Immune response during acute Chandipura viral infection in experimentally infected susceptible mice.
Age dependent susceptibility was observed in Chandipura virus (CHPV) infected mice through intravenous and intraperitoneal route. Adult mice were susceptible only through intracerebral route of infection. Immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. As Chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during peripheral infection in young susceptible mice needs to be studied. Through intravenous route of infection the virus produces vireamia and cross the blood brain barrier (BBB) to replicate in the central nervous system. Circulating virus is effectively cleared by virus specific IgM antibody but replication in CNS continues. The infected mice secreted significant amount of proinflammatory cytokines like TNFalpha and MCP-1 and high amount of IFNgamma, IL-1 and IL-6 at 24 h post infection. Reduction in significant amount of CD4, CD8 and CD19 positive cells at 72 h post infection (p < 0.000) was observed in infected mice. Suppression of T cell proliferation of splenocytes to Con A (p < 0.000), LPS and specific antigen was also observed. Presence of preformed virus specific antibody in the form of passive immunization completely protected the mice but immunization on the day or after the virus infection could not completely protect the mice. Proinflammatory cytokines at 24 h post infection and reduction of CD4, CD8 and CD19 positive immune cells might make the mice immune compromised during infection. These cytokines might also increase the permeability of BBB to allow the virus to enter into CNS. Virus replication in CNS is responsible for neurological symptom and mortality. Once virus gets established in CNS it is difficult to protect the mice by passive immunization.


Does resident involvement impact post-operative complications following primary total knee arthroplasty? An analysis of 24,529 cases.
Little is known about the impact of resident involvement on complication rates following total knee arthroplasty (TKA). The goal of our study was to determine the impact of resident involvement on complications following primary TKA. Using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database (2005-2012) we identified 24,529 patients who underwent primary TKA. Of these, 5960 (24.3%) had a resident involved in a primary TKA. Using a multivariate logistic regression which incorporated propensity score adjustment, no differences were seen in morbidity and mortality following those cases with resident involvement (OR: 1.15, P = 0.129). In the first large scale, comprehensive analysis of resident impact on short-term morbidity and mortality, no increase in complications was observed with resident involvement in primary TKA.


Efficient welding of silver nanowire networks without post-processing.
Silver nanowire (AgNW) random meshes have attracted considerable attention as flexible and high-performance transparent electrodes. Notably, post-treatment of the AgNW random meshes, such as thermal annealing, is usually required to guarantee comparable optical transparency and electrical conductivity to commercial indium tin oxide (ITO). Here, the integral elements of preparing a high-performance, large-area AgNW random mesh network are discussed. High-performance nanostructured transparent electrodes can be obtained without any post-treatment, thereby relieving the restrictions related to the substrate. Solvent washing and a large-area spray-coating method effectively reduce the wire-wire contact resistances, thus reducing or eliminating the requirement for post-treatment.


Altered brain and pituitary androgen metabolism by prenatal, perinatal or pre- and postnatal finasteride, flutamide or dihydrotestosterone treatment in juvenile male rats.
1. The authors investigated the administration of finasteride, a 5 alpha-reductase inhibitor; flutamide, an androgen receptor blocker and; exogenous dihydrotestosterone (DHT) during intervals covering different portions of the "critical period" of neural development (i.e. prenatal, perinatal or pre- and postnatal development) to determine the long-term effects of these agents on altering androgen metabolism in hypothalamic and pituitary tissue of juvenile (30 day-old) male rats. 2. The efficacy of the treatments and hypothalamic-pituitary axis function was monitored by measuring luteinizing hormone levels by radioimmunoassay. 5 alpha-Reductase and aromatase activity was determined in hypothalamic and pituitary tissue. 3. Significant alterations in pituitary 5 alpha-reductase activity was detected in DHT-treated animals, whereas, hypothalamic 5 alpha-reductase activity was significantly decreased by finasteride treatment and significantly increased by DHT treatment. Hypothalamic aromatase activity was significantly decreased in flutamide-treated animals. 4. These results suggest that: a) prenatal exposure to exogenous DHT stimulates hypothalamic (but inhibits pituitary) 5 alpha-reductase activity long-term and b) basal 5 alpha-reductase activity levels can be inhibited by finasteride treatment in hypothalamic but not in pituitary tissue, suggesting that a different regulatory mechanism exists for 5 alpha-reductase in hypothalamic versus pituitary tissue.


Reactivity of a biomimetic W(iv) bis-dithiolene complex with CO2 leading to formate production and structural rearrangement.
A mononuclear W(iv) bis-dithiolene complex stabilized by an oxo ligand shows a reductive reactivity toward CO2, from which formate and a dinuclear W(v) complex are generated. An unusual structural rearrangement was observed during the reaction. Structural and spectroscopic characterization for a novel triply bridged dinuclear W(v) complex is reported.


Molecular analysis of Chinese oesophageal squamous cell carcinoma identifies novel subtypes associated with distinct clinical outcomes.
Oesophageal squamous cell carcinoma (ESCC) is a highly heterogeneous cancer with a distinct incidence and prognosis. Molecular events driving ESCC subtypes and prognosis have not been established, and little is known regarding Chinese ESCC patients in Xinjiang, China. Here, we first integrated the genomic and transcriptomic data of 125 Chinese ESCC patients from Xinjiang Tumor Hospital (Urumqi, China). Two independent datasets of GSE53624 and The Cancer Genome Atlas (TCGA) ESCC were used to confirm the results of this study. DNA mutation and overall survival (OS) were analysed independently in the Chinese ESCC cohorts. Genomic analyses revealed a consistent mutation signatures and discordance among mutated genes across the different ESCC cohorts. In addition, transcriptomic profiling identified three Chinese ESCC subtypes associated with clinical and molecular attributes, including patient survival, lymph node status and genetic profile. Moreover, Chinese ESCC subtypes have distinct metabolic, inflammatory, metastatic, and cell proliferation features and unique potential therapeutics. Furthermore, the expression of cell cycle- and/or cell proliferation-related genes was higher in cyclin D1 (CCND1)-amplified tumours than in CCND1-normal tumours from Chinese ESCC patients, suggesting that CCND1 amplification promoted cell proliferation. Our findings provide a framework to facilitate the rational categorization of ESCC in Chinese patients and a foundation for new therapies. This study was supported by the Research Fund of Key Laboratory of Xinjiang oncology (Grant no.2017D04006) and the Outstanding Youth Science and technology training project fund of Xinjiang, China (Grant no. 2017Q058).


High-sensitivity cardiac troponin, a cardiac marker predicting death in patients with kidney disease: a dose-response meta-analysis of cohort studies.
Patients with kidney disease are at increased risk of adverse mortality events. Numerous studies have demonstrated the positive association of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) with all-cause and cardiovascular (CV) mortality in patients with kidney disease; however, the dose-response meta-analysis has not been reported. We therefore performed this study to evaluate the dose-response associations of hs-cTn with risk of all-cause and CV mortality to improve risk stratification. We searched three databases (PubMed, Embase and Web of Science) to identify relevant prospective cohort studies published up to 12 January 2021. Random-effects models were used to summarize relative risks (RRs) and 95% confidence intervals (CIs) of all-cause and CV mortality. Restricted cubic splines were used to fit the dose-response associations. For each 10 ng/l increase in hs-cTnT and hs-cTnI, the risk increased by 14% (RR = 1.14, 95% CI, 1.10-1.18) and 19% (RR = 1.19, 95% CI, 1.09-1.31) for all-cause mortality, 25% (RR = 1.25, 95% CI, 1.13-1.38) and 19% (RR = 1.19, 95% CI, 1.10-1.29) for CV mortality. A linear trend was found between hs-cTnT and all-cause mortality, whereas a non-linear trend was found in hs-cTnI. Additionally, both hs-cTnT and hs-cTnI were shown to have linear trends with CV mortality. Our meta-analysis suggests that hs-cTn had high sensitivity in predicting mortality events. All dose-response trends were rising rather than falling, conferring that any increase in the levels of hs-cTn may possibly predict a death prognosis among chronic kidney disease patients.


Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae Cirrhosae.
The primary objective of this study is to evaluate the antitussive, expectorant and anti-inflammatory effects of alkaloids imperialine (I), chuanbeinone (II), verticinone (III), and verticine (IV), which were isolated from the Bulbus Fritillariae Cirrhosae (BFC) using phytochemical method. The results showed that all the alkaloids significantly inhibited cough frequency and increased latent period of cough in mice induced by ammonia. Besides, imperialine(I), verticinone(III) and verticine(IV) markedly enhanced mice's tracheal phenol red output in expectorant evaluation, and imperialine(I), chuanbeinone(II) significantly inhibited the development of ear edema in a dose-dependent manner in anti-inflammatory assessment. Moreover, important differences were found among the structure-activity relationships for the four alkaloids. These results confirmed that the four alkaloids imperialine, chuanbeinone, verticinone and verticine may be the active ingredients of the Bulbus F. Cirrhosae (BFC).


Toxicity evaluation of Pinus radiata D.Don bark wax for potential cosmetic application.
Radiata pine bark is a widely available organic waste, requiring alternative uses due to its environmental impact on soil, fauna, and forest fires. Pine bark waxes could be used as cosmetic substitutes, but their toxicity requires evaluation since pine bark may contain toxic substances or xenobiotics, depending on the extraction process. This study evaluates the toxicity of radiata pine bark waxes obtained through various extraction methods on human skin cells grown in vitro. The assessment includes using XTT to evaluate mitochondrial activity, violet crystal dye to assess cell membrane integrity, and ApoTox-Glo triple assay to measure cytotoxicity, viability, and apoptosis signals. Pine bark waxes extracted via T3 (acid hydrolysis and petroleum ether incubation) and T9 (saturated steam cycle, alkaline hydrolysis, and petroleum ether incubation) exhibit non-toxicity up to 2% concentration, making them a potential substitute for petroleum-based cosmetic materials. Integrating the forestry and cosmetic industries through pine bark wax production under circular economy principles could promote development while replacing petroleum-based materials. Extraction methodology affects pine bark wax toxicity in human skin cells due to the retention of xenobiotic compounds including methyl 4-ketohex-5-enoate; 1-naphthalenol; dioctyl adipate; eicosanebioic acid dimethyl ester; among others. Future research will investigate whether the extraction methodology alters the molecular structure of the bark, affecting the release of toxic compounds in the wax mixture.


