Occurrence and removal efficiencies of benzotriazoles and benzothiazoles in a wastewater treatment plant in Greece.
Despite the widespread use of benzotriazoles and benzothiazoles and the occurrence of these compounds in wastewater treatment plants (WWTPs), no earlier study has comprehensively examined their fate in WWTPs. In this study, an integrated liquid chromatography-tandem mass spectrometry (LC-ESI(+)MS/MS) method was developed and validated for simultaneous determination of four benzotriazoles and four benzothiazoles in dissolved and particulate phases of wastewater (raw and treated), and in dewatered sewage sludge. The target benzotriazoles (BTRs) were 1H-benzotriazole, 1-hydroxy-benzotriazole, tolyltriazole, and xylyltriazole (or 5,6-dimethyl-1H-benzotriazole), and the target benzothiazoles (BTHs) were benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, and 2-amino-benzothiazole. The limits of detection ranged from 0.08 (2-methylthio-benzothiazole) to 17 ng/L (benzothiazole) for dissolved phase samples, and from 0.04 (2-methylthio-benzothiazole) to 13 ng/g dry weight (dw) (benzothiazole) for particular matter and sludge samples. The method was applied in the analysis of wastewater and sludge samples from the WWTP in Athens, Greece. All target chemicals were detected in wastewater samples, and in some cases the concentrations were significant, on the order of a few μg/L. In sludge samples, benzothiazole and tolyltriazole were present at the highest concentrations (174 and 116 ng/g dw, respectively). For benzotriazole and tolyltriazole, the removal efficiency was below 68%, and for benzothiazoles, the removal efficiency was greater than 64% in the activated sludge treatment process. Both BTRs and BTHs showed low solid-liquid distribution coefficients.


Quadrature and the development of orientation selective cortical cells by Hebb rules.
We describe a new theoretical scenario for the development of orientation selective cells in a self-organizing feedforward network with modifiable synapses. A suitable choice of Hebb rule leads to a system that develops symmetric and antisymmetric response fields (quadrature pairs) at the same time as directional selectivity occurs using inhibition between neighboring cells. Quadrature phase relationships between the response properties of adjacent cortical cells is suggestive of several highly efficient information processing strategies.


Anxiety treatment improves physical functioning with oblique scoring of the SF-12 short form health survey.
No studies have found a positive effect of anxiety treatment on physical functioning, but recent investigations of the 12-item Short Form Health Questionnaire (SF-12), which is frequently used to assess physical functioning, have suggested that orthogonal scoring of the summary measure may distort representations of physical health. The current study reanalyzes whether anxiety treatment improves physical functioning using oblique scoring in the Coordinated Anxiety Learning and Management (CALM) randomized clinical trial for the treatment of anxiety disorders. Replication was tested in reanalysis of data from the earlier Collaborative Care for Anxiety and Panic (CCAP) randomized clinical trial for the treatment of panic disorder. The CALM study included 1004 primary care patients with panic, social anxiety, generalized anxiety or posttraumatic stress disorders. Patients received usual care (UC) or an evidence-based intervention (cognitive behavioral therapy, psychotropic medication or both; ITV). Physical functioning (SF-12v2) was assessed at baseline and at 6, 12 and 18 months. Oblique and orthogonal scoring methods for the physical functioning aggregate measure from SF-12 scale items were compared. In CALM, physical functioning improved to a greater degree in ITV than UC for oblique but not orthogonal scoring. Findings were replicated in the CCAP data. Evidence-based treatment for anxiety disorders in primary care improves physical functioning when measured using oblique scoring of the SF-12. Due to this scoring issue, effects of mental health treatment on physical functioning may have been understated.


Insulin-induced glycerolipid mediators and the stimulation of glucose transport in BC3H-1 myocytes.
We have previously demonstrated that insulin stimulates glycerolipid synthesis and phospholipid hydrolysis in BC3H-1 myocytes, resulting in the generation of membrane diacylglycerol, a known cellular mediator. This led us to the original proposal that diacylglycerol may contribute to the mediation of insulin action, especially stimulation of glucose transport. The fact that agents such as phenylephrine and phorbol esters, which increase or act as membrane diacylglycerols, are fully active in stimulating glucose transport in this tissue lent further support to this proposal. In this paper, we demonstrate that the diacylglycerol analogues PMA (4 beta-phorbol 12-myristate 13-acetate) and mezerein (both possessing 12 beta- and 13 alpha-O-linked substituents as well as a 4 beta-hydroxyl group) each increase the Vmax of the glucose transporter as does insulin. Diacylglycerol generated by the addition of phospholipase C also stimulates glucose uptake to a maximum which is equal and nonadditive to that of insulin, while addition of the narrowly active phosphatidylinositol-specific phospholipase C which generates the putative phosphoinositol-glycan mediator of Saltiel et al. (Saltiel, A., Fox, J., She Lin, P., and Cutrecasas, P. (1986) Science 233, 967-972) stimulates pyruvate dehydrogenase in these cells without any effect on glucose uptake. Pretreatment of the myocytes with PMA resulted in desensitization of subsequent glucose uptake to stimulation by phenylephrine, but had no effect on stimulation of glucose uptake by phospholipase C or by insulin, indicating that PMA pretreatment primarily desensitizes agonist-induced polyphosphoinositide hydrolysis which, as we have previously shown, is not involved in the insulin-induced generation of diacylglycerol. This was confirmed by the absence of intracellular Ca2+ mobilization during insulin administration, as measured by the sensitive fluorescent probe fura-2 in attached monolayer BC3H-1 myocytes. Furthermore, we have shown that insulin-generated diacylglycerol satisfies several criteria for a mediator of insulin action, including the demonstration that insulin-stimulated endogenous diacylglycerol generation is antecedent to glucose transport and has an identical insulin dose-response curve and moreover that the magnitude and time course of subsequent stimulation of glucose transport is reproduced by the addition of the simple exogenous diacylglyerol, dioctanoylglycerol, in the complete absence of the hormone. These results establish a central role for insulin-induced glycerolipid metabolism in mediating insulin-stimulated glucose transport in BC3H-1 myocytes.


The relationship between motor and secretory behaviors in classical appetitive conditioning.
Three hungry dogs received pairings of food with an accessible, illuminated panel. This resulted in the dogs' approaching the lighted panel and salivating. Despite the similarity of these conditioning procedures to those used in a large body of research primarily with avians, however, the dogs did not physically contact the lighted stimulus panel. These results bear on several issues concerning the form and direction of classically conditioned behaviors.


Comprehensive adsorption and spectroscopic studies on the interaction of magnetic biochar from black wattle sawdust with beta-blocker metoprolol.
The rise of contaminants of emerging concern in water-resources due to human activities has driven research toward wastewater treatment, specifically adsorption. The utilization of woody biomass for biochar production in adsorption has shown promise due to its high availability. This study shows the preparation of magnetic biochars (MB) from waste black wattle sawdust, utilizing ZnCl2 and NiCl2 (proportions: 1:0.5:0.5 = MB-0.5 and 1:1:1 = MB-1) as activating and magnetic agents. Synthesized via microwave-assisted-pyrolysis, MB boasts a high surface area (up to 765 m2.g-1) and functional groups, enhancing metoprolol medicine adsorption. Nonlinear kinetic and isothermal models were tested; the Avrami fractional-order kinetic model and Liu's isothermal model provided the best fits for experimental data. Thermodynamics and spectroscopic studies revealed spontaneous and exothermic adsorption processes, with physisorption magnitude and dominance of hydrogen-bond and π-π-interactions. MB can be easily extracted from an aqueous medium using magnetic fields, while adsorption capacity could be regenerated through green solvent elution.


Hepatocellular carcinoma in noncirrhotic patients. A laparoscopic study of 92 cases in Taiwan.
Clinical and laboratory findings of 92 cases of pathologically verified noncirrhotic primary hepatocellular carcinoma (HCC) were analyzed and compared with that of 174 cases of cirrhotic HCC during the same period. Ninety-two cases of noncirrhotic HCC constitute one third of all the cases of HCC. They comprised 74 men (80.4%) and 18 women (19.6%) with a male:female ratio of 4.1. The mean age was 52.0 +/- 14.5 years. Among them, 17.4% had a history of hepatitis; 65.2% were HBsAg positive. Compared with cirrhotic HCC, patients with noncirrhotic HCC had less frequent past history of hepatitis, lower positive rate for HBsAg, higher albumin/globulin ratio, and lower frequency in the elevation of serum alpha-fetoprotein. The results might imply that noncirrhotic and cirrhotic HCC have different pathogenetic backgrounds.


Preoperative Ultrasound Scoring of Endometriosis by AAGL 2021 Endometriosis Classification Is Concordant with Laparoscopic Surgical Findings and Distinguishes Early from Advanced Stages.
To compare the accuracy of preoperative ultrasound (US) in predicting the laparoscopically defined 2021 American Association of Gynecologic Laparoscopists (AAGL) Endometriosis Staging. Retrospective multicenter study of patients treated at 3 specialized endometriosis centers. Three specialized endometriosis surgical centers in São Paulo (Brazil), Barcelona (Spain), and Avellino (Italy) participated. A total of 878 patients aged 15 to 45 years with no history of pelvic malignancy underwent laparoscopic (LPS) treatment for suspected endometriosis. Retrospective review of preoperative transvaginal and transabdominal US (index test) assessed for endometriosis at all sites used in the 2021 AAGL Endometriosis Classification and classified patients into AAGL-US stages 1 to 4. Results were compared with reference-standard LPS (AAGL-LPS) staging. The AAGL-US and AAGL-LPS stage were concordant in 586 cases (66.7%) (weighted kappa [WK] 0.759; intraclass correlation = 0.906), with the highest agreement observed in patients with no endometriosis (n = 70, 75.3% concordance), AAGL-LPS stage 1 (104, 50.7%) and stage 4 disease (358, 88.2%). Endometriosis was most accurately diagnosed in the rectum/sigmoid colon (WK 0.862), bladder (WK 0.911), and ovaries (WK 0.835/0.795 for right/left, respectively) and least accurately diagnosed at superficial peritoneal (WK 0.442), tubal (WK 0.391/0.363 for right/left, respectively), and retrocervical/uterosacral ligament (WK 0.656) sites. Sonographic estimation of the 2021 AAGL Endometriosis Staging is greatest in AAGL-LPS stages 1 and 4 and among patients with no endometriosis. US best identifies endometriosis of the ovaries, bladder, and bowel but is more limited for the tubes and superficial peritoneum.


