Tianjin, especially those from the site located immediately next to an urban district and irrigated with wastewater for several decades, are severely contaminated by PAHs. Among the eight types of vegetable studied, the highest concentration of PAHs was found in cauliflower. By average, the concentration of PAH16 in the aerial part of vegetables was 6.5 times higher as that in vegetable root, suggesting that foliar uptake is the primary transfer pathway of PAHs from environment to vegetables.


Incidence, Risk Factors and Outcomes of Sepsis in Critically Ill Post-craniotomy Patients: A Single-Center Prospective Cohort Study.
Data concerning the epidemiology of sepsis in critically ill post-craniotomy patients are scarce. This study aimed to assess the incidence, risk factors, and outcomes of sepsis in this population. This was a single-center prospective cohort study. Post-craniotomy patients admitted to the intensive care unit (ICU) were screened daily for the presence of infection and sepsis. Of the 900 included patients, 300 developed sepsis. The cumulative incidence of sepsis was 33.3% [95% confidence interval (CI), 30.2-36.4%]. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower Glasgow Coma Scale (GCS) on the first postoperative day were independent risk factors of sepsis. Septic patients had higher hospital mortality (13.7 vs. 8.3%, P = 0.012), longer ICU length of stay (LOS) (14 vs. 4 days, P < 0.001), longer hospital LOS (31 vs. 19 days, P < 0.001), and higher total medical cost (CNY 138,394 vs. 75,918, P < 0.001) than patients without sepsis. Sepsis is a frequent complication in critically ill post-craniotomy patients. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower GCS on the first postoperative day were independent risk factors of sepsis.


Post-dispersal seed removal by ground-feeding rodents in tropical peatlands, Central Kalimantan, Indonesia.
Forested tropical peatlands in Southeast Asia are being rapidly converted to agriculture or degraded into non-forest vegetation. Although large areas have been abandoned, there is little evidence for subsequent forest recovery. As part of a study of forest degradation and recovery, we used seed removal experiments and rodent surveys to investigate the potential role of post-dispersal seed predation in limiting the regeneration of woody plants. Two 14-day seed removal trials were done in deforested and forested peatland habitat in Central Kalimantan, Indonesia. Seeds of Nephelium lappaceum, Syzygium muelleri, Artocarpus heterophyllus (all animal-dispersed) and Combretocarpus rotundatus (wind-dispersed) were tested. Significantly more seeds (82.8%) were removed in forest than non-forest (38.1%) and Combretocarpus had the lowest removal in both habitats. Most handled seeds were eaten in situ and little caching was observed. Six species of rodents were captured in forest and five in non-forest. The most trapped taxa were three Maxomys spp. in forest (85.5% of individuals) and Rattus tiomanicus in non-forest (74.8%). Camera traps confirmed that rodents were responsible for seed removal. Seed predation in deforested areas, which have a much lower seed rain than forest, may contribute to the low density and diversity of regenerating forest.


An Electrophysiological Study of Aging and Perceptual Letter-Matching.
Background: Previous studies on perceptual letter-matching have found that younger and older adults showed "fast-same" effects for response time and "false-different" effects for errors but the effects were more pronounced for older adults. According to the Noisy Operator Theory, internal noise in visual processing distorts "same" trials into appearing different whereas distortion for "different" trials does not affect performance. Older adults have a "noisier" representation of items within perceptual processing which can impact perceptual matching. However, EEG measures may provide a more direct measure of letter-matching decisions. Methods: We measured the P300 event-related potential (ERP) amplitude, an index of familiarity in stimulus categorization, and behavioral measures (response time and accuracy) to assess letter-matching performance. Results: Individuals responded faster to "same" trials than to "different" trials but were less accurate. Older adults showed similar P300 amplitudes across trial type whereas younger adults produced a larger amplitude for "same" than "different" trials, suggesting that older adults showed less familiarity for "same" trials than did younger adults - a prediction of the Noisy Operator Theory. Conclusions: These ERP results are consistent with the Noisy Operator Theory - suggesting that an age-related increase in internal noise affected letter-matching performance.


Efficient peroxymonosulfate activation by biochar-based nanohybrids for the degradation of pharmaceutical and personal care products in aquatic environments.
Recently, pharmaceutical and personal care products (PPCPs) have been of wide concern due to their ecological toxicity, persistence, and ubiquity in aquatic environments. Peroxymonosulfate-based advanced oxidation processes (PMS-AOPs) have shown great potential for eliminating PPCPs due to their superior oxidation ability and adaptability. Biochar-based nanohybrids have been employed as emerging catalysts for peroxymonosulfate (PMS) activation. Until now, few researchers have summarized PMS activation by biochar-based catalysts for PPCPs removal. In this review, the types, sources, fates, and ecological toxicities of PPCPs were first summarized. Furthermore, various preparation and modification methods of biochar-based catalysts were systematically introduced. Importantly, the application of activating PMS with biochar-based multifunctional nanocomposites for eliminating PPCPs was reviewed. The influencing factors, such as catalysts dosage, PMS dosage, solution pH, temperature, anions, natural organic matters (NOMs), and pollutants concentration were broadly discussed. Biochar-based catalysts can act as electron donors, electron acceptors, and electron shuttles to activate PMS for the removal of PPCPs through radical pathways or/and non-radical pathways. The degradation mechanisms of PPCPs are correlated with persistent free radicals (PFRs), metal species, defective sites, graphitized degree, functional groups, electronic attributes, and the hybridization modes of biochar-based catalysts. Finally, the current problems and further research directions on the industrial application of biochar-based nanocomposites were proposed. This study provides some enlightenment for the efficient removal of PPCPs with biochar-based catalysts in PMS-AOPs.


Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations.
The aim of the present study was to ascertain the percentage of left apical myocardial apoptosis in three-vessel coronary artery bypass grafting patients quantitatively and the impact of ischemic preconditioning. Twenty-one patients with three-vessel disease who had elective coronary artery bypass grafting were randomized in a ratio of 2:1 to ischemic preconditioning (n = 14) or a control group (n = 7). The ischemic preconditioning protocol was established by two cycles of ascending aorta occlusion for 2 minutes followed by 3 minutes of reperfusion. Myocardial samples from the apex of the left ventricle were taken using a Tru-Cut needle before aortic cross-clamping and immediately after declamping. The percentage of apoptosis was analyzed by TUNEL methods. Data on hemodynamics and biochemical markers were collected. Low levels of myocardial apoptosis were found before the operation (0.01% +/- 0.00%). During the early reperfusion period, the percentage of myocardial apoptotic cells significantly increased (0.15% +/- 0.05%, p = 0.008). Ischemic preconditioning significantly improved cardiac index and right ventricular ejection fraction recovery after the operation (p = 0.036 and 0.001 respectively, repeated measure) but had no effect on myocardial apoptosis before and after the operation (0.01 +/- 0.00 versus 0.01 +/- 0.00, p = 0.658 and 0.12% +/- 0.04% versus 0.23% +/- 0.14%, p = 0.302). Cardioplegic myocardial ischemia during open heart operation was associated with induction of cardiomyocyte apoptosis in humans. Attenuation of postoperative cardiac dysfunction by ischemic preconditioning appeared to be independent of apoptosis.


The amyloplast proteome of potato tuber.
Potato (Solanum tuberosum) is the fourth largest crop worldwide in yield, and cv. Kuras is the major starch potato of northern Europe. Storage starch is packed densely in tuber amyloplasts, which become starch granules. Amyloplasts of soil-grown mini-tubers and agar-grown micro-tubers of cv. Kuras were purified. The mini-tuber amyloplast preparation was enriched 10-20-fold and the micro-tuber amyloplast approximately fivefold over comparative total protein extracts. Proteins separated by SDS-PAGE were digested with trypsin, analysed by mass spectrometry and identified by mascot software searches against an in-house potato protein database and the NCBI non-redundant plant database. The differential growth conditions for mini- and micro-tubers gave rise to rather different protein profiles, but the major starch granule-bound proteins were identical for both and dominated by granule-bound starch synthase I, starch synthase II and alpha-glucan water dikinase. Soluble proteins were dominated by starch phosphorylase L-1, other large proteins of the classes 'starch and sucrose metabolism', 'pentose phosphate pathway', 'glycolysis', 'amino acid metabolism', and other proteins such as plastid chaperonins. The majority of the identified proteins had a predicted plastid transit peptide, supporting their presence in the amyloplast. However, several highly expressed proteins had no transit peptide, such as starch phosphorylase H, or had a predicted mitochondrial location. Intriguingly, all polyphenol oxidases, a family of enolases, one transketolase, sulfite reductase, deoxynucleoside kinase-like and dihydroxy-acid dehydrase had twin-arginine translocation motifs, and a homologue to dihydrolipoamide dehydrogenase had a Sec (secretory) motif; these motifs usually target thylakoid-like structures.


Prehabilitation for medically frail patients undergoing surgery for epithelial ovarian cancer: a cost-effectiveness analysis.
To assess the potential cost-effectiveness of prehabilitation in medically frail patients undergoing surgery for epithelial ovarian cancer (EOC). We created a cost-effectiveness model evaluating the impact of prehabilitation on a cohort of medically frail women undergoing primary surgical intervention for EOC. Cost was assessed from the healthcare system perspective via (1) inpatient charges from 2018-2019 institutional Diagnostic Related Grouping data for surgeries with and without major complications; (2) nursing facility costs from published market surveys. Major complication and non-home discharge rates were estimated from the literature. Based on published pilot studies, prehabilitation was determined to decrease these rates. Incremental cost-effectiveness ratio for cost per life year saved utilized a willingness-to-pay threshold of $100,000/life year. Modeling was performed with TreeAge software. In a cohort of 4,415 women, prehabilitation would cost $371.1 Million (M) versus $404.9 M for usual care, a cost saving of $33.8 M/year. Cost of care per patient with prehabilitation was $84,053; usual care was $91,713. When analyzed for cost-effectiveness, usual care was dominated by prehabilitation, indicating prehabilitation was associated with both increased effectiveness and decreased cost compared with usual care. Sensitivity analysis showed prehabilitation was more cost effective up to a cost of intervention of $9,418/patient. Prehabilitation appears to be a cost-saving method to decrease healthcare system costs via two improved outcomes: lower complication rates and decreased care facility requirements. It represents a novel strategy to optimize healthcare efficiency. Prospective studies should be performed to better characterize these interventions in medically frail patients with EOC.


Severe intravascular hemolysis after aortic valve replacement: reversal by left ventricular apico-abdominal aortic composite conduit.
Severe intravascular hemolysis developed following aortic valve replacement with a No. 17 Björk-Shiley prosthesis in a patient with a diminutive aortic annulus. At reoperation, a residual gradient of 54 mm. Hg and no evidence of perivalvular leak were found. A second left ventricular outflow tract between the apex and the supraceliac abdominal aorta was fashioned with a special rigid (Pyrolite) prosthesis and a heterograft valved composite conduit. The gradient was reduced to 5 mm. Hg and hemolysis was reversed. We have now created double-outlet left ventricles for primary or recurrent left ventricular outflow tract obstructions of various etiologies in 13 other pediatric and adult patients. The longest follow-up is approaching 18 months. All gradients have been sharply reduced and all patients are asymptomatic.


Current and future costs of obesity in Sweden.
Obesity is a growing health issue. This study estimated the costs of obesity among people aged 25-84 years in Sweden using disease and non-disease specific attributable fractions from published data. A prognosis of costs of obesity in 2030 is presented. Diseases related to obesity and their respective risks and population attributable fraction were retrieved by literature review. Longitudinal data on age and sex related prevalence of obesity was used to construct three scenarios for costs of obesity in 2030. Nearly 4% of all deaths among people 25-84 years in 2016 (n = 3,400) were attributed to obesity. Obesity cost EUR 2.7 billion in 2016, or EUR 377 per inhabitant aged ≥25 years. Non-health care costs were dominant and represented 80% of total societal costs. Main drivers were premature mortality (28%) and permanent sick leave (37%). If the proportion of obese remain at 2016 level, costs will increase 9% by 2030, but with continued linear growth, costs will increase by 66%. The responsibility, costs and treatment fall on several actors with a considerable burden falling on the individual and the society at large. New health promoting interventions and policy programs are needed and must be evaluated in terms of resource use and expected return.