[Formula: see text]Multivariate base rates of score elevations on the BRIEF2 in children with ADHD, autism spectrum disorder, or specific learning disorder with impairment in reading.
There is a paucity of research examining multivariate base rates (MBRs) of elevated scores in pediatric rating scales of cognition. We present novel MBR information on the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) for several clinical groups: Attention-Deficit/Hyperactivity Disorder Combined Presentation (ADHD-C); ADHD Inattentive Presentation (ADHD-I); Autism Spectrum Disorder (ASD); and Specific Learning Disorder with impairment in Reading (SLD-R). Participants included children diagnosed as having ADHD-C (n = 350), ADHD-I (n = 343), ASD (n = 390), or SLD-R (n = 240). Cumulative MBRs (e.g., the % of a sample having one or more elevated scores) were examined for each BRIEF2 form (Parent, Teacher, and Self-Report) and at three T-score cutoffs (T ≥ 60, T ≥ 65, and T ≥ 70). The MBR of obtaining at least one elevated score was common across clinical groups and forms at T ≥ 60 (ADHD-C = 90.5-98.1%; ADHD-I = 83.9-98.7%; ASD = 90.3-96.9%, SLD-R = 60.0-78.4%), T ≥ 65 (ADHD-C = 66.7-97.2%; ADHD-I = 77.5-94.9%; ASD = 77.3-92.7%; SLD-R = 38.5-64.0%), and T ≥ 70 (ADHD-C = 52.4-89.4%; ADHD-I = 64.8-84.2%; ASD = 54.5-83.2%; SLD-R = 26.9-44.1%). MBRs appeared to differ as a function of group (ADHD-C > ADHD-I > ASD > SLD-R) and form (Parent > Teacher > Self-Report) though future research with well-defined samples is needed to investigate this. We provide novel MBR information to enhance clinical interpretation of BRIEF2 data.


The impact of indigenous soil yeasts inoculation on bean (Phaseolus vulgaris) growth.
To determine whether the use of soil yeasts as inoculum would intervene in improving bean (Phaseolus vulgaris) growth and its symbiotic parameters, various experiments have been carried out. The effect of inoculation by soil yeasts Meyerozyma guilliermondii GP MT258984, Debaryomyces hansenii DFA MT259039, Rhodotorula mucilaginosa LIA MT259358, Rhodotorula mucilaginosa LC MT252049, along with the strain Saccharomyces cerevisiae in their cell or metabolite forms, was investigated in non-sterile (sand) and agricultural substrates (soil), in association or not with mycorrhizal fungi. The results showed that the yeast could have a beneficial effect on the bean biomass directly without increasing its nodulation and mycorrhization, or indirectly by improving those symbiotic parameters. They also revealed a very important ecological aspect and the possibility of inoculating with indigenous soil yeasts to increase the number of fertilising microorganisms, such as mycorrhizae and rhizobia, without resorting to introducing exogenous strains.


Measurement Instruments of Productivity Loss of Paid and Unpaid Work: A Systematic Review and Assessment of Suitability for Health Economic Evaluations From a Societal Perspective.
This study aimed (1) to perform a systematic literature review of instruments for measuring productivity loss of paid and unpaid work and (2) to assess the suitability (in terms of identification, measurement, and valuation) of these instruments for use in health economic evaluations from a societal perspective. Articles published from 2018 were sourced from PubMed/Medline, PsycInfo, Embase, and Econlit. Using 2 separate search strategies, eligible economic evaluations and validation studies were selected and unique measurement instruments identified. A data-extraction form was developed by studying previous literature and consulting an international panel of experts in the field of productivity costs. This data-extraction form was applied to assess the suitability of instruments for use in economic evaluations. A total of 5982 articles were retrieved from the databases, of which 99 economic evaluations and 9 validation studies were included in the review. A total of 42 unique measurement instruments were identified. Nine instruments provided quantified measures of absenteeism, presenteeism, and unpaid work. Five instruments supplied the necessary information to enable the use of at least 1 common valuation method. The Health and Labour Questionnaire-Short Form, Health and Labour Questionnaire, and Institute for Medical Technology Assessment Productivity Cost Questionnaire met both criteria. Nevertheless, the developers replaced the Health and Labour Questionnaire-Short Form and Health and Labour Questionnaire by the more recently developed Institute for Medical Technology Assessment Productivity Cost Questionnaire. Although many instruments for measuring productivity loss were identified, most were not suitable for capturing productivity changes for economic evaluations from a societal perspective. Future research can benefit from this study by making an informed instrument choice for the measurement of productivity loss of paid and unpaid work.


[Acute hepatocytic necrosis during ketoconazole therapy for treatment of onychomycosis. National Foundation for Registry and Evaluation of Adverse Effects].
The imidazole derivative ketoconazole is approved in the Netherlands for treatment of local and systemic fungal infections. Despite the risk of major hepatic damage, this antimycotic drug is still being used in daily practice for the oral treatment of patients with onychomycosis. Since April 1986, 18 cases of relatively severe hepatic damage in the Netherlands were ascribed to the oral use of ketoconazole for the treatment of onychomycosis, skin infection or vaginal candidiasis. Given the potential risk for the patients concerned, ketoconazole should no longer be prescribed for relatively mild cosmetic disorders such as onychomycosis.


Inflammation-based Scores are Associated with the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage After Neuro-intervention.
Prognostic significance of inflammatory response has been reported in various diseases. The objective of this study was to analyze the association between inflammation- based scores and the prognosis of patients who underwent neuro-intervention for aneurysmal subarachnoid hemorrhage (SAH). Inflammation-based scores such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) were analyzed for aneurysmal SAH patients who underwent endovascular intervention. Unfavorable functional outcome was defined as a modified Rankin Scale (mRS) score of 3-6. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off values of inflammation- based scores for predicting unfavorable functional outcome. Logistic regression analyses were performed to explore the relationship between inflammation-based scores and the prognosis of patients. A total of 498 patients were enrolled. Optimal cutoff values of inflammation-based scores of NLR, LMR, and MHR for unfavorable functional outcome were 5.7, 4.2, and 1.5, respectively (p < 0.001, < 0.001, and 0.004, respectively). In multivariate analysis, NLR value ≥ 5.7 (odds ratio [OR] 1.92, 95% CI 1.42-3.42; P = 0.008), LMR value < 4.2 (OR 1.74, 95% CI 1.48-2.98; P = 0.018), and MHR value ≥ 1.5 (OR 1.44, 95% CI 1.22-2.82; P = 0.040) were independently associated with unfavorable functional outcome. Inflammation based scores were associated with functional outcome after endovascular intervention for aneurysmal SAH. Higher NLR and MHR with lower LMR could predict unfavorable outcomes of aneurysmal SAH patients who underwent endovascular intervention.


Proteomic analysis of soluble protein extract of adult Toxocara cati.
Toxocara cati is a cat roundworm and the causative agent of toxocariasis as a cosmopolitan zoonotic disease. As no information has been reported so far, identification of T. cati proteins can be useful for the development of new diagnostic strategies. This study was conducted to identify the major proteins in the adult T. cati tegument using bi-dimensional electrophoresis (2-DE) and shotgun proteomics. A total proteins were identified, among them the metabolic enzymes were the largest group, including: Enolase, triose phosphate isomerase, fructose-bisphosphate aldolase, aldehyde dehydrogenase. The other important protein groups recognized in T. cati, belong to the HSP-family, the structure and motor proteins, such as actin. The role of these proteins have been implicated in parasite-host interactions and modulating cellular immune response, immune regulation in evasion mechanisms of the host immune response. Characterizing T. cati adult proteins play a key role not only in host-parasite interactions, but also in the discovery of drug targets, subunit vaccines against toxocariasis, immunodiagnostic kits for toxocariasis and the identification of novel immuno-modulators that can form the next generation of therapeutic possibilities for inflammatory diseases.


Photoperiodism and the photic environment of the pitcher-plant mosquito, Wyeomyia smithii.
Wyeomyia smithii Coq. (Diptera: Culicidae) overwinters as a larva in a state of diapause which is initiated, maintained, and terminated by photoperiod. Both in the dawn and in the dusk, diapausing larvae are photoperiodically most sensitive to blue light (390-450 nm) with a shoulder in response in the bluegreen and green (480-540 nm) region of the spectrum. The saturation curves for response to blue light in the dusk has a steeper slope than for response to blue-green and green light in the dusk, suggesting two distinct pigments or pigment complexes underly photoperiodic response in W. smithii.The photic environment of W. smithii during twilight is rich in yellow-green light but sufficient light is available at 390-540 nm to trigger photoperiodic response early during morning civil twilight and to sustain response until late in evening civil twilight. Comparison of action spectra with spectra of available light indicates that the zenith angles of the sun which would result in 50% response are 95°48' and 94°52' in the dawn and dusk, respectively. Using these zenith angles to approximate daylength in nature provides a resonable prediction of development in the field.The flux density of photons necessary to elicit 50% development a 454 nm is about 9×107 photons/cm2 s in the dawn and 3×108 photons/cm2 s in the dusk. This high degree of sensitivity enables W. smithii to cue to the rapidly changing light intensity which occurs around the nautical-civil twilight transition. At the same time, the chromophore is not likely to be stimulated by the light of the full moon.