[Duplex scanning of the changes in the vertebral arteries in patients with ischemic stroke in the vertebro-basilar basin].
With duplex scanning of neck vessels in 120 patients with acute ischemic stroke in the vertebrobasilar basin revealed changes in the vertebral artery in (68.3%) of patients, which cause difficulty in blood flow in the vessels of vertebro-basilar basin. Among them were seen often atherosclerotic stenoses (53.3%), deformation (11.7%) and abnormal discharge of vertebral arteries (3.3%).


A comparative clinical assessment of a hollow-fibre membrane oxygenator (Capiox II) and a bubble oxygenator (Harvey 1500).
Personal experience is reported on the use of a membrane oxygenator, the Capiox II, which is clinically compared with a bubble oxygenator for medium-term perfusion. The characteristics considered were the efficiency of the heat exchanger, the oxygenating capacity, traumatic effects on the blood and the direct effect on the renal and cardiopulmonary systems. The Capiox II demonstrated a better oxygenating capacity, less platelet damage, a smaller variation in the free plasma haemoglobin, a significant difference in postoperative bleeding and blood transfusion requirements, but showed no variation in renal and cardiopulmonary function. The authors suggest that the Capiox II is to be preferred for extra-corporeal circulation of medium duration, for which it combines the advantages of both bubble and membrane oxygenators, while being less complex and costly than previously marketed membrane devices.


Well-being and cultural identity for Māori: Knowledge of iwi (tribal) affiliations does not strongly relate to health and social service outcomes.
Research indicates that experiences in health and social services vary depending on identity. For Indigenous groups, identity and affiliation is complex. This paper explores ethnicity and knowledge of tribal (iwi) affiliations for Māori (the Indigenous peoples of Aotearoa New Zealand), and links this to health and social service outcomes in administrative data, the national Census, and Māori social survey data. While many initiatives have sought to connect Māori to iwi - where such knowledge has been severed by colonization - we find surprisingly few differences in data between those who named tribal affiliations and those who did not, across sole- and mixed-Māori ethnicity groups. Those who did not name an iwi were less likely to live in overcrowded homes, but were less likely to own that home, and more likely to be a smoker. Unsurprisingly, those who did not name tribal affiliations were less likely to find Māori culture as important, although many still did. These groups also had slightly less contact with social networks and support, plus felt lonelier. The results also point to sole-ethnic identification as Māori as a key marker of experiences of inequity and suggest that connections to tribal affiliations are more complicated than a binary of "connected" or "disconnected". However, in some indicator areas, affiliation differences should be followed up with future work. We argue these results give further weight to the need for good quality data and indicators designed with Māori populations in mind to measure and monitor inequity.


Association of Long COVID with housing insecurity in the United States, 2022-2023.
To assess the association of Long COVID with housing insecurity in the United States. To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don't report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative cross-sectional survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-today life were associated with a higher prevalence of housing insecurity. During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity. Compared with COVID-19 survivors who don't experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-today life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.


Cloning of murine early quiescence-1 gene: the murine counterpart of dermatopontin gene can induce and be induced by cell quiescence.
Using the method of differential display, we identified a murine gene (GenBank accession number ) specifically expressed in quiescent cells, that is, BALB/c 3T3 cells rendered quiescent by serum deprivation or by contact inhibition. The cloned promoter was 1367 bp in length (accession number ). This gene was called early quiescence-1 (EQ-1) gene because its induction could be detected within 3 h following serum deprivation. EQ-1 is markedly expressed in the heart and lung. The full-length EQ-1 cDNA, cloned from a mouse lung cDNA library, is 1673 bp in length and consists of 26 bp 5' untranslated region, 603 bp coding region, and 1044 bp 3' untranslated region, the latter of which harbors two polyadenylation signals. Because the deduced amino acid residues are of 92% homology to human dermatopontin, EQ-1 represents the murine counterpart of the human dermatopontin. The stably transfected cell line harboring EQ-1 driven by an inducible promoter showed approximately 50% inhibition on cell proliferation after being treated with an inducer for 5 days. These results suggest that the cell quiescence-induced EQ-1 gene can induce cell quiescence, implicating a self-driven mechanism of antiproliferation.


Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats.
Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SD or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats.


Common Risk Variants in AHI1 Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.
Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at HLA-DQ/DR and have identified several non-HLA loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry. We conducted a GWAS in a cohort of Sri Lankan individuals comprising 420 pediatric patients with SSNS and 2339 genetic ancestry matched controls obtained from the UK Biobank. We then performed a transethnic meta-analysis with a previously reported European cohort of 422 pediatric patients and 5642 controls. Our GWAS confirmed the previously reported association of SSNS with HLA-DR/DQ (rs9271602, P = 1.12 × 10-27, odds ratio [OR] = 2.75). Transethnic meta-analysis replicated these findings and identified a novel association at AHI1 (rs2746432, P = 2.79 × 10-8, OR = 1.37), which was also replicated in an independent South Asian cohort. AHI1 is implicated in ciliary protein transport and immune dysregulation, with rare variation in this gene contributing to Joubert syndrome type 3. Common variation in AHI1 confers risk of the development of SSNS in both Sri Lankan and European populations. The association with common variation in AHI1 further supports the role of immune dysregulation in the pathogenesis of SSNS and demonstrates that variation across the allele frequency spectrum in a gene can contribute to disparate monogenic and polygenic diseases.


Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy.
Brain derived neurotrophic factor (BDNF) elevation in newborn sera predicts intellectual/social developmental abnormalities. Other autoantibodies (AAs) to endothelial cells (ECs) and myelin basic protein (MBP) are also elevated in some children. We tested relationships between BDNF, BDNF AAs, and other AAs in children with these disorders. BDNF levels and IgG/IgM autoantibodies to BDNF, ECs, MBP, and histones were measured in children with autism, childhood disintegrative disorder (CDD), pervasive developmental delay-not otherwise specified (PDD-nos), acquired epilepsy, Landau-Kleffner syndrome (LKS); healthy children (HC), and children with non-neurological illnesses (NNI). Mean BDNF levels were elevated in children with autism and CDD, (p < or = 0.0002) compared to HC or NNI. Mean IgG and IgM BDNF AAs were elevated in children with autism, CDD and epilepsy (p < or = 0.0005) compared to HC but not to NNI. Mean IgM AA EC titers detected by immunocytochemistry were higher in autism, PDD-NOS, epilepsy, and LKS (p < or = 0.005) compared to HC and NNI. While mean ELISA IgG EC AAs were higher in autism and PPD-NOS (p < 0.005) compared to HC but not NNI, ELISA IgM EC AAs were higher in children with autism, CDD, PDD-NOS, and epilepsy compared to both HC and NNI (p < 0.0005). Mean anti-MBP IgG and IgM titers were higher in all study groups (p < 0.005) except for LKS compared to both HC and NNI. Children with developmental disorders and epilepsy have higher AAs to several neural antigens compared to controls. The presence of both BDNF AAs and elevated BDNF levels in some children with autism and CDD suggests a previously unrecognized interaction between the immune system and BDNF.


Identification and function of miRNA-mRNA interaction pairs during lateral root development of hemi-parasitic Santalum album L. seedlings.
Sandalwood (Santalum album L.) is a hemi-parasitic tree species famous for its santalol and santalene, which are extracted from its heartwood and roots. The ability to understand root functionality within its branched root system would benefit the regulation of sandalwood growth and enhance the commercial value of sandalwood. Phenotypic and anatomical evidence in this study indicated that seed germination stage 4 (SG4) seemed pivotal for lateral root (LR) morphogenesis. Small RNA (sRNA) high-throughput sequencing of root tissues at three sub-stages of SG4 (lateral root primordia initiation (LRPI), lateral root primordia development (LRPD), and lateral root primordia emergence (LRPE)) was performed to identify microRNAs (miRNAs) associated with LR development. A total of 135 miRNAs, including 70 differentially expressed miRNAs (DEMs), were screened. Ten DEMs were selected to investigate transcript abundance in different organs or developmental stages. Among 100 negative DEM-mRNA interaction pairs, four targets (Sa-miR166m_2, 408d, 858a, and novel_Sa-miR8) were selected for studying cleavage sites by 5' RLM-RACE validation. The expression mode of the four miRNA-mRNA pairs was investigated after indole-3-acetic acid (IAA) treatment. IAA enhanced the abundance of homeobox-leucine-zipper protein 32 (HOX32), laccase 12 (LAC12), myeloblastosis86 (MYB86), and pectin methylesterase inhibitor6 (PMEI6) target transcripts by reducing the expression of Sa-miR166m_2, 408d, 858a, and novel_Sa-miR8 in the first 10 min. A schematic model of miRNA-regulated LR development is proposed for this hemi-parasitic species. This novel genetic information for improving sandalwood root growth and development may allow for the cultivation of fast-growing and high-yielding plantations.