The Mysterious Role of Epidural Fat Tissue in Spine Surgery: A Comprehensive Descriptive Literature Review.
Though both neurosurgeons and orthopedic spinal surgeons are keenly aware of the clinical importance of epidural fat (EF), surgical practice varies amongst individual surgeons and across both fields. Thus, an in-depth understanding of the anatomical structure and composition of EF is vital, as it will play a significant role in the therapeutic management and the surgical choice of treatment. We aim to extensively review the anatomical and biological properties of EF and further outline the surgical importance of EF management. (i) MEDLINE search 1966-July 2019. Keywords: Review of the Literature. Authorship, Meta-analysis, Descriptive/Narrative overview; (ii) CINAHL search from 1982 to May 2019. Keywords: Review of the Literature spinal epidural fat; Authorship; Meta-analysis; Descriptive/Narrative overview; (iii) Hand searches of the references of retrieved literature; (iv) Personal and college libraries were searched for texts on research methods and literature reviews; and (v) 200 articles were downloaded, 50 were excluded because of similarity of topics and also because of new update on the same topics. (vi) Discussions with experts in the field of reviews of the literature. Though excessive or reductive amounts of EF usually exacerbates neurological symptoms and lead to various pathologic conditions such as spinal epidural lipomatosis, but there is no basic science, experimental, or clinical research that proves the role of EF in the aforementioned pathologic situations. Anatomical illustration, biological function and properties of EF knowledge may lead to changes in the stages of the surgical approach to avoid postoperative complications. However, the role of EF is exclusively bound to a scientific hypothesis as one cannot be sure if an excessive or reductive amount in EF is entirely responsible for the pathologic findings, or just only an incidental finding.


Minimization of the threshold voltage parameter of the co-doped ZnO doped liquid crystals by machine learning algorithms.
This study aims to examine the influence of the co-doped semiconductor nanostructure (Al-Cu):ZnO on the electro-optical properties of the E7 coded pure nematic liquid crystal structures and minimize the threshold voltage of pure E7 liquid crystal. To determine the ideal concentration ratios of the materials for the minimum threshold voltage, we employed different machine learning algorithms. In this context, we first produced twelve composite structures through lab experimentation with different concentrations and created an experimental dataset for the machine learning algorithms. Next, the ideal concentration ratios were estimated using the AdaBoost algorithm, which has an [Formula: see text] of 96% on the experimental dataset. Finally, additional composite structures having the estimated concentration ratios were produced. The results show that, with the help of the employed machine learning algorithms, the threshold voltage of pure E7 liquid crystal was reduced by 19% via the (Al-Cu):ZnO doping.


A check on the memory deficit hypothesis of obsessive-compulsive checking.
A number of recent studies have challenged the hypothesis that patients with obsessive-compulsive disorder (OCD) display global memory deficits. An alleviated form of the memory deficit hypothesis posits that OCD patients share deficits to vividly recall memory episodes. According to the latter view, checking rituals can be understood as counter-productive coping strategies to "enrich" memory episodes in order to make them more distinctive. A source memory task was administered to 27 OCD (17 checkers) and 51 healthy participants. Along with confidence judgments, a remember-know procedure was employed to assess whether OCD patients display problems with conscious/vivid recollection. Patients with or without checking compulsions did not exhibit differences to controls on source memory accuracy and meta-memory. Patients forgot more self-generated items, which, however, was related to comorbid depressive but not OCD symptoms. Findings challenge the ubiquity of memory deficits in OCD. To account for the inconclusive pattern of results in the literature, it is suggested that patients mistrust their memories and adopt checking rituals only when perceived responsibility is inflated.


Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy.
T cells expressing chimeric antigen receptors (CARs) have achieved major clinical success in patients with hematologic malignancies. However, these treatments remain largely ineffective for solid cancers and require significant time and resources to be manufactured in an autologous setting. Developing alternative immune effector cells as cancer immunotherapy agents that can be employed in allogeneic settings is crucial for the advancement of cell therapy. Unlike T cells, Vα24-invariant natural killer T cells (NKTs) are not alloreactive and can therefore be generated from allogeneic donors for rapid infusion into numerous patients without the risk of graft-versus-host disease. Additionally, NKT cells demonstrate inherent advantages over T-cell products, including the ability to traffic to tumor tissues, target tumor-associated macrophages, transactivate NK cells, and cross-prime tumor-specific CD8 T cells. Both unmodified NKTs, which specifically recognize CD1d-bound glycolipid antigens expressed by certain types of tumors, and CAR-redirected NKTs are being developed as the next generation of allogeneic cell therapy products. In this review, we describe studies on the biology of NKTs and other types of innate-like T cells and summarize the clinical experiences of unmodified and CAR-redirected NKTs, including recent interim reports on allogeneic NKTs.


Relationships between socio-economic status and lottery gambling across lottery types: neighborhood-level evidence from a large city.
Lottery gambling participation tends to be higher among lower socio-economic status (SES) individuals, but it is unclear how this relationship differs as a function of lottery type. We estimated how the relationship between SES and lottery gambling rates varies across different types of lottery gambling: fixed-prize, progressive-prize (jackpot) and instant-win (scratch card) lottery tickets in a large Canadian city. Neighborhood-level lottery purchase data obtained from the Ontario Lottery and Gaming Commission were analysed in conjunction with demographic data. Mixed-effects regression was used to assess simultaneously how neighborhood-level SES predicts per-person lottery gambling rates across fixed-prize, progressive-prize lottery and instant-win lotteries. Neighborhoods in Toronto, Ontario, Canada in the years 2012-15. Per-capita sales in dollars (CAD) of fixed-prize lottery, progressive-prize lottery and instant-win tickets in Toronto postal codes. SES was estimated as a composite of income, years of education and white-collar employment. Lower-SES neighborhoods engaged in higher rates of lottery gambling overall [β = -0.084, standard error (SE) = 0.24, P = 0.0007]. The predictive effect of SES varied significantly by lottery type (fixed-prize: β = -0.105, SE = 0.004, P < 0.0001, instant-win: β = -0.054, SE = 0.004, P < 0.0001; relative to progressive-prize). The predictive effect of SES was strongest for fixed-prize lotteries and weakest for progressive-prize lotteries, such that we did not observe a significant predictive effect of SES for progressive-prize lotteries (β = -0.031, SE = 0.024, P = 0.198). People in lower socio-economic status neighborhoods in Toronto, Canada appear to engage in more lottery gambling than those in higher socio-economic status neighborhoods, with the difference being largest for fixed prize lotteries followed by instant win lotteries, and no clear difference for progressive prize lotteries.