Snail populations, beech litter production, and the role of snails in litter decomposition.
The population densities of snails living in beech litter were studied form March 1968 to April 1969. Litter production over one year was measured and the role of snails in litter disappearance assessed.Snails were extracted from litter using a modified Vágvölgyi (1952) flotation method, extraction efficiencies being 84%. The mean annual population density of the twenty-one species of snail recorded on the main sampling site was estimated at 489/m2. Carychium tridentatum was the most numerous species, with a mean density of 200/m2. Acanthinula aculeata, Punctum pygmaeum and Vitrea contracta also had fairly high mean densities. The mean annual biomass was 699 mg dry wt./m2 or 278 mg ash-free dry wt./m2. Hygromia striolata and Oxychilus cellarius/alliarius were the most important species in terms of biomass on the main site. Within the limits of accuracy imposed by the sampling regime the population densities of four out of five of the species (C. tridentatum, A. aculeata, V. contracta, Retinella pura) studied remained unchanged throughout the year, whereas P. pygmaeum had a significantly higher autumn population. C. tridentatum populations were highly aggregated at all times of the year, most markedly so in June. Other species were aggregated at certain times of the year only. Samples taken from other sites showed total population densities of snails ranging from 185-1082 snails/m2.A total tree litter production of 652 g/m2/annum was recorded of which 584g/m2/annum was of beech material. 72% fell in the October-December period. 58% of the beech litter-fall was leaves, 5.2% bud-scales, 27% fruits and 10% twigs and bark. Summation of appropriate field layer peak standing crops amounted to 23.3 g/m2. This was considered as potential litter and was equivalent to 3.4% of the total litter input. The litter standing on the woodland floor in Septermber 1968 was 2,700 g/m2, hence, assuming a steady state, litter turnover time was estimated as 4.5 years.It was calculated that the total snail population ingested 0.35-0.43% of the annual litter input, of which 49% was assimilated. The role of the individual species is examined in relation to concepts of "key species" in ecosystem functioning. The possible role of slugs in decomposition processes is also discussed.


The role of genetic and autoimmune factors in premature ovarian failure.
To identify the role of both genetic (number of CGG repeats in the FMR1 gene) and autoimmune factors (anti-ovarian antibodies) in premature ovarian failure (POF). In cross-sectional study, 78 women with POF were divided into 3 groups by the number of CGG repeats (less than 28, 28-36, more than 36) in any of the FMR1 gene alleles. We performed the detection of skewed X-chromosome inactivation, CGG repeats in the FMR1 gene, anti-ovarian antibodies (AOA) and sex hormones tests. Compared to a higher or lower number of CGG repeats the 28-36 triple CGG counts are strongly associated with the AOA detection (RR = 19.23, 95% CI = 2.63-100.0). The women with autoimmune-driven POF have significantly higher anti-Mullerian hormone levels in comparison to women with non-autoimmune-driven POF. The presence of AOA above 10 IU/mL is associated with the normal number of CGG repeats in regard to ovarian reserve and a better preservation of follicular primordial pool in the women with POF.


Affective and somatic aspects of spontaneous and precipitated nicotine withdrawal in C57BL/6J and BALB/cByJ mice.
The aversive aspects of nicotine withdrawal are powerful motivational forces contributing to the tobacco smoking habit. We evaluated measures of affective and somatic aspects of nicotine withdrawal in C57BL/6J and BALB/cByJ mice. Nicotine withdrawal was induced by termination of chronic nicotine delivery through osmotic minipumps or precipitated with the nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine or dihydro-beta-erythroidine (DHbetaE). A rate-independent discrete-trial intracranial self-stimulation threshold procedure was used to assess brain reward function. Anxiety-like behavior and sensorimotor gating were assessed in the light-dark box and prepulse inhibition (PPI) tests, respectively. Acoustic startle response and somatic signs of withdrawal were also evaluated. Spontaneous nicotine withdrawal after 14-day exposure to 10-40 mg/kg/day nicotine induced no alterations in anxiety-like behavior, startle reactivity, PPI, or somatic signs in either strain, and no changes in thresholds in C57BL/6J mice. Extended 28-day exposure to 40 mg/kg/day nicotine induced threshold elevations, increased somatic signs, and anxiety-like behavior 24 h post-nicotine in C57BL/6J mice; thresholds returned to baseline levels by day 4 in nicotine-exposed mice. Mecamylamine or DHbetaE administration induced threshold elevations in nicotine-exposed C57BL/6J mice compared with saline-exposed mice. In conclusion, administration of relatively high nicotine doses over prolonged periods of time induces both the affective and somatic aspects of spontaneous nicotine withdrawal in the mouse, while exposure to nicotine for shorter periods of time is sufficient for nAChR antagonist-precipitated nicotine withdrawal. The current study is one of the first to demonstrate reward deficits associated with both spontaneous and nAChR antagonist-precipitated nicotine withdrawal in C57BL/6J mice.


[Construction of the French concept of spirituality].
"Laïcité"--the French concept of secularity--holds a central position in contemporary debates. The subject here is a reminder of how this concept was introduced in France, how it has guided the secularization process in institutions and on what levels it is now called into question.


Bioenergetics and food preferences in sympatric southern Chilean rodents.
Ecological divergences in two congeneric sympatric woodland rodents, Akodon olivaceus brachiotis and Akodon longipilis apta (Family Cricetidae) was demonstrated from determination of energetic bud gets and food preferences. It was found that each species posseses a different bioenergetic strategy. The heavier (A. longipilis) species has a larger daily energetic budget as compared to the lighter one (A. olivaceus). This phenomenon can be partially explained by their differential selection of seeds.Finally, it is hypothesized that these ecological differences could be important in enabling the coexistence for these species.


HOX cluster-embedded antisense long non-coding RNAs in lung cancer.
Homeobox (HOX) genes play vital roles in embryonic development and oncogenesis. In humans, there are 39 HOX genes found in four clusters that are located on different chromosomes. The HOX clusters also contain numerous non-protein-coding RNAs, including some lncRNAs. The HOX cluster-embedded lncRNAs (HOX-lncRNAs), most notably, HOTTIP and HOTAIR play a major role in the regulation of their adjacent coding genes. Recently, most HOX-lncRNAs have been shown to impact tumorigenesis and cancer progression. Several HOX-lncRNAs, including HOTTIP, HOXA11-AS, HOTAIRM1, HOXA-AS3, HOXA10-AS, HOTAIR, and HAGLR, are dysregulated in lung cancer. Moreover, their expression levels are correlated with the clinical features of this disease. These HOX-lncRNAs regulate the proliferation, invasion, migration, and chemo-resistance of lung cancer cells through various molecular mechanisms. Although lncRNAs have received much attention lately, the functions of some HOX-lncRNAs in the development of cancer are unclear. Thus, HOX-embedded lncRNAs should be widely investigated in cancer. Here, we review the functions of HOX-lncRNAs in lung cancer.


Tick microbiome: the force within.
Ticks are obligate blood-feeders and serve as vectors of human and livestock pathogens worldwide. Defining the tick microbiome and deciphering the interactions between the tick and its symbiotic bacteria in the context of tick development and pathogen transmission will likely reveal new insights and spawn new paradigms to control tick-borne diseases. Descriptive observations on the tick microbiome that began almost a century ago serve as forerunners to the gathering momentum to define the tick microbiome in greater detail. This review will focus on the current efforts to address the microbiomes of diverse ticks, and the evolving understanding of tick microbiomes. There is hope that these efforts will bring a holistic understanding of pathogen transmission by ticks.


Upregulating sirtuin 6 ameliorates glycolysis, EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency.
Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC.Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT01666184.


Effects of GV1001 on Language Dysfunction in Patients With Moderate-to-Severe Alzheimer's Disease: Post Hoc Analysis of Severe Impairment Battery Subscales.
The efficacy and safety of GV1001 have been demonstrated in patients with moderate-to-severe Alzheimer's disease (AD). In this study, we aimed to further demonstrate the effectiveness of GV1001 using subscales of the Severe Impairment Battery (SIB), which is a validated measure to assess cognitive function in patients with moderate-to-severe AD. We performed a post hoc analysis of data from a 6 month, multicenter, phase 2, randomized, double-blind, placebo-controlled trial with GV1001 (ClinicalTrials.gov, NCT03184467). Patients were randomized to receive either GV1001 or a placebo for 24 weeks. In the current study, nine subscales of SIB-social interaction, memory, orientation, language, attention, praxis, visuospatial ability, construction, and orientation to name- were compared between the treatment (GV1001 1.12 mg) and placebo groups at weeks 12 and 24. The safety endpoints for these patients were also determined based on adverse events. In addition to the considerable beneficial effect of GV1001 on the SIB total score, GV1001 1.12 mg showed the most significant effect on language function at 24 weeks compared to placebo in both the full analysis set (FAS) and per-protocol set (PPS) (p=0.017 and p=0.011, respectively). The rate of adverse events did not differ significantly between the 2 groups. Patients with moderate-to-severe AD receiving GV1001 had greater language benefits than those receiving placebo, as measured using the SIB language subscale.


Reduced volume of red blood cell priming is safe for pediatric patients undergoing therapeutic plasma exchange.
Therapeutic Plasma Exchange (TPE) procedures in pediatric patients are challenging due to the large extracorporeal volume of the cell separators, which were designed for adults. Red blood cell (RBC) priming is an alternative for overpassing the risks of hypovolemia, but data referring to the volume of packed RBCs to be infused are yet incomplete. Restricting the volume of RBC priming may potentially be associated with less transfusion reactions. To determine the safety of administering a reduced volume of RBC priming for pediatric patients undergoing TPE, in comparison to the standard volume recommended by the cell separators' manufacturers. This was a case-control study which enrolled 15 pediatric patients undergoing TPE and weighting more than 10Kg. The TPE procedures (n = 406) were divided in two groups: 1) Group1: TPE with ≤150 mL of packed RBC priming and 2) Group2: TPE with 150-250 mL of RBC priming. Groups were compared in terms of hemoglobin / hematocrit and occurrence of adverse reactions. Group1 and Group2 did not differ significantly in relation to pre- and post-TPE hemoglobin (Hb) levels (p = 0.19 and p = 0.18, respectively). The Δ Hb (Hb pre-TPE - Hb post-TPE) was also not statistically different between the groups. The number of adverse reactions was significantly higher in Group 2 in relation to Group 1 (p = 0.01). The number of allergic reactions was also higher in Group 2 (p = 0.06). Restricting the volume of RBC priming to less than 150 mL is safe for pediatric patients weighting more than 10Kg and associated with lower rates of transfusion-related adverse reactions.