Shifting the paradigm of coral-reef 'health' assessment.
Coral reefs are in crisis. Globally, our reefs are degrading at an accelerating rate and present methodologies for coral-reef 'health' assessment, although providing important information in describing these global declines, have been unable to halt these declines. These assessments are usually employed with no clear purpose and using uncorrelated methods resulting in a failure to prevent or mitigate coral reef deterioration. If we are to ever successfully intervene, we must move beyond the current paradigm, where assessments and intervention decisions are based primarily on descriptive science and embrace a paradigm that promotes both descriptive and mechanistic science to recognize a problem, and recognize it before it becomes a crisis. The primary methodology in this alternative paradigm is analogous to the clinical and diagnostic methodologies of evidence-based medicine. Adopting this new paradigm can provide the evidence to target management actions on those stressors currently impacting reef ecosystems as well as providing a means for proactive management actions to avert irreversible habitat decline.


Urinary GH and IGF-I excretion in nine year-old children: relation to sex, current size and size at birth.
To study the relationship of 24-hour urinary growth hormone (GH) and IGF-I excretion in childhood to sex and body size. To test the hypothesis that small size at birth followed by postnatal catch-up growth is associated with elevated IGF-I production. Follow-up study of a cohort of 183 healthy children born in Salisbury, UK. Weight and height, 24-h urinary growth hormone (uGH) and IGF-I (uIGF-I) excretion, and systolic and diastolic blood pressures. At 9 years of age, 24-h uIGF-I excretion, but not uGH excretion, was strongly related to current weight (P < 0.001) and height (P < 0. 001). Urinary GH and IGF-I excretion were positively correlated (r = 0.15, P = 0.05). Boys excreted more uIGF-I per unit uGH than girls (uIGF-I/uGH molar ratio 32.1 compared to 21.0; P for difference = 0. 002). There were no significant relationships of uGH, uIGF-I or uIGF-I/uGH molar ratio with birthweight, birthlength or head circumference at birth, nor with blood pressure at 9 years. 'Catch-up' growth, indicated by an increase in height SD scores between birth and 9 years, was associated with higher IGF-I excretion (P = 0.01) and occurred in children with taller parents (P < 0.001). Boys appear to be more sensitive to GH than girls, generating more uIGF-I in relation to uGH. Urinary IGF-I excretion at 9 years is related to both absolute height and to the degree of catch-up in height from birth. Our results suggest that IGF-I production is strongly influenced by genetic factors, but also by either the degree to which intrauterine growth falls short of genetic growth potential, or the process of postnatal catch-up growth that follows.


Effects of two guideline implementation strategies on patient outcomes in primary care: a cluster randomized controlled trial.
Cluster randomized controlled trial. To improve quality of care for patients with low back pain (LBP) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practices. We studied effects on functional capacity (main outcome), days in pain, physical activity, quality of life, or days of sick leave (secondary outcomes) compared with no intervention. International research has lead to the development of the German LBP guideline for general practitioners. However, there is still doubt about the most effective implementation strategy. Although effects on process of care have been observed frequently, changes in patient outcomes are rarely seen. We recruited 1378 patients with LBP in 118 general practices, which were randomized to 1 of 3 study arms: a multifaceted guideline implementation (GI), GI plus training of practice nurses in motivational counseling (MC), and the postal dissemination of the guideline (controls, C). Data were collected (questionnaires and patient interviews) at baseline and after 6 and 12 months. Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders. After 6 months, functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls (95% CI = 0.320-6.979, P = 0.032) and 2.652 between the GI group and controls (95% CI = -0.704 to 6.007, P = 0.120). Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 (GI) to 17 days (MC) after 6 months (12 and 9 days after 12 months) compared with controls. Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination. Results are more distinct when practice nurses are trained in motivational counseling.


Nanobody@Biomimetic mineralized MOF as a sensing immunoprobe in detection of aflatoxin B1.
Nanobody(Nb) is too small to carry more signal reporters, which often leads to low sensitivity in immunoassay. Herein, we proposed a novel immunoprobe integration of Nb and biomimetic mineralized metal-organic frameworks(MOF), in which plenty of succinylated horseradish peroxidase(sHRP) were encapsulated within a single MOF and the Nb was assembled on the biomimetic mineralized MOF. It overcomes the dilemma that the Nb is difficult to carry more signal reporters. Meanwhile, the mineralized MOF can protect the sHRP from denaturation and facilitate the transport of substrates to the active sites of sHRP. Electrosensing of aflatoxin B1(AFB1) was realized with a competitive format in which the target AFB1 and immobilized artificial antigen were competing for binding with the immunoprobe. Additionally, the detection signal was enlarged by the catalysis of this immunoprobe to 4-chloro-1-naphthol for producing precipitations, which blocked the channels of the immunoprobe and the redox probes of Fe(CN)63-/4- was difficult to reach the electrode surface through the channels. Hence, the as-prepared immunosensor exhibited good voltammetry responses towards the determined AFB1 in a linear range of 50.0 fg/mL - 20.0 ng/mL with a detection limit of 20.0 fg/mL. The specificity, stability, and reproducibility of this immunosensor were satisfactory. This work may provide an alternative idea for the application of Nb in immunoassay, and the idea may also be applicable to other bio-recognition elements for immunoassay.


Carotid body oxygen sensing and adaptation to hypoxia.
The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O2-sensitive K(+) channels which leads to cell depolarization and the opening of Ca(2+) channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo- or hyper-activation may also contribute to the pathogenesis of several prevalent human diseases.


What Is a "Good" Treatment Decision? Decisional Control, Knowledge, Treatment Decision Making, and Quality of Life in Men with Clinically Localized Prostate Cancer.
We explored whether active patient involvement in decision making and greater patient knowledge are associated with better treatment decision-making experiences and better quality of life (QOL) among men with clinically localized prostate cancer. Localized prostate cancer treatment decision making is an advantageous model for studying patient treatment decision-making dynamics because there are multiple treatment options and a lack of empirical evidence to recommend one over the other; consequently, it is recommended that patients be fully involved in making the decision. Men with newly diagnosed clinically localized prostate cancer (N = 1529) completed measures of decisional control, prostate cancer knowledge, and decision-making experiences (decisional conflict and decision-making satisfaction and difficulty) shortly after they made their treatment decision. Prostate cancer-specific QOL was assessed at 6 months after treatment. More active involvement in decision making and greater knowledge were associated with lower decisional conflict and higher decision-making satisfaction but greater decision-making difficulty. An interaction between decisional control and knowledge revealed that greater knowledge was only associated with greater difficulty for men actively involved in making the decision (67% of sample). Greater knowledge, but not decisional control, predicted better QOL 6 months after treatment. Although men who are actively involved in decision making and more knowledgeable may make more informed decisions, they could benefit from decisional support (e.g., decision-making aids, emotional support from providers, strategies for reducing emotional distress) to make the process easier. Men who were more knowledgeable about prostate cancer and treatment side effects at the time that they made their treatment decision may have appraised their QOL as higher because they had realistic expectations about side effects.


[The research on 3-D maxillofacial soft tissue reconstruction by spiral CT].
To evaluate the role of spiral CT in 3-D reconstruction of maxillofacial soft tissues. Spiral CT was given to a patient who had his right ear absent. The data was recorded in DICOM format. Digital image was reconstructed on GE advantage workstation in SSD way. Spiral CT can quickly and precisely scan and reconstruct the whole head, the reconstructed images of facial soft tissues and apparatus were very clear, but the site of pupil can not display. Except for the pupils, spiral CT is a useful way for maxillo-facial soft tissue reconstruction. It can be widely used in hospitals.


The prognostic value of intraoperative HRV during anesthesia in patients presenting for non-cardiac surgery.
To examine the prognostic value of HRV measurements during anesthesia for postoperative clinical outcomes prediction using machine learning models. VitalDB, a comprehensive database of 6388 surgical patients admitted to Seoul National University Hospital. Cases with ECG lead II recording duration of less than one hour were excluded. Cases with more than 20% of missing HRV measurements were also excluded. A total of 5641 cases were eligible for the analyses. Six machine learning models including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Trees (GBT), Extreme Gradient Boosting (XGB), and an ensemble of the five baseline models were developed to predict postoperative clinical outcomes. The prediction models were trained using only clinical information, and using both clinical information and HRV features, respectively. Feature importance based on the SHAP method was used to assess the contribution of the HRV measurements to the outcome predictions. Subgroup analysis was also performed to evaluate the risk association between postoperative ICU stay and various HRV measurements such as heart rate, low-frequency power (LFP), and short-term fluctuation DFA [Formula: see text]. The final cohort included 5641 unique cases, among whom 4678 (83.0%) cases had ages over 40, 2877 (51.0%) were male, 1073 (19.0%) stayed in ICU after surgery, 52 (0.9%) suffered in-hospital death, and 3167(56.1%) had a total length of hospital stay longer than 7 days. In the final test set, the highest AUROC performance with only clinical information was 0.79 for postoperative ICU stay, 0.58 for in-hospital mortality, and 0.76 for the total length of hospital stay prediction. Importantly, using both clinical information and HRV features, the AUROC performance was 0.83, 0.70, and 0.76 for the three clinical outcome predictions, respectively. Subgroup analysis found that patients with an average heart rate higher than 70, low-frequency power (LFP) < 33, and short-term fluctuation DFA [Formula: see text] < 0.95 during anesthesia, had a significantly higher risk of entering the ICU after surgery. This study suggested that HRV measurements during anesthesia are feasible and effective for predicting postoperative clinical outcomes.


Anticryptococcal type D antibodies raised in rabbits.
Antibodies to Cryptococcus neoformans Type D have been raised in rabbits. The partially purified antibody pool was fractionated by affinity-chromatography, and it was shown that antibodies to the capsular polysaccharide of Type D were present in the pool. Neither methyl alpha-D-mannopyranoside, nor D-mannose were inhibitors of the binding of Type D polysaccharide to the antibody-pool. Thus it appears that the serum contains antibody populations which are specific for terminal side-chain carbohydrate moieties of the immunizing antigen.