Concepts, Terms, and Mental Models: Everyday Challenges to Older Adult Social Media Adoption.
Social connection and social support are strong predictors of wellbeing, but maintaining social relations often becomes more difficult at older ages. Because social media enhance feelings of connectedness and reduce feelings of loneliness, they may present accessible and relatively low cost mechanisms to enhance life quality at older ages. Using data gathered from two focus groups of potential older adult social media learners, we explored the physical and cognitive challenges to social media use, perceptions of social media benefits, and conceptual barriers to use. Findings support earlier studies that identify perceived benefit as important to social media adoption at older ages, and extend these by identifying that a lack in conceptual knowledge of these technologies is an additional barrier to use. We then discuss the cognitive implications of gaining this knowledge.


The therapeutic effect and mechanism of Rapamycin combined with HO-3867 on monocrotaline-induced pulmonary hypertension in rats.
This study test was designed to investigate the possible modulatory effect of rapamycin combined with HO-3867 in monocrotaline(MCT)-induced pulmonary arterial hypertension in rats. We hypothesized that combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced rat pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). 2 weeks later, rapamycin (2 mg/kg i.p.) and HO3867 (10 mg/kg i.h.) were administered daily, alone and in combination, for 2 weeks. Right ventricular systolic pressure, echocardiography were recorded and then rats were sacrificed. Histological analysis of pulmonary arteries medial wall thickness, right ventricular hypertrophy index (RVHI), the ratio of right ventricular to body weight, and collagen volume fraction (CVF) of right ventricular were performed. Moreover, the expression of t-STAT3, p-STAT3, t-Akt, p-Akt in lung and t-STAT3, p-STAT3, t-S6, p-S6 in right ventricular were examined. The result showed that combined treatment provided a considerable improvement toward maintaining hemodynamic changes, lung vascular remodeling as well as amending RV remodeling and function. Furthermore, Combined treatment can normalize the protein levels of two signal pathways in lung and heart tissue, where p-S6 or p-Akt significantly decreased compared to HO-3867 alone, or p-STAT3 significantly reduced compared to rapamycin alone. In conclusion, combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced PAH in rats.


Hexavalent chromium disrupts the skin barrier by targeting ROS-mediated mitochondrial pathway apoptosis in keratinocytes.
Hexavalent chromium (Cr(VI)), a toxic heavy metal, is ubiquitous in daily life. Exposure to this toxic substance in occupational settings can cause dermatitis and cancer. As the body's largest organ, the skin plays a crucial role in protecting the organism against external aggressions. While previous studies have focused on the effects of Cr(VI) on skin inflammation, this study investigates the potential toxicity of Cr(VI) from the skin barrier and integrity perspective. The in vivo results of this study showed that mice exposed to Cr(VI) experienced skin deterioration and hemorrhaging, as well as a reduction in the thickness of the collagen fiber layer. TUNEL and Occludin staining results revealed that Cr(VI)'s toxicity primarily targeted keratinocytes. Experiments in vitro demonstrated that Cr(VI) treatment decreased the activity of HaCaT cells, altered cell morphology, and increased LDH secretion. Further research revealed that Cr(VI) could modify membrane permeability, impair membrane integrity, and reduce the protein expression of ZO-1 and Occludin. In addition, it was discovered that Cr(VI) promoted cell apoptosis and inhibited AKT activation. However, the addition of a caspase inhibitor and an AKT activator prevented Cr(VI)-induced injury to the cell membrane barrier, indicating that apoptosis plays a crucial role in this process. The addition of three apoptotic pathway inhibitors, confirmed that Cr(VI) damaged the cell barrier through ROS-mediated mitochondrial pathway apoptosis. Moreover, the use of a ROS inhibitor significantly reduced Cr(VI)-induced apoptosis and cell barrier injury. In conclusion, this study provides an experimental foundation for the treatment of skin injury caused by Cr(VI).


Two-dimensional boron nanosheets for selective enrichment and detection of cis-diol compounds by surface-assisted laser desorption/ionization time-of-flight mass spectrometry.
Surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS) is an effective method for detecting of low-mass molecules. In this study, two-dimensional boron nanosheets (2DBs) were fabricated through thermal oxidation etching and coupling liquid exfoliation technologies, and applied as a matrix and selective sorbent for detecting cis-diol compounds by SALDI-TOF MS. The outstanding nanostructure and boric acid active sites of 2DBs endow them with sensitivity for cis-diol compound detection, excellent selectivity, and low background interference for complex samples. The specific in-situ enrichment faculty of the 2DBs as a matrix was investigated by SALDI-TOF MS using glucose, arabinose, and lactose as model analytes. In the presence of 100 -fold more interfering substances, the 2DBs showed high selectivity against cis-diol compounds, and exhibited a better sensitivity and a reduced limit of detection through enrichment treatment than graphene oxide matrices. The linearity, limit of detection (LOD), reproducibility, and accuracy of the method were evaluated under optimized conditions. The results showed that the linear relationships of six saccharides remained in the range of 0.05-0.6 mM with a correlation coefficient r ≥0.98. The LODs of six saccharides were 1 nM (glucose, lactose, mannose, fructose) and 10 nM (galactose, arabinose). Sample-to-sample (n = 6) with relative standard deviations (RSDs) of 3.2% to 8.1% were observed. Recoveries (n = 5) of 87.9-104.6% were obtained at three spiked levels in the milk samples. The proposed strategy promoted the development of a matrix for use with SALDI-TOF MS detection, in which the UV absorption properties and enrichment capabilities of 2DBs were combined.


Practical fixed-time observer-based generalized cascade predictor design for synchronization of integrator systems with delays and complex unknowns.
This paper studies output feedback leaderless synchronization problem for high-order integrator chains subject to nonlinear dynamics, measurement noises, matched disturbances, and time delays in both input and output. First, we consider the varying normal-scale input delay case and propose a novel extended state observer (ESO)-based predictor device for each agent using relative output of neighbors. Then, in combination with integral sliding mode, leaderless fully distributed synchronization protocols are designed which can highly compensate for delays and unknowns. In particular, the ESO combines the transient performance of fixed-time algorithms with the continuous/smooth, anti-noise and low-cost strengths of linear algorithm via linear structure and time base gains. Also, any disturbances considered in this protocol are not generated by known exosystem and hence the proposed anti-disturbance time delay compensation scheme is more general. Second, aiming to cope with a larger class of input delays, the above device is extended to a ESO-based cascade predictor device. Synchronization analysis is placed in the Lyapunov-Krasovskii functional frame and sufficient conditions are deduced to ensure that the synchronization errors converge to a residual set in fixed time. Detailed numerical simulation studies and thorough comparisons are provided to verify the effectiveness and superiority of the designed ESO and devices.