Subgingival microbiota in individuals with severe chronic periodontitis.
Subgingival microorganisms are potentially associated with periodontal diseases. However, the correlation between the variance in the periodontal microbiome and the prevalence and severity of periodontitis remains unclear. The aim of this study was to determine the subgingival microbiota in Taiwanese individuals with severe chronic periodontitis (SP). The composition of the subgingival microbiota in healthy and diseased individuals was compared using a 16S rRNA metagenomic approach and quantitative polymerase chain reaction (qPCR). A total of 20 samples, including 10 from healthy individuals and 10 from SP patients, were analyzed. We found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples. Cluster analysis by principal component analysis and heat map showed that the bacterial communities were different in the two groups. Streptococcus dominated across all the healthy samples, whereas Prevotella, Porphyromonas, and Treponema were highly abundant across all diseased samples. At least 13 bacterial genera were conserved among all the samples. Only eight genera, including Lautropia, Parvimonas, Actinomyces, Capnocytophaga, Paludibacter, Streptococcus, Haemophilus, and Corynebacterium, were significantly enriched in the healthy group, and six genera, including Porphyromonas, Treponema, Tannerella, Aggregatibacter, Peptostreptococcus, and Filifactor, were significantly enriched in the diseased group. Furthermore, a trend of abundance of bacteria at the species level measured by qPCR in all samples was consistent with the 16S rRNA metagenomics results. This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics.


Dose distributions in regions containing beta sources: small scale nonuniformities.
An analytic model for the calculation of dose in regions containing slightly nonuniform distributions of beta sources, and a solution for the dose distribution in an infinite, homogeneous medium with a uniform, monoenergetic source distribution and a sinusoidal perturbation of the source are presented.


Neurocritical Care Research: Collaborations for Curing Coma.
One of the most common questions asked by family members of patients with brain injuries who are in a coma is "will my loved one wake up?". Despite substantial improvements in the care of patients with neurological diseases, the medical and scientific community struggles to answer this simple question. More importantly, the technology and treatment strategies to improve the trajectory of patients with impaired consciousness in the acute setting are limited. The Curing Coma Campaign was developed by the Neurocritical Care Society as a multispecialty, multi-interest community of researchers and caretakers who are focused on patients with disorders of consciousness (DoC) in the acute phase of care. Over the first few years of the group, several publications have focused on identifying the gaps in our knowledge to encourage research in the area. In this review, the current understanding of DoC is reviewed. The work of the Curing Coma Campaign to identify gaps in our knowledge is highlighted.


Treatment of atrial fibrillation. Recommendations from a workshop arranged by the Medical Products Agency (Uppsala, Sweden) and the Swedish Society of Cardiology.
Atrial fibrillation may be paroxysmal or chronic. The paroxysmal form presents in the form of attacks of short duration but may last for up to 3-4 days. Episodes of atrial fibrillation of longer duration are considered as chronic. The diagnosis is made by ECG.


Age and heart transplantation: results from a heart failure management unit.
More evidence is needed to assess the pros and cons of maintaining age-limit policies in heart transplantation (HT). We analyzed clinical data from a heart failure management unit to investigate the impact of age on prognosis of two distinct cohorts: (i) 309 patients (median age, 57 yr; 62% male) with severe chronic heart failure (CHF) consecutively screened for HT; (ii) 336 HT recipients (median age 56 yr, 82% male). In CHF patients (screened for HT), prognosis was conditioned by the underlying severity of cardiac disease (i.e., New York Heart Association class III-IV, decreasing blood pressure, presence of atrial fibrillation and severe mitral regurgitation), whereas increasing age showed no sign of predicting all-cause or cardiovascular mortality (both p > or = 0.4). In HT recipients, age did not retain significance at multivariate analysis as an independent predictor (p > or = 0.14 for both all-cause and cardiovascular death), whereas ischemic etiology of pre-existing CHF did (p < or = 0.02). Age did not appear to be a primary determinant of all-cause or cardiovascular mortality among potential HT candidates or eventual recipients (ischemic etiology of CHF turned out to be the major determinant of post-transplant outcome). These results support the concept that HT may be considered a treatment option in patients with more advanced age strata, particularly when affected by non-ischemic cardiomyopathy.


Microbial epidemiology and risk factors for relapse in gram-negative bacteria catheter-related bloodstream infection with a pilot prospective study in patients with catheter removal receiving short-duration of antibiotic therapy.
Infectious Diseases Society of America (IDSA) guidelines suggest 7-14 days' duration of antibiotic treatment for uncomplicated Gram-negative bacteria (GNB) catheter-related bloodstream infection (CRBSI). The objectives of this study were to review microbial epidemiology, to determine rate and risk factors for relapse, and to compare clinical outcomes in patients receiving long- versus short-duration antibiotic therapy. A retrospective phase 1 study was conducted between January 2010 and October 2016 to review microbial epidemiology and to determine the incidence of and risk factors for relapse in patients with GNB CRBSI, according to the IDSA guidelines diagnostic criteria. In phase 2 of the study, patients without risk factors for relapse between November 2016 and October 2017 were prospectively recruited to receive antibiotic therapy for 7 days after catheter removal. Matched patients from the retrospective phase 1 study who had received antibiotic therapy for ≥14 days were selected as a phase 2 control group to compare outcomes. In phase 1, three most common pathogens identified among 174 cases were Pseudomonas aeruginosa (22.0%), Klebsiella pneumoniae (16.7%), and Stenotrophomonas maltophilia (13.4%). Eighty-nine episodes of infection occurred while patients were receiving antibiotic therapy. Of 140 cases, the relapse rate was 6.4%. Catheter retention was the only risk factor strongly associated with relapse (odds ratio = 145.32; 95% confidence interval 12.66-1667.37, P < 0.001). In phase 2, 11 patients with catheter removal were prospectively recruited to receive short-duration therapy. The number of patients with relapse receiving long- or short-duration therapy was 1 (3%) and 0 (0%), respectively (P = 1.000). For the management of patients with uncomplicated GNB CRBSI, empiric broad-spectrum antibiotic therapy with adequate coverage of P. aeruginosa should be chosen. Catheter removal should be performed to prevent relapse and shortening the duration of treatment could be considered. Thai Clinical Trial Registry: TCTR20190914001 . Retrospectively registered on 13 September 2019.


Racial and ethnic disparities in lower extremity amputation: Assessing the role of frailty in older adults.
Frailty is a state of decreased physiologic reserve contributing to functional decline and is associated with adverse surgical outcomes, particularly in the elderly. Racial disparities have been reported previously both in frail individuals and in limb-salvage patients. Our goal was to assess whether race and ethnicity are disproportionately linked to frailty status in geriatric patients undergoing lower-limb amputation, leading to an increased risk of complications. A 3-year analysis was conducted of the National Surgical Quality Improvement Program database and included all geriatric (age ≥65 years) patients who underwent amputation of the lower limb. The frailty index was calculated using the 11-factor modified frailty index with a cutoff limit of 0.27 defined for frail status. Outcomes were 30-day complications, mortality, and readmissions. Multivariate regression analysis was performed. A total of 4,218 geriatric patients underwent surgical amputation of a lower extremity (above knee: 41%; below knee: 59%). Of these patients, 29% were frail, 26% were African American, and 9% were Hispanic. Being African American (odds ratio: 1.6 [1.3-1.9]) and Hispanic (odds ratio: 1.1 [1.05-2.5]) was independently associated with frail status. Frail African Americans had a higher likelihood of 30-day complications (odds ratio: 3.2 [1.9-4.4]) and 30-day readmissions (odds ratio: 2.9 [1.8-3.6]) when compared with nonfrail individuals. Similarly, frail Hispanics had higher 30-day complications (odds ratio: 2.6 [1.9-3.1]) and 30-day readmissions (odds ratio: 1.4 [1.1-2.7]) compared with nonfrail Hispanics/Latinos. African American and Hispanic geriatric patients undergoing lower-limb amputation are at increased risk for frailty status and, as a result, increased associated operative complications. These disparities exist regardless of age, sex, comorbid conditions, and location of amputation. Further studies are needed to highlight disparities by race and ethnicity to identify potentially modifiable risk factors, decrease frailty, and improve outcomes.


Testosterone modulation of anxiety in gonadally-suppressed male rhesus monkeys: a role for gonadotropins?
Testosterone (T) has repeatedly been shown to have anxiolytic properties in rodents, but findings in primates are more mixed. To examine the effects of exogenous T on anxiety, we tested pharmacologically-castrated adult male rhesus monkeys in a modified version of the Human Intruder Paradigm, which measured defensive responses to an unfamiliar human staring directly at them for 2 min. Monkeys were tested at 2 week intervals during 4 experimental conditions lasting 4 weeks each: at baseline, during treatment with the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (200 μg/kg; Lupron phase), during treatment with Lupron+T enanthate (TE, 5 mg/kg; TE phase) and during treatment with Lupron+oil vehicle (oil phase). We found that the number of anxious behaviors was lower during periods of low T (Lupron only and Lupron+oil phases) than during the Lupron+TE phase. No change in pacing or watching behavior was observed. Thus, in contrast to rodent data, we found no evidence for anxiolytic properties of T in male rhesus monkeys. Rather, T supplementation restored baseline levels of anxiety in Lupron-treated monkeys. These discrepant findings may be best explained by the low levels of gonadotropins achieved by the GnRH agonist. We suggest that Lupron-induced luteinizing hormone (LH) suppression reduced anxiety and that this effect was abolished by T administration. This interpretation is consistent with the view that T increases emotional reactivity to a potential threat and facilitates adaptive arousal response in face of immediate social challenge.