New methylene blue-mediated photodynamic inactivation of multidrug-resistant Fonsecaea nubica infected chromoblastomycosis in vitro.
Chromoblastomycosis is a fungal disease presented with local warty papule, plaque, and verrucous nodules. In addition, the incidence and drug resistance of chromoblastomycosis are increasing each year worldwide. Photodynamic therapy is a promising method to treat mycoses. The purpose of this study was to evaluate the effect of new methylene blue (NMB)-induced PDT on multidrug-resistant chromoblastomycosis in vitro. We isolated one wild-type strain pathogen from one clinical patient diagnosed with chromoblastomycosis for over 27 years. The pathogen was identified by histopathology, the morphology of fungal culture, and genetic testing. Drug susceptibility testing was performed on the isolate. It was cultured with logarithmic growth phase spore in vitro and incubated with different concentrations of NMB for 30 min, and received illumination by red light-emitted diode with different light doses. After photodynamic treatment, the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were conducted. The pathogen was Fonsecaea nubica, and it was resistant to itraconazole, terbinafine, amphotericin B, voriconazole andcaspofungin. At the same NMB concentration, the sterilization efficiency of NMB-photodynamic therapy (PDT) on F. nubica increased with increasing light intensity; F. nubica was completely killed at 25 µmol/L NMB with a light dose of 40 J/cm2 or 50 µmol/L NMB and light doses of ≥ 30 J/cm2. SEM and TEM observed ultrastructural changes after PDT. NMB-PDT inactivates the survival of multidrug-resistant F. nubica in vitro; it therefore has the potential to become an alternative or adjuvant treatment for refractory chromoblastomycosis.


On the modified Tabor parameter for the JKR-DMT transition in the presence of a liquid meniscus.
The JKR, DMT, Maugis models and Tabor parameter for contact under normal loading have been developed based mainly on solid-solid (van der Waals) interactions. In this case, the characteristic length scale for the adhesive forces in the Tabor parameter is the equilibrium interatomic spacing. However, for contact in humid environments, where a liquid meniscus may be present, capillary forces with a longer force range related to the Kelvin radius dominate. Fogden and White [J. Colloid Interface Sci. 138 (1990) 414] introduced a parameter that includes the Kelvin radius for the JKR-DMT transition. This topic was also addressed by Maugis and Gauthier-Manuel [J. Adhes. Sci. Technol. 8 (1994) 1311] who included capillary effects within the frame work that Maugis had previously established. The parameters introduced by Fogden and White and Maugis and Gauthier-Manuel can be viewed as a modified Tabor parameter for the JKR-DMT transition. In the present work, the Kelvin equation linking the Kelvin radius and the relative humidity was explicitly included in the modified Tabor parameter. This provided a quantitative description of the JKR-DMT transition in terms of the relative humidity. This parameter was examined via load and contact radius measurements, where the latter were obtained from Bowden and Tabor's assumption that the friction force f=tauA. The friction experiments were conducted at two different humidity levels using a newly-developed mesoscale friction tester (MFT), which provides a very wide range of contact radii. The modified Tabor parameter was used to reexamine data from pull-off experiments in water and cyclohexane vapor environments [L.R. Fisher, J.N. Israelachvili, Colloids Surf. 3 (1981) 303 and H.K. Christenson, J. Colloid Interface Sci. 121 (1988) 170]. Finally, guidelines are presented for the appropriate choice of contact mechanics models to be used in interpreting data from SFA and AFM experiments in humid environments.


Characterization of GATA/GACA-related sequences on proximal chromosome 17 of the mouse.
Autosomal loci have long been thought to have a role in sex determination of mice. We studied the localization of GATA/GACA repeats on chromosome 17 in regard to the possibility of their involvement in sex determination. We performed in situ hybridizations on chromosome 17s carrying the Hairpain tail (Thp) deletion of the T locus since this deletion has been associated with sex reversal and hermaphroditism. We did not detect a significant decrease in the amount of hybridization of GATA/GACA repeats to the Thp deletion. In addition, three Bkm-positive cosmids from proximal chromosome 17 did not contain sequences deleted in Thp or TOrl and a fetal testes cDNA probe did not hybridize to the cosmid sequences. Although we confirmed the localization of Bkm-related sequences on chromosome 17, we were not able to relate GATA/GACA sequences on chromosome 17 to sex determination in mice.


Development of a Microscale Thermophoresis-Based Method for Screening and Characterizing Inhibitors of the Methyl-Lysine Reader Protein MRG15.
MRG15 is a transcription factor containing the methyl-lysine reader chromodomain. Despite its involvement in different physiological and pathological states, to date the role of this protein has not been fully elucidated due to the lack of a specific and potent chemical probe.In this work, we report the development of a microscale thermophoresis (MST)-based assay for the study of MRG15-ligand binding interactions. After the development, the assay was validated using a small focused library and UNC1215 as the reference compound, to yield the identification of 10 MRG15 ligands with affinities ranging from 37.8 nM to 59.1 µM.Hence, our method is robust, convenient, and fast and could be applied to other methylation reader domain-containing proteins for the identification of new chemical probes.


Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.
Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress.


Optimized arterial trees supplying hollow organs.
Computer models of arterial trees can be generated from optimization principles using the algorithm of constrained constructive optimization (CCO). Up to now this algorithm could handle only tissue areas of convex shape, without concavities. CCO is now generalized to cope also with non-convex organ shapes, possibly featuring external as well as internal concavities. This allows the modeling of a much larger class of interesting real arterial systems. The concept of a generalized domain-potential was developed to represent arbitrary non-convex shapes mathematically and incorporate them as boundary conditions to optimization. Domain-potentials may be derived from analytical representations as well as from finite element triangulations obtained from organ images. To demonstrate the feasibility of the concept, the optimized growth of an arterial tree model is confined to some part of an elliptical shell, representing the free wall of the left ventricle of the heart.


Advances in downstream processes and applications of biological carboxylic acids derived from organic wastes.
Recovering carboxylic acids derived from organic wastes from fermentation broth is challenging. To provide a reference for future study and industrial application, this review summarized recent advances in recovery technologies of carboxylic acids including precipitation, extraction, adsorption, membrane-based processes, etc. Meanwhile, applications of recovered carboxylic acids are summarized as well to help choose suitable downstream processes according to purity requirement. Integrated processes are required to remove the impurities from the complicated fermentation broth, at the cost of loss and expense. Compared with chemical processes, biological synthesis is better options due to low requirements for the substrates. Generally, the use of toxic agents, consumption of acid/alkaline and membrane fouling hamper the sustainability and scale-up of the downstream processes. Future research on novel solvents and materials will facilitate the sustainable recovery and reduce the cost of the downstream processes.


SURVEILLANCE OF CHILD DEVELOPMENT: AN ANALYSIS OF BRAZIL'S SITUATION.
To describe Brazil's historical background with regard to child development surveillance and perform a systematic review of studies published on surveillance records of child development within Child Health Handbooks. A literature review was conducted in April of 2016 in the following electronic databases: Latin American and Caribbean Literature in Health Sciences (LILACS), the Scientific Electronic Library Online (SciELO), and the Medical Literature Analysis and Retrieval System Online (Medline). The search did not have any language or publication period restrictions, and included the bibliographic references of the selected articles. The keywords "child development and child health records," and "child development and child health handbook" were applied. Articles were included that were original and that evaluated the use of child development surveillance tools in Brazil. Publications that were not original were excluded. The articles were selected first based on their title, then their abstracts, and finally a thorough reading. The recommendation to support child development surveillance has been occurring since 1984. In 1995, developmental milestones were included in the Child's Health Handbook, and in 2004 they became normative acts for surveillance, which should be carried out using this booklet. In the systematic review, six articles were selected in which the prevalence of child development surveillance recording ranged from 4.6 to 30.4%. This variation was due to different criteria and sample sizes as well as different methodologies employed to analyze the adequacy of filling out the handbook. Despite the fact that the Brazilian Ministry of Health formalized child development surveillance 32 years ago, the act of recording the surveillance in the Child Health Handbook is still deficient and irregular.


Acute nonrheumatic myopericarditis associated with group A hemolytic streptococcal tonsillitis in a male ICU-nurse.
We present the case of a 38-year-old man who developed acute myopericarditis, mimicking acute myocardial infarction, as manifested by electrocardiographic, echocardiographic alterations and elevated cardiac enzymes complicating Lancefield group A beta-hemolytic streptococcal tonsillitis. After receiving oral penicillin, the clinical recovery was complete. Fever, tachycardia and chest discomfort resolved within a few days. Furthermore, enzyme levels and C-reactive protein returned to normal within eight days.


Medical insurance feasibility study. A technical summary.
There are risks of adverse outcomes to patients in the course of health care management. A study was undertaken to measure these outcomes in California for 1974. Secondary benefits of the study include new insights into the types and sources of disabilities caused by health care management and the development of new methods for carrying out generic adverse-outcome monitoring.


Profound thrombocytopenia and survival of hematopoietic stem cell transplant patients without clinically significant bleeding, using prophylactic platelet transfusion triggers of 10 x 10(9) or 20 x 10(9) per L.
A trigger of 10 x 10(9) per L for prophylactic platelet (PLT) transfusions is generally recommended for stable thrombocytopenic patients who receive chemotherapy, based on studies showing similar incidence, severity, and fatality of bleeding compared with the 20 x 10(9) per L trigger. The outcome of thrombocytopenic nonbleeding patients has not been well described. This retrospective analysis evaluates thrombocytopenia and survival of 381 hematopoietic stem cell transplant (HSCT) patients without clinically significant bleeding, with 10 x 10(9) and 20 x 10(9) per L prophylactic triggers. A total of 170 patients who received prophylactic PLT transfusions at 20 x 10(9) per L (1997-1998, SP1) and 211 patients who had prophylaxis at 10 x 10(9) per L (1999-2001, SP2) were identified as nonbleeding patients. PLT counts and clinical complications were assessed within 100 days from HSCT. PLT counts less than or equal to 10 x 10(9) per L were found in 69.2 percent of patients in SP2 and 38.3 percent in SP1 (p < 0.001). Profound thrombocytopenia (4+ PLT counts <or=10 x 10(9)/L) was found in 19.0 percent of patients in SP2 and 7.0 percent in SP1 (p = 0.001). Patients with profound thrombocytopenia had significantly increased early mortality (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.25-8.07) and significantly reduced overall survival (hazard ratio [HR], 1.95; 95% CI, 1.28-2.97) compared to patients with 0 to 3 PLT counts less than or equal to 10 x 10(9) per L. The association of profound thrombocytopenia with early mortality was more notable in SP2. The 10 x 10(9) per L transfusion trigger is associated with significantly greater exposure to low PLT counts. Nonbleeding patients with profound thrombocytopenia were at significantly greater risk of dying compared with nonthrombocytopenic patients. These results suggest that safety of the 10 x 10(9) per L trigger should be more thoroughly evaluated.