[Relation between body fat distribution, insulin levels and glucose tolerance in obese females].
Relationship between body fat distribution, serum insulin, and glucose tolerance in obese, non-diabetic women. Recent studies suggest that hyperinsulinemia and upper body obesity are predictive factors for the development of non-insulin-dependent diabetes mellitus. To further characterize the relationship between body fat distribution, serum insulin, and glucose tolerance an oral glucose tolerance test was performed in 48 obese, non-diabetic women. Fasting insulin levels were correlated to both total body fat calculated as body mass index (r = 0.58, p less than 0.001) and upper body fat distribution expressed as waist-to-hip ratio (WHR, r = 0.47, p less than 0.01). In the women with upper body fat localization (WHR greater than 0.90) significantly higher basal and glucose-stimulated insulin concentrations were established than in the women with a lower body type of obesity (WHR less than 0.78) (basal insulin 27.4 +/- 11.5 vs. 15.4 +/- 8.8 mU/l, p less than 0.05, insulin area 779 +/- 320 vs. 468 +/- 237 U, p less than 0.05). They also had impaired glucose tolerance (glucose area 925 +/- 139 vs. 633 +/- 147 U, p less than 0.01). Fasting triglyceride concentrations were correlated both with WHR (r = 0.63, p less than 0.001) and fasting insulin (r = 0.33, p less than 0.05) but not with BMI (r = -0.02, n.s.). A positive association was found between systolic and diastolic blood pressure and both WHR (r = 0.43 and r = 0.44 resp., p less than 0.01) and BMI (each r = 0.35, p less than 0.05). Interestingly, basal insulin was also associated with blood pressure (r = 0.30, p less than 0.1, and r = 0.40, p less than 0.01 resp.).(ABSTRACT TRUNCATED AT 250 WORDS)


On the imitation of CP gait patterns by healthy subjects.
The comparison of gait imitated by healthy subjects with real pathological CP gaits is expected to contribute to a better distinction between primary deviations directly induced by neurological troubles and secondary compensatory deviations in relation with the biomechanics of the pathological gait. However, the ability of healthy subjects for imitating typical CP gaits such as "jump" or "crouch" gaits still remains to be determined. The present study proposes to investigate healthy subjects imitating these typical CP gait patterns. 10 healthy adult subjects performed three types of gait: one "normal" and two imitated "jump" and "crouch" gaits. Kinematics and kinetics of the hip, knee and ankle were computed in the sagittal plane. Rectified normalized EMG was also analysed. Our data were compared with reference data. For the statistical analysis, the coefficient of multicorrelation has been used. It has been demonstrated that healthy subjects were able to voluntarily modify their gait pattern with a high level of intra-session and inter-subject reproducibility as quantified by a CMC values higher than 0.76 for all parameters. The comparison with literature reference data showed that healthy subjects not could perfectly reproduce a CP gait, however could only simulate the main characteristics of "crouch" and "jump" gaits pattern. As a perspective, pathological gaits imitated by healthy subjects could be used as valuable additional material to analyse the relationship between a voluntarily modified posture and the altered muscle activation to explore a new paradigm on pathological gait pattern analysis and musculoskeletal modelling.


Ankle Evaluation in Active Rheumatoid Arthritis by Ultrasound: A Cross-Sectional Study.
Ankle joint evaluation is underestimated in many clinical and sonographic scores used for evaluation and follow-up of rheumatoid arthritis (RA) patients. Agreement on examination parameters is poor among sonographic scores that include the ankle joint. More effort is needed to detect the value of ankle joint examination in RA and assessment of ultrasonographic signs according to frequency, disease duration and activity. The objective of this study was to use ultrasound (US) to detect ankle involvement in active RA and to compare findings with disease duration, disease activity and assessment of ankle bone erosion. A total of 63 RA patients with active disease and 20 controls were included in the study. The tibiotalar and talonavicular joints were examined by US for synovitis and/or effusion in gray-scale and power Doppler modes. The anterior, lateral and posterior ankle tendons were examined for tenosynovitis and tendinosis. Mean age was 35.1 ± 8.3 y, mean disease duration was 22.7 ± 9.6 mo and the mean 28-joint Disease Activity Score-erythrocyte sedimentation rate was 3.05 ± 0.66. Ankle involvement was seen in 28 patients (44.4%). The most frequent pathologies detected were tenosynovitis (30.2%), followed by synovitis (18.3%), erosion (8.7%) and tendinosis (4%). The earliest sonographic signs were tenosynovitis, followed by synovitis, erosion and tendinosis. The right ankle exhibited greater involvement than the left ankle, which was significant with respect to erosions (p = 0.009). The most common tendon affected by tenosynovitis was the tibialis anterior (22.2%), followed by the tibialis posterior (20.6%). Tenosynovitis, especially of the tibialis anterior and posterior, tibiotalar synovitis and erosions should be considered in future US ankle scores for the assessment of RA.


Detection, prevalence and analysis of emerging porcine parvovirus infections.
A number of newly identified porcine parvoviruses had been described during the last decade, but the presence and prevalence of these viruses are unknown in Hungary and only partly known for Europe. The present study was conducted to detect and measure the prevalence of these viruses, namely porcine parvovirus (PPV) 2, PPV3, PPV4, porcine bocavirus (PBoV) 1, PBoV2, PBo-likeV and the 6V and 7V parvoviruses. The prevalence of PPV1 and porcine circovirus type 2 (PCV2) was also investigated. Faecal samples, blood serum samples, organ tissues, foetuses and semen were collected from different swine herds in Hungary and tested by polymerase chain reaction methods specific for the different viruses. The results indicated that all of the examined parvoviruses were present in Hungary, hence in Europe. The prevalence was 18.1% for PCV2, 0.5 % for PPV1, 6.4% for PPV2, 9.7% for PPV3, 6.4% for PPV4, 1.5% for PBo-likeV, 4.8% for PBoV1 and PBoV2 and 1.8% for 6V and 7V. Based on the analysis of partial PPV4 and PBo-likeV sequences, these viruses showed a high degree of sequence conservation, whereas PPV3 and the majority of PPV2, PBoV1, PBoV2, 6V and 7V sequences showed higher variability. Possible sites of recombination were also identified between PBoV1 and PBoV2 genomes.