Irisin and ALCAT1 mediated aerobic exercise-alleviated oxidative stress and apoptosis in skeletal muscle of mice with myocardial infarction.
Skeletal muscle in patients with heart failure (HF) exhibits altered structure, function and metabolism. Myocardial infarction (MI) is the most common cause of HF. Oxidative stress and cell apoptosis are involved in the pathophysiology of MI/HF-induced skeletal muscle atrophy. It is well recognized that aerobic exercise (AE) could prevent skeletal muscle atrophy after MI, but the underlying mechanism and molecular targets are still not fully clarified. In this study, Fndc5-/- and Alcat1-/- mice were used to establish the MI model and subjected to six weeks of moderate-intensity AE. C2C12 cells were treated with H2O2 and recombinant human Irisin (rhIrisin), or transduced with a lentiviral vector to mediate the overexpression of ALCAT1 (LV-Alcat1). Results showed that MI reduced Irisin expression and antioxidant capacity of skeletal muscle, increased ALCAT1 expression, induced protein degradation and cell apoptosis, which were partly reversed by AE; Knockout of Fndc5 further aggravated MI-induced oxidative stress and cell apoptosis in skeletal muscle, and partly weakened the beneficial effects of AE. In contrast, knockout of Alcat1 reduced MI-induced oxidative stress and cell apoptosis and strengthened the beneficial effects of AE. rhIrisin and AICAR intervention inhibited ALCAT1 expression, oxidative stress and cell apoptosis, which induced by H2O2 or LV-Alcat1 in C2C12 cells. These findings reveal that AE could alleviate the levels of oxidative stress and apoptosis in skeletal muscle following MI, partly via up-regulating Irisin and inhibiting ALCAT1 expression.


Deciphering molecular mechanisms of arginine deiminase-based therapy - Comparative response analysis in paired human primary and recurrent glioblastomas.
Arginine auxotrophy constitutes the Achilles' heel for several tumors, among them glioblastoma multiforme (GBM). Hence, arginine-depleting enzymes such as arginine deiminase (ADI) from Streptococcus pyogenes are promising for treatment of primary and maybe even refractory GBM. Based on our previous study in which ADI-susceptibility was shown on a panel of patient-derived GBM cell lines, we here aimed at deciphering underlying molecular mechanisms of ADI-mediated growth inhibition. We found that ADI (35 mU/mL) initially induces a cellular stress-response that is characterized by upregulation of genes primarily belonging to the heat-shock protein family. In addition to autophagocytosis, we show for the first time that senescence constitutes another cellular response mechanism upon ADI-treatment and that this bacterial enzyme is able to act as radiosensitizer (¼ cases). Long-term treatment schedules revealed no resistance development, with treated cells showing morphological signs of cell stress. Next, several combination strategies were employed to optimize ADI-based treatment. Simultaneous and sequential S. pyogenes ADI-based combinations included substances acting at different molecular pathways (curcumin, resveratrol, quinacrine, and sorafenib, 2 × 72 h treatment). Adding drugs to GBM cell lines (n = 4, including a matched pair of primary and recurrent GBM in one case) accelerated and potentiated ADI-mediated cytotoxicity. Autophagy was identified as the main cause of tumor growth inhibition. Of note, residual cells again showed classical signs of senescence in most combinations. Our results suggest an alternative treatment regimen for this fatal cancer type which circumvents many of the traditional barriers. Using the metabolic defect in GBM thus warrants further (pre-) clinical evaluation.


[Elimination of syngeneic lymphoma cells from a mouse bone marrow suspension using immune cytotoxic lymphocytes sensitized in vitro].
Murine splenocytes were cultivated with syngenic EL-4 lymphoma cells in the presence of interleukin-2 to obtain cytotoxic antileukemic lymphocytes. It was shown that the use of cytotoxic lymphocytes helped killing completely syngenic lymphoma cells in the mixture of bone marrow and EL-4 cells, spleen colony-forming hemopoietic predecessor cells being retained.


Role of gastric acid in the aetiology of dyspeptic disease and dyspepsia.
The main diseases associated with dyspepsia are peptic ulcer disease, gastro-oesophageal reflux disease and non-ulcer dyspepsia. Increased gastric acid secretion is a characteristic of most duodenal ulcer patients and of a small minority of non-ulcer dyspepsia and gastro-oesophageal reflux disease patients. Although acid secretion is normal in most gastro-oesophageal reflux disease patients, the condition is mainly the result of excess exposure of the distal oesophagus to acid refluxing from the stomach. Increased mucosal sensitivity to acid is involved in the aetiology of dyspeptic symptoms in the majority of patients with peptic ulcer disease and gastro-oesophageal reflux disease, and in a minority of non-ulcer dyspepsia subjects. Gastric acid, therefore, plays an important role in both the aetiology of dyspeptic diseases and in the aetiology of dyspeptic symptoms.


Topical treatment with sulfur 10 per cent for rosacea.
In a controlled study, topical treatment with sulfur 10 per cent is shown to be equally effective as orally given tetracycline in the management of rosacea.


[Left flank tumor of fluctuating size in a 5-week-old boy: perirenal urinoma caused by urethral valves].
Flank swelling and pseudotumors of the kidney are unusual manifestations of obstructive uropathies in small children. Our case illustrates typical problems and briefly reviews management options. A 5-week-old boy presented with a large, palpable urinoma due to posterior urethral valves. Sonography and voiding cystourethrogram led to the diagnosis and immediate suprapubic transcutaneous urinary diversion was performed. However, the urinoma did not resolve. Thus, in addition to suprapubic urinary diversion, indirect drainage - instead of percutaneous puncture - was performed by retrograde insertion of a double-J catheter. Urethral valves were resected 4 weeks later and follow-up demonstrated an uneventful further development with normal renal function as assessed by regular ultrasound studies, a repeat cystourethrogram and a renal scan. Perirenal urinomas may be the first symptom in patients with posterior urethral valves. Drainage via double-J stenting offers a promising alternative to percutaneous puncture. A renoprotective "pop-off" mechanism by which intrarenal pressure may be relieved is discussed.


Coexisting adenocarcinoma and malignant lymphoma of the stomach: case report and review of the Japanese literature.
After a diagnosis of advanced carcinoma, a 77-yr-old female underwent gastrectomy. A 6 X 5 cm ulcerative mass in the angle was shown to be differentiated adenocarcinoma in the surrounding wall, and malignant lymphoma in the bottom. Carcinomatous infiltration was limited to the muscularis mucosae. Neither generalized lymphoma nor locoregional lymph node metastasis of either neoplasm was noted. A survey of 35 Japanese patients, including our own case with the two coexistent neoplasms in the stomach, revealed that the male-to-female ratio was 2.3:1, with no significant difference between the mean age of the sexes. The prevalence of adenocarcinoma in its early stage (60% of 35 patients) and of a histologically differentiated type (85% of 27 patients) of adenocarcinoma is quite different from that of usual Japanese gastric carcinoma, and it may suggest that there are some factors influencing the coexistent development of both neoplasms.


Clinical importance of circulating immune complexes in human acute lymphoblastic leukemia.
A total of 122 sera from acute lymphoblastic leukemia (ALL) patients were analyzed for circulating immune complexes (CIC) by two methods: the 125I-Clq binding assay and the polyethylene glycol precipitation test (PEG). The results were correlated with induction, remission and relapse stages of the disease. Using the first method the levels of CIC in induction were 15.18 +/- 9.15, with 19/29 positive cases (65.50%), P less than 0.001 compared with controls. In the remission phase the levels were 9.02 +/- 5.62, 11/45 (24.49%) nonsignificant P value, and in relapse they were 16.14 +/- 11.17 28/48 (58.33%) P less than 0.001. The PEG precipitation test results were: 0.33 +/- 0.10, 8/22 (36.36%); 0.24 +/- 0.11, 10/48 (20.83%) and 0.28 +/- 0.10, 6/28 (21.42%), respectively. Thus the values of CIC as measured by PEG in the three clinical of phases ALL did not differ significantly from controls. This contrasts with results obtained by the radioiodinated C1q binding assay, where the incidence of positive values was significantly higher in induction and in relapse and lower in the remission phase. These observations were extended in sequential vertical studies performed in a group of patients. These results suggest that raised CIC detected by the 125I-C1q method may reflect a progressive state in ALL and that quantitation of these immune complexes may provide an adequate biochemical marker for prognosis.


Identification of emulsification proteins released from the cells by inhibiting the synthesis of GPI-anchor or β-1,3-glucan in Candida albicans.
A previous study demonstrated a strong emulsification ability of the culture supernatant obtained by cultivation of Candida albicans in a medium containing a β-1,3-glucan synthesis inhibitor and proposed a novel screening method using emulsification as an indicator for β-1,3-glucan synthesis inhibition (Nerome et al., 2021. Evaluating β-1,3-glucan synthesis inhibition using emulsion formation as an indicator. J Microbiol Methods. 190:106327). The emulsification was presumed to be caused by the proteins released from the cells; however, which proteins have a strong emulsification ability was unclear. Furthermore, as many cell wall proteins are connected to β-1,3-glucan via the carbohydrate moiety of the glycosylphosphatidylinositol (GPI)-anchor, which remains when detached from the cell membrane, emulsification might be detected by inhibiting GPI-anchor synthesis. This study aimed to confirm whether emulsification could be detected by inhibiting GPI-anchor synthesis and identifying emulsification proteins released by inhibiting the synthesis of GPI-anchor or β-1,3-glucan. C. albicans was cultured in a medium containing a GPI-anchor synthesis inhibitor, and the emulsification by the culture supernatant was evaluated. We identified cell wall proteins released from the cells upon inhibition of β-1,3-glucan or GPI-anchor synthesis by mass spectrometry, their recombinant proteins were prepared, and their emulsification efficacy was evaluated. In GPI-anchor synthesis inhibition, a weak emulsification phenomenon was observed compared to the β-1,3-glucan synthesis inhibition. Phr2 protein was released from the cells upon GPI-anchor synthesis inhibition, and recombinant Phr2 showed a strong emulsification activity. Phr2 and Fba1 proteins were released upon β-1,3-glucan synthesis inhibition, and recombinant Fba1 showed a strong emulsification activity. We concluded that the emulsion phenomenon could be used to screen β-1,3-glucan and GPI-anchor synthesis inhibitors. Also, the two kinds of inhibitors could be distinguished by differences in the growth recovery by osmotic support and strength of emulsification. In addition, we identified the proteins involved in emulsification.