Slow evolution of Europa's interior: metamorphic ocean origin, delayed metallic core formation, and limited seafloor volcanism.
Europa's ocean lies atop an interior made of metal and silicates. On the basis of gravity data from the Galileo mission, many argued that Europa's interior, like Earth, is differentiated into a metallic core and a mantle composed of anhydrous silicates. Some studies further assumed that Europa differentiated while (or soon after) it accreted, also like Earth. However, Europa probably formed at much colder temperatures, meaning that Europa plausibly ended accretion as a mixture containing water-ice and/or hydrated silicates. Here, we use numerical models to describe the thermal evolution of Europa's interior assuming low initial temperatures (~200 to 300 kelvin). We find that silicate dehydration can produce Europa's current ocean and icy shell. Rocks below the seafloor may remain cool and hydrated today. Europa's metallic core, if it exists, may have formed billions of years after accretion. Ultimately, we expect the chemistry of Europa's ocean to reflect protracted heating of the interior.


Correction: AGO Recommendations for the Surgical Therapy of the Axilla After Neoadjuvant Chemotherapy: 2021 Update.
[This corrects the article DOI: 10.1055/a-1499-8431.].


Study Protocol of a Prospective Multicenter Observational Study Evaluating Acute Lower Limb Ischemia.
Acute lower limb ischemia (ALI) is a limb- and potentially life-threatening condition which requires urgent evaluation and treatment. Contemporary data on optimal therapy and prognosis of ALI are lacking, while surgical, hybrid, and foremost endovascular techniques have rapidly evolved over the past decades. Available clinical guidelines are not based on high-level evidence and do not fully reflect day-do-day practice. Contemporary data on etiology, procedural strategies as well as patient outcomes in ALI are urgently needed to improve care and prevent limb loss. The current study was initiated by the European Vascular Research Collaborative (EVRC), established by young European vascular specialists, and aims to provide insight into contemporary treatment strategies in ALI and its clinical results within Europe. In this manuscript we report the rationale and a detailed study protocol. The proposed study is a prospective, international, multicenter, observational study on ALI (PROMOTE-ALI) (ClinicalTrials.gov - NCT05138679). Patients with ALI (Rutherford classification grade I -III) of one or both lower extremities will be included in the study. The primary endpoint of the study is amputation-free survival (AFS) at 30 d. Secondary endpoints are freedom from target limb reintervention, freedom from complications, clinical outcome of the index leg, and limb salvage and survival at 30 and 90 d after diagnosis of ALI. ALI remains a challenging condition and due to the heterogeneous etiology, clinical presentation and treatment strategies, a large multicenter study on this topic is needed to gain contemporary data on clinical outcomes and prognosis, especially for modern endovascular techniques. PROMOTE-ALI is expected to provide these data and set a benchmark for future randomized controlled trials (RCTs).


Identification and functional characterization of the novel isoforms of bovine norepinephrine transporter produced by alternative splicing.
Analyzing variation of bovine norepinephrine transporter (NET) at the 3'-region by RT-PCR in the adrenal glands and the brain revealed four isoforms of NET produced by alternative splicing of four cassettes (C0, C1, C2 and C3) encoded by exons 12-15, designated bNET1a (C0-C1-C2, formerly designated bNET1), bNET1b (C0-C2), bNET2a (C0-C1-C3) and bNET2b (C0-C3, formerly designated bNET2), respectively. Expression of these isoforms in COS-7 cells revealed that the isoforms that contain the C1 cassette encoded by exon 13 (bNET1a and bNET2a) showed a significant increase in [(3)H]norepinephrine uptake and [(3)H]nisoxetine binding, whereas the isoforms which lack the C1 cassette (bNET1b and bNET2b) failed to display those activities despite the selection of either exon 14 or exon 15. These results suggest that the region encoded by exon 13 is indispensable for NET functional expression.


High-glucose concentration aggravates TNF-alpha-induced cell viability reduction in human CD146-positive periodontal ligament cells via TNFR-1 gene demethylation.
Periodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high-glucose concentrations aggravate cell viability reduction in human CD146-positive PDLCs (CD146+ PDLCs) under tumor necrosis factor-alpha (TNF-alpha) induction. CD146+ PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10 ng/ml of TNF-alpha and 30 mM glucose. Cell viability was detected using Cell Counting Kit-8 assays and Luminescent Cell Viability Assays. Western blotting and real-time polymerase chain reaction were performed to determine tumor necrosis factor-alpha receptor-1 (TNFR-1) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR-1 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high-glucose concentration and TNF-alpha. Treatment with 30 mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR-1. Additionally, we found that the CpG island located within the TNFR-1 gene was hypomethylated under 30 mM glucose conditions. S-adenosylmethionine, an established methyl donor, reversed TNFR-1 upregulation and restored cell viability against high-glucose concentration and TNF-alpha. In conclusion, the present findings suggest that high-glucose-induced CpG island hypomethylation within the TNFR-1 gene plays an essential role in TNFR-1 upregulation, and this further enhances the cell viability reduction of CD146+ PDLCs caused by TNF-alpha.


Identification of epithelialization in high transsphincteric fistulas.
At present, transanal advancement flap repair (TAFR) is the treatment of choice for transsphincteric fistulas passing through the upper and middle third of the external anal sphincter. It has been suggested that epithelialization of the fistula tract contributes to the failure of the treatment. The aim of this study was to assess the prevalence of epithelialization of the fistula tract and to study its effect on the outcome of TAFR and TAFR combined with ligation of the intersphincteric fistula tract (LIFT). Forty-four patients with a high transsphincteric fistula of cryptoglandular origin underwent TAFR. Nine of these patients underwent a combined procedure of TAFR with LIFT. In all patients the fistula tract was excised from the external opening up to the outer border of the external anal sphincter. In patients undergoing TAFR combined with LIFT an additional central part of the intersphincteric fistula tract was excised. A total of 53 specimens were submitted. Histopathological examination of the specimens was carried out by a pathologist, blinded for clinical data. Epithelialization of the distal and intersphincteric fistula tract was observed in only 25 and 22% of fistulas, respectively. There was no difference in outcome between fistulas with or without epithelialization. Epithelialization of high transsphincteric fistulas is rare and does not affect the outcome of TAFR and TAFR combined with LIFT.


Prognostication of out-of-hospital cardiac arrest patients by 3-min end-tidal capnometry level in emergency department.
To evaluate the role of initial ETCO2 value in prognostication of OHCA patients in an Asian-Chinese cohort. Prospective cohort study. Emergency departments of two regional hospitals in a cluster of Hong Kong. Patients were recruited prospectively from the local cardiac arrest registry from July 2012 to June 2013. Patients of non traumatic OHCA aged ≥18 years old were included. Patients of OHCA presented with postmortem changes, those who decided for Do Not Resuscitate (DNR), regained pulse before arrival, or those without proper documentation of ETCO2 would be excluded. Primary outcome was return of spontaneous circulation (ROSC). A 3-min ETCO2 >10mmHg was a predictor of ROSC with OR 18.16 (95% CI 4.79-51.32, p<0.001). The diagnostic accuracy of 3-min ETCO2 >10mmHg to predict ROSC: sensitivity was 0.95 (95% CI 0.89-0.98) while the specificity was 0.27 (95% CI 0.21-0.33). Positive predictive value was 0.40 (95% CI 0.34-0.46) while negative predictive value (NPV) was 0.92 (95% CI 0.82-0.97). Area under ROC curve of 3-min ETCO2 predicting ROSC was 0.80 (95% CI 0.71-0.91). A 3-min ETCO2 ≤10mmHg was associated with poor prognosis and low chance of ROSC. Low ETCO2 level may have a role to reduce prolonged medically futile resuscitation.


A functional promoter polymorphism in interleukin-10 gene influences susceptibility to endometriosis.
To investigate the involvement of inflammation in the development of endometriosis. Case-control study to investigate the association between endometriosis and four inflammation-related genes: interleukin (IL)-6, IL-10, IL-1 beta, and cyclooxygenase-2. University hospital. We had 196 cases with pathologically proved endometriosis and 397 disease-free women as control subjects. A total of 12 single nucleotide polymorphisms (SNPs) were selected for genotyping, including functional SNPs and common tagging SNPs. Logistic regression and haplotype analyses were performed to evaluate the genetic effect with adjustment for other covariates. Genotypes at each SNP were in Hardy-Weinberg equilibrium in either case or control subjects, except for rs1800871 at IL-10 in the case subjects (P=.04). We found that the individuals carrying minor allele C of a functional promoter SNP rs1800871 at IL-10 was associated with a reduced risk by approximately twofold compared with the common TT genotype. The T allele was reported to have a lower gene expression level than the C allele, suggesting inadequate suppression of inflammation leading to endometriosis development. Haplotype analysis of the IL-10 gene did not yield a better result. Other genes were not associated with endometriosis. This study suggests that the functional promoter polymorphism at IL-10 may play a role in the development of endometriosis.