Bradykinin receptors in mouse and rat isolated superior cervical ganglia.
1. The ability of bradykinin and its analogues to depolarize rat and mouse superior cervical ganglia was studied by use of in vitro grease-gap recording techniques, and the ability of antagonists selective for bradykinin receptor subtypes to block their effects was examined. 2. Bradykinin (3 microM) depolarized ganglia from both species, although the magnitude of the maximal response was less in mouse (15 +/- 5%, n = 7) than rat tissue (33 +/- 6%, n = 7), relative to muscarine (1 microM). 3. Interleukin 1 beta (30 u ml-1 for 18 h at 37 degrees C) increased the depolarization caused by bradykinin (3 microM) in mouse ganglia from 15% to 54% (P < 0.001, n = 12). Responses to the B1 receptor agonist, [des-Arg10]-kallidin (3 microM) were similarly potentiated but this was only detected after inhibition of peptidase activity with 10 microM captopril (4% to 35%, n = 5). 4. In ganglia from both species the rank order of agonist potency was bradykinin = [Lys0]-bradykinin >> [des-Arg10]-kallidin. However, like responses to [des-Arg10]-kallidin in mouse tissue, both the potency of bradykinin and the maximal depolarization achieved (EC50 = 912 nM; 80%, n = 11) was enhanced following inhibition of angiotensin converting enzyme with 10 microM captopril (EC50 = 50 nM; 135%, n = 4). 5. Responses to bradykinin were selectively antagonized by the B2 receptor antagonist, Hoe 140 but not by the B1 antagonist, [Leu8]-bradykinin1-8. From Schild analysis the pA2 value for Hoe 140 in mouse tissue was 9.65, although the slope of the regression line was significantly greater than unity, indicating non-competitive kinetics (slope = 1.88 +/- 0.18, n = 9). The depolarization caused by [Lys0]-bradykinin was also antagonized by Hoe 140 (3 nM).6. Thus the predominant bradykinin receptor in mouse superior cervical ganglia is compatible with a B2 subtype. Furthermore the depolarizations caused by B1 and B2 agonists in this tissue can be increased following exposure to interleukin l beta, and by blocking peptide degradation with captopril.


Psychoemotional factors and their influence on the quality of life in patients with GERD.
Patient-reported outcomes (PROs) are integral to determining the success of foregut surgical interventions and psychoemotional factors have been hypothesized to impact the quality of life of patients. This study evaluates the correlation between PROs-specifically the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) and the Laryngopharangeal Reflux Symptom Index (LPR-RSI)-and the recently validated Esophageal Hypervigilance Anxiety Scale (EHAS). We hypothesize that patients with higher EHAS scores have significantly elevated GERD-HRQL LPR-RSI compared to those with normal scores. EHAS has been developed and validated in chronic esophageal disorders, but clinical impact is unknown. In this retrospective study, 197 patients (38% men, average age 56 ± 16) completed the following surveys:(1) EHAS, (2) GERD-HRQL, and (3) LPR-RSI. All patients referred for surgical evaluation of GERD completed the surveys as part of their pre-operative workup and post-operative follow-up In bivariate analysis, EHAS correlated with both GERD-HRQL (r 0.53, P = <0.001) and LPR-RSI (r 0.36, P = 0.009). Accounting for potential confounding with sex and age in multivariable linear regression models, a higher GERD-HRQL score (β 0.38; 95% CI 0.29 to 0.48; P = <0.001; Semipartial R2 0.20) and a higher LPR-RSI score (β 0.21; 95% CI 0.13 to 0.29; P = <0.001; Semipartial R2 0.08) were independently associated with higher EHAS. The observed relationship between mental health and GERD symptom intensity is consistent with the biopsychosocial paradigm of illness. Future studies focused on post-surgical outcomes following the incorporation of EHAS into perioperative care is needed to evaluate its effectiveness as a clinical decision support tool in ARS.


Comprehensive analysis of mRNAs in the cerebral cortex in APP/PS1 double-transgenic mice with Alzheimer's disease based on high-throughput sequencing of N4-acetylcytidine.
N4-acetylcytidine (ac4C), a significant modified nucleoside, participates in the development of many diseases. Messenger RNAs (mRNAs) contain most of the information of the genome and are the molecules that transmit information from genes to proteins. Alzheimer's disease (AD) is a progressive neurodegenerative disease in which fibrillar amyloid plaques are present. However, it remains unknown how mRNA ac4C modification affects the development of AD. In the current study, ac4C-modified mRNAs were comprehensively analyzed in AD mice by ac4C-RIP-seq and RNA-seq. Next, a protein-protein interaction (PPI) network was constructed to examine the relationships between the genes with differential ac4C modification levels and their RNA expression levels. The differentially expressed genes (DEGs) acquired above were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further analyze the molecular mechanisms in AD. In total, 3312 significant ac4C peaks were found on 2512 mRNAs, 1241 of which were hyperacetylated and 1271 of which were hypoacetylated. In addition, 956 mRNAs with differential expression were found, including 520 upregulated mRNAs and 436 downregulated mRNAs. Overall, 134 mRNAs with simultaneous changes at the ac4C levels as well as RNA expression levels were identified via joint analysis. Then, through PPI network construction and functional enrichment analysis, 37 key mRNAs were screened, which were predominantly enriched in GABAergic synapses and the PI3K/AKT signaling pathway. The significant difference in the abundance of mRNA ac4C modification indicates that this modification is associated with AD progression, which may provide insight for more investigations of the potential mechanisms.