Isolation and culture of bovine embryonic stem cells.
Isolation and culture of primary embryonic stem (ES) cell colonies are the first critical step towards establishment of stable ES cell lines. Here we introduce a novel method designated as "Separate and Seed" that contributes remarkably to efficient derivation of bovine primary ES cell colonies from blastocysts. The bovine ES cell colonies can self-renew to passage 10 with the growth factors bFGF and BIO. The bovine ES cells exhibit morphology typical of ES cells and express pluripotent molecular markers including Oct4, Nanog, SSEA1, SSEA4, and alkaline phosphatase (AP). These pluripotent markers may be used for the characterization of authentic bovine ES cell lines. Although continued efforts are required for improving long-term culture of bovine ES cells, this novel "Separate and Seed" method plus the growth factors bFGF and BIO provides an initial effective step that may eventually lead to the derivation of authentic bovine ES cells.


Dietary fibre and fermentability characteristics of root crops and legumes.
The dietary fibre and fermentability characteristics of local root crops and legumes were determined. Total, soluble and insoluble fibre were determined in six root crops (kamote, gabi, potato, tugi, ube, cassava) and ten legumes (mungbean, soyabean, peanut, pole sitao, cowpea, chickpea, green pea, lima bean, kidney bean and pigeon pea) using Association of Official Analytical Chemists methods. The dietary fibre from test foods was isolated and fermented in vitro using human faecal inoculum simulating conditions in the human colon. The SCFA, e.g. acetate, propionate, butyrate, produced after fibre fermentation was measured using HPLC. The dietary fibre content of root crops ranged from 4.6 to 13.5 g/100 g while legumes ranged from 20.9 to 46.9 g/100 g, suggesting that root crops and legumes are good sources of dietary fibre. Significant amounts of SCFA were produced after in vitro fermentation of the fibre isolate of both root crops and legumes. The best sources (as mmol/g fibre isolate) of acetate among the legumes were pole sitao (5.6 (sem 0.5)) and mungbean (5.3 (sem 0.1)) and among the root crops, tugi (2.5 (sem 0.4)) and cassava (2.4 (sem 0.1)); of propionate, kidney bean (7.2 (sem 1.5)) and pigeon pea (3.3 (sem 0.2)) for legumes, and tugi (1.8 (sem 0.2)) for root crops; and of butyrate, peanut (6.0 (sem 0.2)) and cowpea (5.4 (sem 0.2)) for legumes, and tugi (0.8 (sem 0.0)) and cassava (0.8 (sem 0.0)) for root crops. In conclusion, root crops and legumes are good sources of dietary fibre and produced SCFA after fibre fermentation, such as acetate, propionate and butyrate. SCFA production after in vitro fermentation can be estimated using human faecal inoculum and can be used to model the human colon.


Risk factors for dementia in Brazil: Differences by region and race.
Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.


Novel tumor-ablation device for liver tumors utilizing heat energy generated under an alternating magnetic field.
We have developed a novel tumor-ablation device for liver tumors utilizing heat energy induced by magnesium ferrite (MgFe(2)O(4)) particles under an alternating magnetic field (AMF) produced by electric currents. This novel device can repeatedly heat liver tumors at lower temperature than usual heating devices, such as radiofrequency ablation therapy, with slight infliction of pain. This study assesses its heating effect on rat liver tumors as local therapy. The small needle was manufactured from MgFe(2)O(4) particles by sintering at 1100 degrees C. After a MgFe(2)O(4) needle was inserted into liver tumors comprising of dRLh-84 cells, the tumors were heated for 30 min under an AMF. We examined cellular activity by using nicotinamide adenine dinucleotide (NADH) diaphorase staining and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) staining, and evaluated the effect of suppressing tumor growth by sequentially comparing the tumor diameter with that of the control group. The mean temperature of the heated tumors was 60.2 +/- 1.8 degrees C. The tumor cells were constricted, and chromatin of nuclei had shrunk immediately after heating. The heat-injury area that contained the tumors was negative for NADH diaphorase activity. After 3 days, the tumor cells in the heat-injury area became positive for TUNEL staining, which detects cell death. At 7 days, the mean tumor diameters were significantly smaller in the heating group than in the control group (6.15 +/- 0.47 mm vs 16.89 +/- 2.69 mm; P < 0.05). This device, utilizing heat energy induced by ferromagnetic metal under an AMF, appears useful as local thermotherapy for human liver cancer.


Role of dopamine agonists in Parkinson's disease therapy.
Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists.


A clinicopathological study of the effects of topical retinyl propionate cream in skin photoageing.
The clinical and histological effects of retinyl propionate cream (a retinyl ester) on extrinsic skin ageing (photo-ageing) in man were assessed in a double-blind randomized placebo-controlled study of 80 subjects, individual parameters of this being assessed for each treatment site (face, dorsal right forearm and hand, dorsal left forearm and hand) at intervals throughout the study, while skin surface replicas from sites of fine wrinkling around the eye and skin biopsies from the dorsal right forearm were also regularly reviewed throughout. Seventy-five subjects completed an initial 24-week study period, following which 60 elected to continue for a further 24 weeks. Although minimal trends towards improvement occurred, no statistically significant differences between the effects of the retinyl propionate cream and the placebo preparation were apparent for any of the clinical, histological or profilometric parameters of skin photoageing; however, in the very few subjects affected, actinic keratoses in the active group were reduced virtually to zero by week 48.


To love them and to leave them? A review of a Samoan community and health service research project in New Zealand.
The place of Samoan and other Polynesian healing practices and related community projects in New Zealand society has only recently become a subject for study. This paper is an attempt to circumscribe for the people, both Samoan and non-Samoan, with whom I have been working, some of our cross-cultural associations in this field. To do this I have focused on moments in a process which has as many histories and as many futures as there are people participating in it. The interpretation presented here is a chronicle of significant information and events belonging to a 3-year period (1978-1980 inclusive). Behind the choice, to concentrate on describing the process of our dialogue and action rather than the end results--our 'successes' past and present--lie some fundamental questions. Can the growing understanding and on-going communication of people involved in community projects be documented so that this process is appreciated as valuable? This work takes a long commitment by researchers, even if they are members of the community project, and questions of practicality are raised. Is there a method of documentation which is acceptable both to the funding institutions that sponsor community health projects and to the people who are engaged in them? Could the present commonly accepted short-term assessment of end results, which I find objectionable, be right? And researchers evaluating community health projects, should they continue to become involved with the people they are studying for short times and then withdraw--to love them and leave them?


Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer.
Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1-Q3 range (IQR), 0-10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02-1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33-17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.


Platelet-rich plasma improves acute and chronic anal fissure, a randomized control trial.
Anal fissure is one of the most prevalent diagnosis in patients with anorectal symptoms. Depending on the chronicity, treatment choices vary, from topical and conservative management to operative ones. PRP is a blood-derived product with a three to five-fold platelet count and can be used for restorative purposes. The objective of this study is to assess the therapeutic effect of intralesional PRP in acute and chronic anal fissures and comparing it with the classic topical approach. We included 94 patients with acute and chronic anal fissures and divided them into intervention and control groups. Control patients were treated only with topical compounds, and the intervention group received one dose of intralesional autologous PRP plus the same classic treatment. We assessed patients 2 weeks, 1 month, and 6 months later. The mean pain score in the intervention group was significantly lower than control groups in all visits (p-value <0.001). During the follow-ups, the bleeding rate was significantly lower in the intervention group, so in the sixth month, the bleeding was 4% in the intervention group against 32% of the control (p-value <0.001). The healing rate assessed by examination was 96% in the intervention group against 66% in the control in the sixth month (p-value <0.001). Although there may be no significant difference in healing rate between groups in the acute anal fissure, the PRP group is significantly superior in the chronic setting. We concluded that in anal fissure treatment, PRP plus topical products are significantly superior to alone topical treatment.


The problems inherent in promoting research-based practice and strategies by which they might be overcome.
The historical and contemporary impetus for research in nursing is presented in brief. The factors affecting research use in practice are numerous and complicated and include political, financial, ideological and professional spheres. Various strategies that may enhance research use in practice have been suggested and evaluated and these are discussed.


Similarity study of dust emissions from tracked military vehicles with experimental validation.
Accurate prediction of dust emissions from tracked vehicles traveling on unpaved roads is essential for environmental protection and vehicle performance maintenance. However, limited research on dust emissions from tracked vehicles with high precision results from the complex dust emission mechanism and the multitude of influencing factors of tracked vehicles. This paper presents a method for determining the dust emissions from tracked vehicles based on the similarity principle. Specifically, an experimental scheme for the scaling model of T90 tank is designed through the similarity analysis of dust emissions from tracked vehicles, which correlates the mass flow rate of dust emission with seven related variables (soil thickness, dust particle bulk density, dust average particle size, vehicle weight, track width, track landing length, and vehicle speed). The dimensionless empirical equations are obtained by multivariate nonlinear fitting of the experimental results. Furthermore, the applicability of empirical equations is validated experimentally to describe dust emissions from real tracked vehicles. The results show that the similarity principle is a better method to overcome the bottleneck of quantifying dust emissions from tracked vehicles. Meanwhile, the empirical equations derived from the scaling model are also applicable to describe the dust emissions from actual tracked military vehicles.