High-pressure infrared spectroscopy of ether- and ester-linked phosphatidylcholine aqueous dispersions.
Infrared spectra of aqueous dispersions of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and its ether-linked analogue, 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DHPC), were measured in a diamond anvil cell at 28 degrees C as a function of pressure up to 20 kbar. Although these two lipids differ only in the linkages to the saturated hydrocarbon chains, significant differences were observed in their barotropic behavior. Most notable were the magnitudes of the pressure-induced correlation field splittings of the methylene scissoring and rocking modes, and the relative intensities of the corresponding component bands. In the case of the scissoring mode, not only can the correlation field component band be resolved at a lower pressure in DHPC (1.2 kbar, as compared with 2.2 kbar in DPPC), but the initial magnitude of the correlation field splitting in DHPC, particularly less than 9 kbar, is significantly greater than that observed in DPPC. These differences are attributed to the presence of an interdigitated lamellar gel phase in DHPC. At all pressures where the correlation field component band delta'CH2 can be resolved, the relative peak height/intensity ratio R = I delta'/I delta is greater in DPPC than in DHPC, suggesting that this parameter may be useful as a test of interdigitation.


[Colonic lipoma: case report and literature review].
Colonic lipoma is a rare benign tumor infrequently met in clinical practice. We report a case of symptomatic lipoma of the ascending colon in a 61-year-old woman. Diagnosis was suspected on CT scan. Colotomy with lipectomy was performed. The diagnosis was confirmed by histological examination. Reviewing the literature and combining with our experience, we discuss the clinical features, diagnosis and treatment of this uncommon disease.


The relative significance of trabecular and cortical bone density as a diagnostic index for osteoporosis.
The density of the distal radius in the non-dominant forearm was measured non-invasively by Compton spectrometry in 234 post-menopausal women. The density of the trabecular tissue was determined almost independently from that of cortical tissue by horizontal and vertical scanning of the bone. It was found that the lower the density of the trabecular bone, the greater the difference between the density of the cortical and trabecular bone. As osteoporosis progresses, trabecular bone density in the distal radius seems to decrease faster than that of compact bone. Hence the severity of the disease is best determined by measuring the density of trabecular bone.


Cyanamide mediated syntheses under plausible primitive earth conditions. III. Synthesis of peptides.
Peptides were formed in yields of 5%, 17% and 66%, respectively, when aqueous solutions of glycine, isoleucine or phenylalanine were dried and heated for 24 h at 90 degrees C with adenosine 5'-triphosphate, 4-amino-5-imidazolecarboxamide and cyanamide. Glycine and L-phenylalanine produced mixtures of di-, tri- and tetrapeptides, while L-isoleucine gave only the dipeptide in detectable quantities. The dipeptides of L-isoleucine and L-phenylalanine were identified by mass spectrometry and enzymatic and enzymatic degradation.


Growth hormone-stimulated IGF-1 generation in cirrhosis reflects hepatocellular dysfunction.
Previous studies reported decreased serum IGF-1 levels in cirrhosis. We aimed to correlate GH-stimulated IGF-1 responses with both MELD and Child-Pugh scores and determine the impact of portal hypertension and nutrition on IGF-1 responses. Fifty-three patients (56+/-2 yrs) with cirrhosis were enrolled. Serum IGF-1 levels were measured by RIA before and 24h after a single injection of GH (0.06 mg/kg). Compared to controls, basal IGF-1 levels were significantly decreased in patients with cirrhosis (17.3+/-6.3 vs 13.6+/-5.1, P<0.001). Increments in IGF-1 levels were significantly lower in cirrhotic patients (controls: 133% vs 49% in MELD score <10, 38% in MELD score 11-18, and 13% in MELD score 19-24, p<0.001). 37% of patients had blunted IGF-1 responses. Increments in IGF-1 levels correlated with albumin (r=0.6), portal congestive index (r=0.4), and MAMC (r=0.25). By multivariate analysis, only CP (OR 5.7) and MELD scores (OR 4.5) accurately differentiated between blunted or non-blunted IGF-1 responses and not portal hypertension (OR 0.9) or malnutrition (OR 1.35). Cirrhosis is associated with low IGF-1 levels and an attenuated response to exogenous GH. These findings correlate better with the extent of hepatic dysfunction rather than the presence of portal hypertension or malnutrition.


Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients.
Resminostat is an oral inhibitor of class I, IIB, and IV histone deacetylases. This phase I/II study compared the safety and efficacy of resminostat plus sorafenib versus sorafenib monotherapy as first-line therapy for advanced hepatocellular carcinoma (HCC). In phase I, resminostat (400 mg or 600 mg/day on days 1 to 5 every 14 days) was administered with sorafenib (800 mg/day for 14 days) to determine the recommended dose for phase II. In phase II, patients were randomized (1:1) to sorafenib monotherapy or resminostat plus sorafenib. The primary endpoint was time-to-progression (TTP). Nine patients (3: 400 mg, 6: 600 mg) were enrolled in phase I, and the recommended dose of resminostat was determined to be 400 mg/day. Then 170 patients were enrolled in phase II. Median TTP/overall survival (OS) were 2.8/14.1 months with monotherapy versus 2.8/11.8 months with combination therapy (Hazard Ratio [HR]: 0.984, p = 0.925/HR: 1.046, p = 0.824). The overall incidence of adverse events was similar in both groups (98.8% versus 100.0%). However, thrombocytopenia ≥ Grade 3 was significantly more frequent in the combination therapy group (34.5% versus 2.4%, p < 0.001). Subgroup analysis revealed that median TTP/OS was 1.5/6.9 months for monotherapy versus 2.8/13.1 months for combination therapy (HR: 0.795, p = 0.392/HR: 0.567, p = 0.065) among patients with a normal-to-high baseline platelet count (≥ 150 × 103/mm3). In patients with advanced HCC, first-line therapy with resminostat at the recommended dose plus sorafenib showed no significant efficacy advantage over sorafenib monotherapy.


Partial meniscectomy using needle arthroscopy associated with significantly less pain and improved patient reported outcomes at two weeks after surgery: A comparison to standard knee arthroscopy.
to compare immediate post-operative pain and patient-reported outcomes (PROs) after partial meniscectomy with needle (NA) vs. standard (SA) arthroscopy technique. A retrospective review of a consecutive series of patients who underwent partial meniscectomy before and after adoption of a needle arthroscopic technique was performed. Meniscus repairs, root repairs, and those with ligamentous injuries were excluded. Total milligram morphine equivalents (MMEs) consumed, Visual analog scale (VAS) pain, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) were compared pre-operatively and at 2 and 6-weeks postoperatively. Univariate analysis was used to compare results. Nineteen patients were in each group (NA: 10 females, SA: 11 females). Mean ± SD age (NA 42.8 ± 8.4 vs. SA 47.6 ± 10.4 years, p = 0.13) and body mass index (NA 31.4 ± 5.6 vs. SA 35.1 ± 5.4 m/kg2, p = 0.06) were not significantly different. Seventeen (89%) patients in both groups had medial meniscus tears of the posterior horn. Preoperative Outerbridge score was significantly greater in the SA group (3.4 vs. 1.8, p = 0.002); however, preoperative VAS pain (NA 6.1 ± 1.7 vs. SA 6.1 ± 1.8, p = 0.98) and KOOS pain (NA 44 ± 17% vs. SA 37 ± 12.5%, p = 0.20) were similar. Amount of arthroscopic fluid used was significantly greater in the SA vs. NA group (1.4 ± 0.7 vs. 0.5 ± 0.3 L, p < 0.0001), but tourniquet time was equivalent (NA 20 ± 6 vs.16 ± 6 min, p = 0.11). VAS pain scores (NA 1.0 ± 1.1 vs. SA 2.6 ± 1.5, p = 0.0014), KOOS pain (NA 79 ± 15% vs. 58 ± 19%, p = 0.0006), and Quality of Life (QOL) scores (NA 70 ± 22% vs. SA 43 ± 24%, p = 0.001) were significantly better at 2-weeks post-op in the N group. By 6 weeks post-op, all PROs including VAS pain and KOOS scores were similar between groups. Adoption of a needle arthroscopic technique for partial meniscectomy was associated with significantly improved VAS and KOOS pain scores two-weeks post-operatively. Differences were not sustained at 6 weeks after surgery. III, Retrospective Comparison Study.


Superior mesenteric artery first approach can improve the clinical outcomes of pancreaticoduodenectomy: A meta-analysis.
Superior mesenteric artery (SMA) first approach was a new improvement for pancreaticoduodenectomy (PD), but there is no evidence whether this approach is advantageous to PD. This meta-analysis aimed to determine the effects of the superior mesenteric artery (SMA) first approach on outcomes of pancreaticoduodenectomy (PD). Literature searches were conducted on PubMed, The Cochrane Library, EMBASE, Web of Science, Clinical Trials Registry and China Biology Medicine disc. We completed a meta-analysis of the SMA first approach in PD, assessing overall survival, R0 resection, blood loss, postoperative complications, operation time and postoperative stay. The odds ratios and weighted mean differences with 95% confidence intervals (CIs) were pooled. Eighteen studies comprising 1483 participants were included. Patients who received SMA-PD had significantly lower overall complication rate (OR 0.62, 95% CI 0.47 to 0.81, P = 0.001) and less blood loss (WMD -264.84, 95% CI -336.1 to -193.58, P < 0.001). The obviously increased R0 resection rate (OR 2.92, 95% CI 1.72 to 4.96, P < 0.001) and 3-year OS (OR 2.15, 95% CI 1.34 to 3.43, P = 0.001) were found in the SMA-PD group. The SMA-PD group had better clinical outcomes, particularly in long-term survival of pancreatic cancer patients; furthermore, the patients acquired superior clinical efficacy via the posterior approach in SMA-PD.