Imaging of Posttraumatic Arthritis, Avascular Necrosis, Septic Arthritis, Complex Regional Pain Syndrome, and Cancer Mimicking Arthritis.
This article focuses on the imaging of 5 discrete entities with a common end result of disability: posttraumatic arthritis, a common form of secondary osteoarthritis that results from a prior insult to the joint; avascular necrosis, a disease of impaired osseous blood flow, leading to cellular death and subsequent osseous collapse; septic arthritis, an infectious process leading to destructive changes within the joint; complex regional pain syndrome, a chronic limb-confined painful condition arising after injury; and cases of cancer mimicking arthritis, in which the initial findings seem to represent arthritis, despite a more insidious cause.


Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer hydrophobicity on PYY3-36 delivery.
The treatment for many diseases can be improved by developing more efficient peptide delivery technologies, for example, biodegradable polymers. In this work, photocrosslinked poly(ester anhydride)s based on functionalized poly(ε-caprolactone) oligomers were investigated for their abilities to achieve controlled peptide delivery. The effect of oligomer hydrophobicity on erosion and peptide release from poly(ester anhydride)s was evaluated by developing a sustained subcutaneous delivery system for an antiobesity drug candidate, peptide YY3-36 (PYY3-36). Oligomer hydrophobicity was modified with alkenylsuccinic anhydrides containing a 12-carbon alkenyl chain. PYY3-36 was mixed as a solid powder with methacrylated poly(ester anhydride) precursors, and this mixture was photocrosslinked at room temperature to form an implant for subcutaneous administration in rats. The oligomer hydrophobicity controlled the polymer erosion and PYY3-36 release as the increased hydrophobicity via the alkenyl chain prolonged polymer erosion in vitro and sustained in vivo release of PYY3-36. In addition, photocrosslinked poly(ester anhydride)s increased the bioavailability of PYY3-36 by up to 20-fold in comparison with subcutaneous administration of solution, evidence of remarkably improved delivery. In conclusion, this work demonstrates the suitability of photocrosslinked poly(ester anhydride)s for use in peptide delivery.


Microbial diversity of a mesophilic hydrogen-producing sludge.
A hydrogen-producing sludge degraded 99% of glucose at 36 degrees C and pH 5.5, producing a methane-free biogas (comprising 64% hydrogen) and an effluent comprising mostly butyrate, acetate, and ethanol. The yield was 0.26 l H2 g(-1) glucose and the production rate per gram of volatile suspended solids was 4.6 1 H2 day(-1). A 16S rDNA library was constructed from the sludge for microbial species determination. A total of 96 clones were selected for plasmids recovery, screened by denaturing gradient gel electrophoresis, and sequenced for rDNA. Based on the phylogenetic analysis of the rDNA sequences, 64.6% of all the clones were affiliated with three Clostridium species (Clostridiaceae), 18.8% with Enterobacteriaceae, and 3.1% with Streptococcus bovis (Streptococcaceae). The remaining 13.5% belonged to eight operational taxonomic units, the affiliations of which were not identified.


Determination of phenols and chlorophenols as trimethylsilyl derivatives using gas chromatography-mass spectrometry.
A rapid and simple method is described for the simultaneous determination of 6 phenols (phenol, o-, m-, p-cresol, catechol and resorcinol) and 19 chlorophenols (all mono-, di-, tri-, and tetrachlorophenol isomers and pentachlorophenol) present in aqueous samples. The method is based on derivatization with trimethylsilyl-N,N-dimethylcarbamate (TMSDMC). In contrast to other derivatization agents, TMSDMC instantaneously reacts with the phenolic compounds at room temperature and no further sample processing is necessary prior to instrumental analysis. The determination of the derivatives was performed by capillary gas chromatography-mass spectrometry (GC-MS). The stability of the most instable trimethylsilyl derivative (pentachlorophenol) was studied using different excess levels of the derivatization reagent. The derivatization method was tested on spiked water samples preconcentrated by solid phase extraction on Isolute ENV+ cartridge. The overall method gave detection limits of 0.01-0.25 microg/L for all compounds and < 0.05 microg/L for 17 of them.


Latent class analysis: an innovative approach for identification of clinical and laboratory markers of disease severity among COVID-19 patients admitted to the intensive care unit.
The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town. A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L; p < 0.001), end-organ dysfunction (creatinine, median value 79 µmol/L vs 69.5 µmol/L; p < 0.003), under-perfusion markers (lactate, median value 1.60 mmol/L vs 1.20 mmol/L; p < 0.001), abnormal cardiac function markers (median N-terminal pro-brain natriuretic peptide (NT-proBNP) 314 pg/ml vs 63.5 pg/ml; p < 0.001 and median high-sensitivity cardiac troponin (Hs-TropT) 39 ng/L vs 12 ng/L; p < 0.001), and acute inflammatory syndrome (median neutrophil-to-lymphocyte ratio 15.08 vs 8.68; p < 0.001 and median monocyte value 0.68 × 109/L vs 0.45 × 109/L; p < 0.001). The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU.


Effect of preoperative cimetidine and ranitidine on gastric secretion.
To decrease gastric volume and acidity prior to anesthesia and surgery and decrease the risk of aspiration, a prospective double-blind trial comparing two H2 receptor blockers, cimetidine and ranitidine, was performed. Analysis of gastric contents revealed both drugs to be extremely effective in raising gastric pH to the 6-7 range. However, ranitidine was shown to be more effective in decreasing gastric volume.


A rapid MALDI-TOF mass spectrometry-based method for categorization of Pseudomonas aeruginosa from blood cultures as susceptible or resistant to meropenem.
We developed and evaluated a simple, low-cost matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS)-based method for the detection of meropenem (MER) resistance in Pseudomonas aeruginosa directly from blood. A volume of 50 μL of positive-flagged blood culture (BC) was transferred in 450 μL brain heart infusion (BHI) broth to microtubes either containing MER (test) or not (control) at 25 or 50 mg/L. P. aeruginosa was categorized as resistant or susceptible on the basis of whether or not the isolates could be identified, respectively, in the presence of the antibiotic (3 h of incubation). When using BCs spiked with 99 P. aeruginosa isolates (64 MER-resistant and 35 MER-susceptible) the method correctly classified 88/99 isolates (88.9%). Correct categorization was achieved in 23/23 (100%) of P. aeruginosa isolates (17 MER-susceptible and 6 MER-resistant) from prospectively collected BCs. Our method may prove useful for early targeted or adjustment of empirical therapy in patients with P. aeruginosa bloodstream infections.