Loss of proteins from digitonin-permeabilized adrenal chromaffin cells essential for exocytosis.
Cultured chromaffin cells can be permeabilized with digitonin; the cell interior is then accessible to the cytoplasm, and addition of calcium provokes release of catecholamines. Increasing the incubation time between the permeabilization step and calcium-induced stimulation resulted in a progressive inhibition of secretion reaching 60% after 20 min. Cytosoluble proteins which leak from detergent-permeabilized cells were collected, dialyzed, and concentrated. When these proteins were added back to permeabilized cells which were unable to secrete, catecholamine release was fully restored, suggesting that certain proteins necessary for exocytosis had been dialyzed from these cells. One of the released proteins was characterized as calmodulin. However, addition of calmodulin alone was ineffective in maintaining or restoring secretory activity in digitonin-permeabilized cells, excluding calmodulin as the sole factor responsible for the loss of release. Protein kinase C was also identified as one of the leaked proteins. This enzyme is known to be retained in cells in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA). However, under TPA-dependent conditions, there was also a loss of secretory activity. The present paper shows that among the proteins leaked from digitonin-permeabilized cells, there are specific proteins crucial to the exocytotic mechanism.


Visual arts training is linked to flexible attention to local and global levels of visual stimuli.
Observational drawing skill has been shown to be associated with the ability to focus on local visual details. It is unclear whether superior performance in local processing is indicative of the ability to attend to, and flexibly switch between, local and global levels of visual stimuli. It is also unknown whether these attentional enhancements remain specific to observational drawing skill or are a product of a wide range of artistic activities. The current study aimed to address these questions by testing if flexible visual processing predicts artistic group membership and observational drawing skill in a sample of first-year bachelor's degree art students (n=23) and non-art students (n=23). A pattern of local and global visual processing enhancements was found in relation to artistic group membership and drawing skill, with local processing ability found to be specifically related to individual differences in drawing skill. Enhanced global processing and more fluent switching between local and global levels of hierarchical stimuli predicted both drawing skill and artistic group membership, suggesting that these are beneficial attentional mechanisms for art-making in a range of domains. These findings support a top-down attentional model of artistic expertise and shed light on the domain specific and domain-general attentional enhancements induced by proficiency in the visual arts.


[Study of antmicrobial mechanisms of human cervical mucus: isolation and characterization of antibacterial polypeptides].
To isolate and purify antibacterial polypeptides from human cervical mucus. Human cervical mucus was collected from human healthy subjects and acid-soluble extract was obtained by solving the mucus with 5% acetic acid in the presence of protease inhibitors. The antibacterial components were identified by Agar radial diffusion assay and gel overlay technique. For further purification, Preparative acid-urea gel electrophoresis and Reverse Phase HPLC were performed. The N-terminal sequencing and degenerate PCR-directered cDNA cloning were performed. The E. coli-based recombinant product was prepared and its antibacterial property was determined by minimal inhibitory concentration and minimal bactericidal concentration. A purified antibacterial polypeptide was obtained. Agar radial diffusion assay showed that the purified polypeptide had antibacterial activities against E. coli ML-35P and Pseudomanas aeruginosa ATCC 27853. The N-terminal amino acid sequence and its full length of cDNA were identical to High Mobility Group Chromosal protein N2 (HMGN2). The purified recombinant HMGN2 was obtained. Its MIC against E. coli ML-35p and P. aeruginosa ATCC27853 were 10.42 microg/ml +/- 3.13 microg/ml and 27.78 microg/ml +/- 8.33 microg/ml respectively, which were equal to human neutrophil defensins HNP, and the MBC were 20.83 microg/ml +/- 6.25 microg/ml and 55.56 microg/ml +/- 16.67 microg/ml respectively. HMGN2 may be another antibacterial effecter in the defense mechanisms of human cervical mucus.


Joint inflammation alters gene and protein expression and leads to atrophy in the tibialis anterior muscle in rats.
The aim of this study was to evaluate the effect of tibiotarsal joint inflammation in rat tibialis anterior muscle through muscle fiber cross-sectional area (CSA) and gene expression (atrogin-1, muscle ring finger-1 [MuRF1], myogenic differentiation-1 [MyoD], p38 mitogen-activated protein kinase [p38MAPK], nuclear factor kappa B-dependent [NFκB], tumor necrosis factor-alpha [TNF-α]). Wistar rats were randomly divided into three periods (2, 7, and 15 days) and assigned into four groups within each experimental period: control, sham, inflammation, and immobilization. Real-time polymerase chain reaction, Western blot, immunofluorescence, and muscle fiber CSA analyses were performed. At 2 days, the inflammation group increased atrogin-1, MuRF1, and myostatin and reduced MyoD expression. At 7 days, the inflammation group increased atrogin-1, MuRF1, NFκB, p38MAPK, MyoD, myostatin, and TNF-α expression and TNF-α protein and reduced muscle fiber CSA. At 15 days, gene and protein expression in the inflammation group returned to basal levels, and CSA values were similar to those in control and sham groups. The immobilization groups have a similar pattern in all experimental periods, with increased atrogin-1, MuRF1, NFκB, and TNF-α gene expression and reduced muscle fiber CSA. The sham group had increased myostatin and atrogin-1 expression at 2 days and increased MyoD and myostatin expression at 7 days. Joint inflammation stimulated the expression of muscle factors related to atrophy, growth, differentiation, and mass regulation followed by muscle atrophy.


Descending projections to the auditory midbrain: evolutionary considerations.
The mammalian inferior colliculus (IC) is massively innervated by multiple descending projection systems. In addition to a large projection from the auditory cortex (AC) primarily targeting the non-lemniscal portions of the IC, there are less well-characterized projections from non-auditory regions of the cortex, amygdala, posterior thalamus and the brachium of the IC. By comparison, the frog auditory midbrain, known as the torus semicircularis, is a large auditory integration center that also receives descending input, but primarily from the posterior thalamus and without a projection from a putative cortical homolog: the dorsal pallium. Although descending projections have been implicated in many types of behaviors, a unified understanding of their function has not yet emerged. Here, we take a comparative approach to understanding the various top-down modulators of the IC to gain insights into their functions. One key question that we identify is whether thalamotectal projections in mammals and amphibians are homologous and whether they interact with evolutionarily more newly derived projections from the cerebral cortex. We also consider the behavioral significance of these descending pathways, given anurans' ability to navigate complex acoustic landscapes without the benefit of a corticocollicular projection. Finally, we suggest experimental approaches to answer these questions.


To what extent do waste management strategies need adaptation to post-COVID-19?
The world has been grappling with the crisis of the COVID-19 pandemic for more than a year. Various sectors have been affected by COVID-19 and its consequences. The waste management system is one of the sectors affected by such unpredictable pandemics. The experience of COVID-19 proved that adaptability to such pandemics and the post-pandemic era had become a necessity in waste management systems and this requires an accurate understanding of the challenges that have been arising. The accurate information and data from most countries severely affected by the pandemic are not still available to identify the key challenges during and post-COVID-19. The documented evidence from literature has been collected, and the attempt has been made to summarize the rising challenges and the lessons learned. This review covers all raised challenges concerning the various aspects of the waste management system from generation to final disposal (i.e., generation, storage, collection, transportation, processing, and burial of waste). The necessities and opportunities are recognized for increasing flexibility and adaptability in waste management systems. The four basic pillars are enumerated to adapt the waste management system to the COVID-19 pandemic and post-COVID-19 conditions. Striving to support and implement a circular economy is one of its basic strategies.


Importance of Family History in the Era of Exome Analysis: A Report of a Family with Multiple Concurrent Genetic Diseases.
Multiple familial diseases in a single patient often present with overlapping symptomatology that confers difficulty in delineating a clinical diagnosis. Pedigree analysis has been a long-standing practice in the field of medical genetics to discover familial diseases. In recent years, whole exome sequencing (WES) has proven to be a useful tool for aiding physicians in diagnosing and understanding disease etiology. This report shows that pedigree analysis and WES are co-dependent processes in establishing diagnoses in a family with 4 different genetic disorders: Birt-Hogg-Dubé Syndrome, RRM2B-related mitochondrial disease, CDC73-related primary hyperparathyroidism, and familial prostate cancer.


Evaluation of blood flow on the remnant distal bowel during left-sided colectomy.
Adequate blood flow in anastomosis is of paramount importance to prevent anastomotic leakage. However, it is sometimes difficult to predict the viability of the intestine during surgery. During left-sided colectomy, blood flow on the remnant distal bowel is supplied only from the middle and inferior rectal arteries. The blood backflow after the root ligation of the inferior mesenteric artery is often said to be kept up to promontorium levels; however, this premise is actually based on experience, without reliable evidence. Here, we introduce the intraoperative evaluation of blood flow on the remnant distal bowel during left-sided colectomy using an indocyanine green fluorescence technique.


Comparative study between oral and sublingual 600 µg misoprostol for the treatment of incomplete abortion.
To evaluate and compare effectiveness, side effects and patient acceptability between oral and sublingual 600 µg misoprostol for the treatment of incomplete abortion. A randomized controlled trial was conducted. Pregnant women of less than 14 weeks gestation, diagnosed with incomplete abortion, were randomly assigned to receive 600 µg misoprostol orally or sublingually. The patients were evaluated at 48 h after drug administration for complete abortion. A total of 64 women were recruited to the study (32 in the oral group and 32 in the sublingual group). The complete abortion rate was not statistically different between oral and sublingual groups (87.5% versus 84.4%, P > 0.05). There was no statistical difference in side effects and satisfaction rate. Fever/chills were the most common side effects. Both sublingual and oral 600 µg misoprostol are useful for the management of incomplete abortion. Side effects and satisfaction rates are not different. Thus, these methods may be used as alternative treatments of incomplete abortion.