Impairment of CO2 reactivity in severe head injury patients: an investigation using thermal diffusion method.
For measurement of the cerebral blood flow (CBF) the thermal diffusion method is quite convenient and allows the chronological measurement of CBF and CO2 reactivity of cerebral vessels. We investigated the CO2 reactivity of fifteen head injury patients. The results showed that in head injury cases, the disturbance of the CO2 reactivity correlates well to poor outcome. Using thermal diffusion method, investigations of CO2 reactivity are useful for further understanding of the physiological state of head injury patients.


Prevention of irrigant absorption during TURP: continuous low-pressure irrigation.
Comparative studies have been carried out on bladder pressure. The pressure gradient between bladder and abdominal cavity during TURP proved to be significantly lower with continuous low-pressure irrigation than with conventional high-pressure irrigation. Absorption is reduced to a clinically insignificant rate, as shown by blood sugar determinations during TURP in 100 cases.


The influence of serum folate on urinary excretion of vitamin B12.
It was found that in patients with decreased serum folate concentration, urinary excretion of vitamin B12 was increased in a statistically highly significant way with both oral administration of 58 Co-labeled vitamin B12 and with a 57Co-labeled vitamin B12 intrinsic factor complex. This increased vitamin B12 excretion may account for some false normal Schilling test results. Furthermore, in folate deficiency, the intrinsic factor no longer seems required for vitamin B12 to pass the intestinal wall. It is also questionable whether vitamin B12 absorbed through the intestine under these circumstances could be properly metabolized. Besides statistical evidence, some clinical support for this theory is presented. These findings offer a possible clue for some literature reports that have lacked a satisfactory explanation.


Microcalorimetric investigations on human leukemia cells--Molt 4.
Heat production by leukemia cells Molt 4, growing in suspensions with 1 and 3 x 10(5) cells/ml for 4 days, was studied by microcalorimetry. Heat production rates were related to cell growth, glucose consumption, lactate production and cellular ATP-content. The results show that the time course of heat dissipation is dependent on initial cell number. However, observed thermal power maxima were fairly identical in all experiments. Heat production rates per cell were similar during the initial phase of the study independently of initial cell number, while higher cell densities resulted in significantly lower rate of heat production. Glycolytic conversion of glucose into lactate is nearly stoichiometric. Our results indicate a relationship between heat production and amounts of glucose and lactate in the medium. ATP concentration in cells decreased after 24 hours of culture.


Eating behaviour of Indonesian adolescents: a systematic review of the literature.
Global evidence has shown that behaviour acquired during adolescence often lasts into adulthood. Diet quality of and malnutrition in Indonesian adolescents is a neglected area of research. The current study reviews all studies related to eating behaviour in Indonesian adolescents to support evidence-based policy to improve diets. We searched electronic databases (six international and one local), from January 2000 to April 2018. The search terms used were (1) prevalence (prevalence OR number* OR case*, incidence OR survey), (2) adolescents (adolescen* OR school-age OR young adult), (3) Indonesia (Indonesia*) and (4) eating pattern (eat* OR fruit OR vegetable OR food recall OR food OR frequenc* OR consumption OR dietary intake). Articles were assessed against a critical appraisal tool. Indonesia. 10-19 years. We discovered 15 studies related to eating behaviour, 5 of which were secondary analyses of nationally representative surveys and one was a nationwide survey. Of the nine studies, one study was conducted in multiple cities, and the rest were conducted in a single city or smaller area. There were seven main topics from the included studies: nutrient adequacy, fruit and vegetable consumption, water and beverage intake, Na intake, breakfast habit, snacking frequency and western fast food consumption. Adolescents consume inadequate amounts of protein, fruits and vegetables, and excessive amounts of Na and western fast food. Measures are needed to improve and motivate adolescents to adopt healthier eating patterns. Furthermore, there is a need to have one standard definition and measurement of eating behaviour in Indonesia.


Low-dimensional embedding of fMRI datasets.
We propose a novel method to embed a functional magnetic resonance imaging (fMRI) dataset in a low-dimensional space. The embedding optimally preserves the local functional coupling between fMRI time series and provides a low-dimensional coordinate system for detecting activated voxels. To compute the embedding, we build a graph of functionally connected voxels. We use the commute time, instead of the geodesic distance, to measure functional distances on the graph. Because the commute time can be computed directly from the eigenvectors of (a symmetric version) the graph probability transition matrix, we use these eigenvectors to embed the dataset in low dimensions. After clustering the datasets in low dimensions, coherent structures emerge that can be easily interpreted. We performed an extensive evaluation of our method comparing it to linear and nonlinear techniques using synthetic datasets and in vivo datasets. We analyzed datasets from the EBC competition obtained with subjects interacting in an urban virtual reality environment. Our exploratory approach is able to detect independently visual areas (V1/V2, V5/MT), auditory areas, and language areas. Our method can be used to analyze fMRI collected during "natural stimuli".


Double half-cone flap umbilicoplasty: a new technique for the proboscoid umbilical hernia in children.
Although many techniques have been described for reconstruction of the protruding umbilicus in children with umbilical hernia, we present a simple new technique for umbilicoplasty. Ten children (six males and four females) with umbilical hernias and protruding skin were operated upon. Operative description consists of amputation of the protruding umbilical skin, leaving two unequal half-cones, a short cephalic half-cone (0.5 cm) and a long caudal half-cone (1 cm). These two half-cones are fashioned, closed, and inverted to constitute the new umbilicus following a classic hernia repair. The early results were excellent in all cases with no infection and no ischaemic changes encountered in the skin of the reconstructed umbilicus. Follow-up periods between 6 and 18 months revealed a cosmetically pleasing shape of the umbilicus. Only one case developed hypertrophy of the resulting scar. We present our initial experience with the new technique. This new technique provides a good solution for reconstruction of the protruding umbilical skin. Our double half-cone flap umbilicoplasty technique is easy to learn and to perform.


Assessing the knowledge, attitudes, practices, and perspectives of stakeholders of the deworming program in rural Rwanda.
Worm infections are among the most prevalent neglected tropical diseases worldwide. Schistosomiasis and soil-transmitted helminths infections, most common worm infections affecting Rwandan school-aged children, are addressed by the national deworming program since 2014. To date, no published studies have assessed the knowledge, attitudes, and practices of the key implementers of the national deworming program conducted at village and school level in Rwanda. This study aimed to assess key stakeholders' knowledge, attitudes, practices, and perspectives about the decentralized national deworming program. We carried out a quantitative, cross-sectional study with complementary in-depth interviews in two districts of Rwanda in June 2021. From the 852 surveyed community health workers and teachers, 54.1% had a knowledge score considered good (≥80%). The mean knowledge score was 78.04%. From the multivariate analysis, lack of training was shown to increase the odds of having poor knowledge (OR 0.487, 95% CI: 0.328-0.722, p <0.001). The in-depths interviews revealed poor water access and hesitance from caregivers as perceived challenges to the success of the deworming program. Our findings demonstrate the importance of training community health workers and schoolteachers on worm infections as they are the key implementers of the deworming program. This would enhance their capacity to provide health education and sensitization on misconceptions and misinformation towards deworming. Moreover, research is needed to assess the impact of poor access to water, sanitation and hygiene facilities on the prevalence of worm infections in Rwanda.


Characterization of normal peripheral blood T- and B-cell colony-forming cells: growth factors(s) and accessory cell requirements for their in vitro proliferation.
The biological properties of normal peripheral lymphoid precursors were studied using separate colony assays for T- and B-cell colony-forming cells (T-CFC and B-CFC, respectively). Cell fractions, selected by complement-mediated cytotoxicity with monoclonal antibodies, were cultured in methylcellulose using different sources of growth factors containing (PHA-LCM2 and PHA-LCM7) or not (PHA-TCM) Interleukin-2 (IL-2). Well-differentiated T-cell colonies were only observed with IL-2-containing conditioned media (CM). Normal T-CFC displayed either an immature (E-T11-OKT3-Ia-) or mature (E+) phenotype, were quiescent cells presenting different radiosensitivity (D0 = 80 and 155 rads, respectively). B-CFC displayed the E-T11-OKT3-B1-Ia+ surface phenotype, were in DNA synthesis and were more radioresistant (D0 = 300 rads) than T-CFC. B-cell colonies could be obtained in the presence of allogeneic irradiated T cells and PHA-TCM, but not with IL-2-containing CM. When E-T11-OKT3- cells were seeded with PHA-TCM supplemented with increasing amounts of semipurified IL-2 in the presence of a fixed number of irradiated T cells, the B-cell colony growth (as assessed by the frequency of sIg+ colony cells) progressively decreased whereas that of T-cell colonies increased. IL-2-free CM (PHA-TCM) was able to induce T-cell colony growth from E-T11-OKT3- cells but addition of allogeneic irradiated T cells induced B-cell colony formation in a dose-dependent manner. Conversely, T cells enhanced T-cell colony growth in the presence of IL-2-containing CM. Furthermore, adherent cell depletion of E-T11-OKT3- cells inhibited T- but not B-cell colony growth. These results taken together suggest that T- and B-cell colonies derive from different progenitor cells which have different growth factor(s) and accessory cell requirements and indicate that T-cell colony growth is associated with inhibition of B-cell colony formation.


Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency.
Arginine:glycineamidinotransferase (AGAT/GATM) deficiency has been described in 9 patients across 4 families. Here we describe the clinical outcome and response to creatine supplementation in a patient of the second family affected with AGAT deficiency-a 9-year-old girl. Delayed motor milestones were noticed from 4 months of age and at 14 months moderate hypotonia, developmental delay and failure to thrive. Laboratory studies revealed low plasma creatine as well as extremely low levels of guanidinoacetic acid in urine and plasma. Proton magnetic resonance spectroscopy (MRS) of the brain showed absence of creatine. DNA sequence analysis revealed a homozygous mutation (c.484+1G>T) in the AGAT/GATM gene. AGAT activity was not detectable in lymphoblasts and RNA analysis revealed a truncated mRNA (r.289_484del196) that is degraded via Nonsense Mediated Decay. At 16 months, Bayley's Infant Development Scale (BIDS) showed functioning at 43% of chronologic age. Oral creatine supplementation (up to 800 mg/kg/day) was begun. At age 9 years she demonstrated advanced academic performance. Partial recovery of cerebral creatine levels was demonstrated on MRS at 25 months of age. Brain MRS at 40 months of age revealed a creatine/NAA ratio of about 80% of that in age-matched controls. 8 years post initiation of oral creatine supplementation, patient demonstrates superior nonverbal and academic abilities, with average verbal skills. We emphasize that early diagnosis combined with early treatment onset of AGAT deficiency may lead to improvement of developmental outcome.