[Intensity of 14C-2-acetate incorporation into guinea pig brain and spinal cord phospholipids and cholesterol under normal conditions and following triorthocresylphosphate poisoning].
A severe form of chronic intoxication was caused in guinea pigs by a single intracutaneous inoculation of triorthocresyl phosphate (TOCP); the intensity of acetate-2(14)C incorporation into the brain stem and spinal cord phospholipids and cholesterol was investigated in vivo. In paralytic stage of the disease incorporation of 14C into phospholipids and cholesterol was found to be markedly depressed; the inhibition of the synthesis of these lipids was observed not only in the most vulnerable lumbo-sacral region of the spinal cord, but also in the brain stem. This finding is in favour of the systemic character of lipid metabolism disorder in the central nervous system and indicates alteration of oligodendrocyte metabolism caused by TOCP.


Comprehensive untargeted lipidomic analysis of sea buckthorn using UHPLC-HR-AM/MS/MS combined with principal component analysis.
Sea buckthorn is an important ecological and economic plant which has multiple bioactivities. The fruits and seeds of sea buckthorn are rich in oil. However, there are few studies on the differences of lipid profiles of sea buckthorn varieties. Herein, the lipidomic fingerprints of sea buckthorn was established. First, a mixture solvent of methanol and chloroform (2:1, v/v) was selected to extract the lipid of the flesh and seed of sea buckthorn. Then, global lipidomic analysis of different varieties of sea buckthorn was conducted. A total of 16 lipid classes and 112 lipid molecular species were determined. Several molecular species, such as PE (phosphatidylethanolamine) 18:1/18:3, PE18:0/18:1, PE18:0/18:2, etc. were selected as the potential biomarkers to classify the samples. Our study provides a scientific basis for quality control of sea buckthorn and promotes the development of sea buckthorn oil.


Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated irinotecan derivative as potential antitumor agent.
A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and synthesized as antitumor agent. Antitumor activity screening assay indicated that BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC50 of 1.83 ± 0.09 μM, 3.95 ± 0.16 μM and 0.68 ± 0.04 μM, respectively, while it displayed better in vivo antiproliferation activity than irinotecan and NKTR-102 in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The action mechanism of BGC0222 was then investigated by integrin-binding competition (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which indicated that BGC0222 may exert antitumor activity by binding to αvβ3 target and consequently inducing neovascularization effect. Pharmacokinetic analysis showed that BGC0222 could slowly and steadily release irinotecan, which was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the whole blood.


[Secondary glaucoma in childhood uveitis].
Ocular hypertension and secondary glaucoma are frequent and challenging complications in childhood uveitis. They are commonly found in patients with panuveitis or anterior uveitis and are often associated with juvenile idiopathic arthritis. Angle closure is rare, while secondary open angle glaucoma accounts for the majority of cases and often continues after the acute inflammation has healed. Monitoring should include tonometry, perimetry, and the objective assessment of the optic disc and nerve fibre layer. First-line therapy should consist of topical carbonic anhydrase inhibitors, followed by beta blockers, and then the alpha-2 agonists. Topical therapy must be monitored closely, as drug-related systemic side effects may preferentially occur in children. Because topical therapy in children is commonly ineffective, surgical interventions are often required. Reports on the use of trabeculectomy, goniosurgery, glaucoma drainage devices, and cyclodestructive procedures show higher failure rates than when used for primary open angle glaucoma in adults.


[Development of a competitive enzyme immunoassay for factor VIII-related antigen].
An enzyme immunoassay system basing on a competitive method has been developed to measure factor VIII related antigen (F. VIII R:Ag). A sufficient discrimination at low F. VIII R:Ag concentrations was gained. This method appears to be sensitive to 7,8 X 10(-3) U/ml F. VIII R:Ag showing an intraassay coefficient of variation (CV) of 0,11. In comparison to the commonly used Laurell electroimmunodiffusion assay for factor VIII significant less antisera per sample for the enzyme immunoassay technique is necessary.


Affective disorders in university student psychiatric patients.
Two hundred and sixty-four student psychiatric referrals were evaluated by the same interviewer using a detailed, precoded questionnaire based on the diagnostic critieria of Feighner et al. (1972). Female sex was associated with secondary and unipolar primary affective disorders. Greater age (over 23 years) was associated with the unipolar primary affective disorder. Race and marital status were not associated with affective disorders.


[Clinical and immunological correlations in patients with disseminated encephalomyelitis and persistent herpes infection].
The analysis of immunological indices in patients with disseminated sclerosis was carried out. The patients presented clinically signs of active and chronic herpes infection. Anamnestic and clinical data were compared against the type of virus. Clinical and immunological correlations depending on the type of dominant herpes infection were detected in the study.


Characterizing molar mass distributions and molecule structures of different chitosans using asymmetrical flow field-flow fractionation combined with multi-angle light scattering.
We investigated various chitosan types and batches successfully with a combination of asymmetrical flow field-flow fractionation and multi-angle light scattering using a customized separation method. Advantageous were the separation capability of a broad applicable molar mass range, the injection of unpurified solutions and the determination of absolute molar masses. Most of the measured samples followed molar mass distributions of monomodal logarithmic Gaussian type. Only one sample showed a very broad distribution caused by either high molar mass amounts or aggregate formation. It was also found that batch-to-batch variations were quite high, which is a common problem for nature-derived products. Thus, especially pharmaceutical products and semi-synthetic derivates should benefit from the development of products with a predictable average molar mass and a narrow distribution. On the basis of received data for each slice eluting from the channel, molar mass-gyration radius relationships could be generated for every single measurement. The hereof received molecule structure parameters were verified to be molar mass dependent, ranging from open structures of rinsed thoroughly molecules to theta coil conditions or an even more compact conformation.


Time-of-flight mass spectrometry in screening serum-specific protein in patients with scrotal Paget's disease.
The weak cationic chip (WCX2) and the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used to test the serum differential proteins in 20 healthy persons, 20 patients with chronic scrotal eczema, and 30 patients with scrotal Paget's disease and test the specificity and sensitivity of screening scrotal Paget's disease with differential proteins. We found that the differences between the 5 protein peaks of the normal group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da were statistically significant (P < .01) and the difference of 3 protein peaks between the scrotal eczema group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da was statistically significant (P < .05). SELDI-TOS-MS technique has certain application value in the early diagnosis of the scrotal Paget's disease and screening for the specific tumor markers.