Augmented SIEA flap for microvascular breast reconstruction after prior ligation of bilateral deep inferior epigastric arteries.
The superficial inferior epigastric artery (SIEA) flap is an excellent option for free tissue transfer breast reconstruction. Similar to the free transverse rectus myocutaneous (TRAM) and deep inferior epigastric perforator (DIEP) flaps, the SIEA pedicle supplies the fasciocutaneous tissues of the lower abdomen. The SIEA flap does not involve removal of or potential damage to the rectus muscles. Nonetheless, the vascular pedicle may be a challenge to dissect and variable in its presence and caliber. This article presents a case report and an extended delay technique to augment the SIEA system in a patient with prior bilateral deep inferior epigastric artery ligation.


Surface phenotype of LPS-binding murine lymphocytes.
We have characterized LPS+ murine lymphocytes by determining their surface phenotype using double-labeling immunofluorescence. In the spleen, 40% of cells were LPS+mu+ (B cells), 5% were LPS+Thy 1.2+ (T cells), and 5% were LPS+ cells bearing neither mu nor Thy 1.2 (null cells). Peripheral lymph nodes contained 11% LPS+ B cells and 2% LPS+ T cells, and mesenteric lymph nodes contained 15% LPS+ B cells and 3% LPS+ T cells. In contrast, the 4% LPS+ cells in Peyer's patches were all B cells, and the thymus contained 4% LPS+ T cells. Only the spleen contained LPS+ null cells. Within each lymphoid organ examined, the fraction of total lymphocytes identified as LPS+mu+, LPS+Ia+, or LPS+ delta + was similar, indicating that LPS+ B cells possessed the surface phenotype mu+Ia+ delta +, characteristic of a mature B cell. This conclusion was supported by the absence of LPS+mu+Ia+ delta + cells in newborn spleens. The fraction of mu+Ia+ delta + cells which also binds LPS was highest in spleen and lowest in Peyer's patches. Assuming that cells are, on the average, more mature in the progression from spleen to lymph nodes to Peyer's patches, it would appear that LPS+ cells are a less mature fraction of the mu+Ia+ delta + pool, distinguished by the presence of an LPS binding site or receptor. These data illustrate selective binding of LPS predominantly to mature B cells, but also to small numbers of null cells and T cells. The relationship of this binding to cell activation is discussed by considering the characteristics of cells which can be activated by LPS to clonal growth or differentiation under appropriate conditions.


First-Line Treatment of Driver-Negative Non-Small Cell Lung Cancer.
Immunotherapy-based regimens are an established standard of care for the first-line treatment of driver-negative (EGFR/ALK/ROS WT) advanced non-small cell lung cancer. With multiple immune-based regimens approved in the first-line setting, clinicians are faced in practice with a variety of treatment choices. This article summarizes the most up-to-date trial data on treatments for driver-negative advanced non-small cell lung cancer, including immunotherapy monotherapy, chemoimmunotherapy, and combination immunotherapy, providing a framework for clinicians based on PD-L1 and smoking status. A multibiomarker assay that may best predict immunotherapy response remains an active area of research.


Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31.
Cell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of this study was to explore the potential effects of stem cell-released MVs in proangiogenic therapy. We observed for the first time that MVs were released from adipose-derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the released MVs in vitro. RNA analysis revealed that microRNA was enriched in ASC-released MVs and that the level of microRNA-31 (miR-31) in MVs was notably elevated upon EDM-preconditioning of MV-donor ASCs. Further studies exhibited that miR-31 in MVs contributed to the migration and tube formation of HUVECs, microvessel outgrowth of mouse aortic rings, and vascular formation of mouse Matrigel plugs. Moreover, factor-inhibiting HIF-1, an antiangiogenic gene, was identified as the target of miR-31 in HUVECs. Our findings provide the first evidence that MVs from ASCs, particularly from EDM-preconditioned ASCs, promote angiogenesis and the delivery of miR-31 may contribute the proangiogenic effect. This study provides the evidence that microvesicles (MVs) from adipose-derived stem cells (ASCs), particularly from endothelial differentiation medium (EDM)-preconditioned ASCs, promote angiogenesis. An underlying mechanism of the proangiogenesis may be the delivery of microRNA-31 via MVs from ASCs to vascular endothelial cells in which factor-inhibiting HIF-1 is targeted and suppressed. The study findings reveal the role of MVs in mediating ASC-induced angiogenesis and suggest a potential MV-based angiogenic therapy for ischemic diseases.


EEG changes in intrathecal baclofen overdose: a case report and review of the literature.
To review the clinical and EEG manifestations of intrathecal baclofen overdose. We identified one patient who had received an overdose of intrathecal baclofen. Information about the clinical course was obtained by reviewing the patient's medical record. EEGs were recorded with the use of the standard 10-20 electrode placement system. The patient received 30 mg baclofen intrathecally. Shortly after the injection he developed respiratory insufficiency and quadriparesis and later became comatose. The first EEG obtained 20 h after the injection showed very frequent quasiperiodic generalized epileptiform discharges. The patient gradually improved clinically and a second EEG obtained 24 h later showed only intermittent bursts of generalized slow wave activity. A repeat EEG study 1 week later was normal. The EEG in intrathecal baclofen overdose can show quasiperiodic generalized epileptiform discharges. This does not necessarily indicate the presence of underlying potential epileptogenicity, and treatment with an antiepileptic medication is not necessary.


Seed lost to perineum from hydrogel spacer after brachytherapy for prostate cancer.
We describe a rare case of brachytherapy for prostate cancer in which a seed was lost from the perineum after a hydrogel injection. A 71-year-old Japanese man was diagnosed with localized high-risk prostate cancer. Trimodality therapy with I-125 brachytherapy was selected, and combined androgen blockade therapy was initiated. Brachytherapy and hydrogel injection were performed 7 months after combined androgen blockade initiation; 6 months later, the patient visited our hospital with complaints of redness and bleeding in the perineum. Serous effusion and loss of a seed on the right side of the perineal anus were observed. Pelvic magnetic resonance imaging showed a tunnel like discharge of hydrogel from the dorsal prostate to the perineum. The fistula was incised, the seed was removed, and drainage was performed. Appropriate diagnosis and treatment with careful follow-up are required in patients at high risk of infection after brachytherapy with hydrogel injection.


The spinal root origins and clinical implications of the lower subscapular nerve.
The purpose of this study was to define the spinal root origins of the lower subscapular nerve and the amounts of participating nerve fibers from each spinal root and to discuss the clinical implications. Using a method of separating the nerve fascicles that traces the particular nerve fibers at the intrafascicular level, the spinal root origins of the lower subscapular nerve appeared as two types. The first type comprised 76.9% and was composed of the C5, C6, and C7 roots; the second type comprised 23.1% and was composed of the C6 and C7 roots. The number of nerve fibers was 357.2 +/- 139.7 (mean +/- SD) derived from C5, 1070.4 +/- 390.6 from C6, and 500.0 +/- 285.4 from C7. The nerve fascicles comprising the lower subscapular nerve traveled within the partially common fascicles composed of the axillary nerve. Therefore, injury of the lower subscapular nerve may be accompanied by a lesion of the axillary nerve, which generally consists of C5 and C6 roots composing the posterior cord of the brachial plexus.


Sex differences in professional help seeking among adult black Americans.
This paper provides baseline data on sex differences in the use of professional help for serious personal problems in a nationally representative sample of adult black Americans. Bivariate analyses revealed that women had higher levels of psychological distress and were significantly more likely to seek professional help than were men. They were also more likely to utilize physicians and social service agencies. The relationship of gender to these help resources remained significant even when the effects of problem severity and differential problem definition were taken into account. Controlling for income, however, eliminated the sex difference for social services use but not for physician use.


Extensive retroviral diversity in shark.
Retroviruses infect a wide range of vertebrates. However, little is known about the diversity of retroviruses in basal vertebrates. Endogenous retrovirus (ERV) provides a valuable resource to study the ecology and evolution of retrovirus. I performed a genome-scale screening for ERVs in the elephant shark (Callorhinchus milii) and identified three complete or nearly complete ERVs and many short ERV fragments. I designate these retroviral elements "C. milli ERVs" (CmiERVs). Phylogenetic analysis shows that the CmiERVs form three distinct lineages. The genome invasions by these retroviruses are estimated to take place more than 50 million years ago. My results reveal the extensive retroviral diversity in the elephant shark. Diverse retroviruses appear to have been associated with cartilaginous fishes for millions of years. These findings have important implications in understanding the diversity and evolution of retroviruses.


Rubidium, salami and depression. You cannot have everything in life.
Depression may induce malnutrition, but, as a paradoxical hypothesis, malnutrition may induce depression. This relationship, of course, depends on how we define malnutrition. Rubidium is a trace element strongly linked with depression, and is deficient in uremia sufferers. However, in uremic patients, rubidium deficiency is more evident during predialysis, as it is at least partially corrected during dialysis and after transplantation. It seems that diet restrictions might be the main cause of rubidium deficiency, as it is mainly found in red meat. If rubidium is found in salami, then the occasional slice could be more beneficial for people suffering from depression than taking a lot of medication.


Chronic postinfarction pseudo-pseudoaneurysm diagnosed by cardiac MRI.
Left ventricular pseudo-pseudoaneurysm is an extremely rare complication of myocardial infarction. In this condition the postinfarction rupture of the myocardium is not transmural, but remains circumscribed within the ventricular muscle itself as a cavity joining to the left ventricle through a narrow neck. The differentiation between postinfarction pseudoaneurysms and pseudo-pseudoaneurysms may be very difficult using conventional imaging techniques, such as transthoracic, or transesophageal echocardiography and left ventricular angiography. Cardiac MRI (CMR), however, is capable of distinguishing among anatomical structures such as pericardium, thrombus, and myocardium. In our report a chronic postinfarction pseudo-pseudoaneurysm is described by CMR in a patient with an old myocardial infarction.