A simple and rapid method for isolating myelin basic protein.
The conduction of impulses along axons of nerves is facilitated by the myelin sheath, composed of proteins and lipid. Myelin basic proteins (MBPs) are extrinsic membrane proteins that play an important role in the structural organization of the myelin sheath. In the central nervous system, MBPs account for 30-40% of total protein. The traditional method of MBP isolation involves the use of chloroform-ethanol, which would destroy the native form of MBP. A modified method for maintaining its native form was developed. The white matter of porcine brain was directly extracted by buffers containing different concentrations of sodium chloride owing to MBP solubilized at high concentration of NaCl. The MBP was further purified by cation exchange chromatography and buffers containing glycine and salts. Purified MBP were consistently obtained by this method.


Treatment of colored effluent of the textile industry in Bangladesh using zinc chloride treated indigenous activated carbons.
The adsorption of colored compounds from the textile dyeing effluents of Bangladesh on granulated activated carbons produced from indigenous vegetable sources by chemical activation with zinc chloride was studied. The most important parameters in chemical activation were found be the chemical ratio of ZnCl2 to feed (3:1), carbonization temperature (450-465 degrees C) and activation time (80 min). The adsorbances at 511 nm (red effluent) and 615 nm (blue effluent) were used for color estimation. It is established that at optimum temperature (50 degrees C), time of contact (30-40 min) and adsorbent loading (2 g l(-1)), activated carbons developed from Segun saw-dust and water hyacinth showed substantial capability to remove coloring materials from the effluents. It is observed that adsorption of reactive dyes by all sorts of activated carbons is higher than disperse dyes. It is explained that activated carbon, because of its acidic nature, can better adsorb reactive dye particles containing large number of nitrogen sites and -SO3Na group in their structure. The use of carbons would be economical, as saw-dust and water hyacinth are waste products and abundant in Bangladesh.


Age-related changes in the glutathione redox system.
The effect of aging on the glutathione redox system was evaluated in this study. For this purpose, we determined reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood, glutathione peroxidase (GPx) and glutathione reductase (GSSGR) in erythrocytes and selenium (Se) in plasma in 176 healthy individuals. We also calculated GSH/GSSG molar ratios. These subjects were divided into five groups: group 1 (n=25; 0.2-1 years old); group 2 (n=28; 2-11 years old); group 3 (n=23; 12-24 years old); group 4 (n=40; 25-40 years old); group 5 (n=60; 41-69 years old). GSH levels in groups 1 and 5 were significantly lower than the other groups (p<0.001). Conversely, GSSG levels were significantly high in these periods (p<0.001). The GSH/GSSG molar ratio was found to be low both in the first year of life and in the oldest group (p<0.001, respectively). GPx activity in group 5 was increased as compared to the other groups (p<0.001). GSSGR activity was significantly lower in the oldest groups than in the other groups (p<0.001). Se levels were found to be low in the oldest group (p<0.001). Selenium levels of women in group 5 were significantly high as compared to the men (p<0.01). We found negative correlations between age and GSH levels (r=0.402; p<0.001), selenium levels (r=0.454; p<0.001), GSH/GSSG molar ratio (r=0.557; p<0.001) and GSSGR activity (r=0.556; p<0.001). There were positive correlations between age and GPx (r=0.538; p<0.001) and GSSG level (r=0.551; p<0.001). In conclusion, our findings show that the glutathione redox system is affected by age. Oxidative stress increases during the aging process. There is no effect of aging on the glutathione redox system according to sex except for the Se level.


[The degradation on cultivated Gastrodia populations and prevention measures].
To propose views and concepts on the degradation of cultivated Gastrodia populations. The differences between natural and cultivated Gastrodia populations were compared and discussed in terms of their biological features, qualities and yields. There were changes and degradation in biological features and some important properties of yield in cultivated Gastrodia. The direct reason of cultivated Gastrodia degradation is the ecological disturbace of forests and the decreasing amount of natural Gastrodia populations; The indirect reason is manual pollination and other changes of the natural growing environment.


The roles of RGD and grooved topography in the adhesion, morphology, and differentiation of C2C12 skeletal myoblasts.
Both chemical and topographic cues are crucial for the development of skeletal muscle. In this study, the relative roles of both signals in regard to cell adhesion, morphology, and differentiation of C2C12 skeletal myoblasts were investigated. Grooved polystyrene substrates containing grooves with approximately 900 nm in width with 600 nm ridge spans and 665 nm in depth were conjugated with the cell adhesion peptide arginine-glycine-aspartic acid (RGD). RGD conjugation significantly enhanced the adhesion, growth and differentiation of C2C12 cells. On the other hand, anisotropic topography primarily directed the direction and alignment of myoblasts and myotubes. The results in this study provide information regarding the relative roles of chemical and topographic cues in musculoskeletal myogenesis, and are of interest to applications in muscle tissue engineering.


Who needs an ultrasound? Using patient symptom questionnaire & UTI history to determine when to obtain an RBUS in children with non-neurogenic lower urinary tract dysfunction.
Non-neurogenic lower urinary tract dysfunction (LUTD) is one of the most common reasons for presentation to a pediatric urologist, affecting up to 20% of children. Predicting who will benefit from RBUS as part of their work-up is challenging as the majority will have normal imaging. Our objective was to assess the utility of using the Dysfunctional Voiding and Incontinence Scoring System (DVISS) and urinary tract infection (UTI) history to predict which LUTD patients were most likely to have an abnormal RBUS as well as determine a DVISS cutoff to aid in making this prediction. We hypothesized that higher DVISS scores and a positive urinary tract infection (UTI) history would be associated with increased likelihood of RBUS abnormality. We retrospectively reviewed outpatients seen for LUTD from 5/2014-1/2016 who received an RBUS. Association between prior UTI, DVISS score, gender, and race and RBUS abnormality were evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curves were created to evaluate the predictive model and a Youden index calculated to determine the optimal cutoff for DVISS score to predict abnormal RBUS. 15 of 333 patients (4.5%) had a clinically significant RBUS abnormality. Significantly more patients with abnormal RBUS had a positive UTI history and median DVISS was higher. UTI history and DVISS score were associated with RBUS abnormality whereas neither gender nor race were. A DVISS score cutoff of 12 was determined to be ideal for predicting abnormal imaging. Using DVISS≥12 and positive UTI history, patients with both risk factors were significantly more likely to have an abnormal RBUS than those with zero or one risk factor (Figure). To the best of our knowledge this is the first study to try to identify risk factors associated with RBUS abnormality in pediatric LUTD patients and create an evidence-based approach to imaging these patients. We found both DVISS cutoff ≥12 and positive UTI history to be useful to risk stratify LUTD patients' likelihood of abnormal RBUS. Limitations include the study's retrospective nature as well as the fact the population was drawn from a tertiary care pediatric hospital with a large referral population and the fact that the decision to order an RBUS was based on individual clinician preference and decision making. We found that DVISS score≥12 and UTI history are useful in guiding the decision to obtain RBUS in pediatric LUTD patients.


Defence strategies adopted by the medicinal plant Coleus forskohlii against supplemental ultraviolet-B radiation: Augmentation of secondary metabolites and antioxidants.
Supplementary ultraviolet-B (ambient+3.6 kJ m(-2) day(-1)) induced changes on morphological, physiological, and biochemical characteristics (specifically the defence strategies: UV-B protective compounds and antioxidants) of Coleus forskohlii were investigated under field conditions at 30, 60, and 90 days after transplantation. Levels of secondary metabolites increased under s-UV-B stress; flavonoids and phenolics (primary UV-B screening agents) were recorded to be higher in leaves which are directly exposed to s-UV-B. This was also verified by enhanced activities of phenylpropanoid pathway enzymes: phenylalanine ammonia lyase (PAL), cinnamyl alcohol dehydrogenase (CAD), 4-coumarate-CoA ligase (4CL), chalcone-flavanone isomerase (CHI), and dihydroflavonol reductase (DFR). Antioxidants, both enzymatic (ascorbate peroxidase, catalase, glutathione reductase, peroxidase, polyphenol oxidase, and superoxide dismutase) and non-enzymatic (ascorbic acid and α-tocopherol) also increased in the treated organs of the test plant, higher contents being recorded in roots except for ascorbic acid. On the contrary, protein and chlorophyll content (directly implicated in regulating plant growth and development) declined under s-UV-B. These alterations in plant biochemistry led the plant to compromise on its photosynthate allocation towards growth and biomass production as evidenced by a reduction in its height and biomass. The study concludes that s-UV-B is a potent stimulating factor in increasing the concentrations of defense compounds and antioxidants in C. forskohlii to optimize its performance under stress.


Experiences and perceptions of nurses working night shift: a qualitative systematic review protocol.
The objective of this qualitative systematic review is to examine the available evidence on the experiences of nurses working the night shift within any specialty in the acute care, subacute, or long-term care setting. Nurses are required for round-the-clock patient care, and night shift nurses can experience detrimental effects as a result of their work hours. Understanding nurses' experiences when working night shift will facilitate the development of strategies to minimize the potential negative effects of working at night. In examining nurses' perceptions of working night shift, there is scope to explore how to improve night shift nurses' practice environment and job satisfaction, which will then translate to improved patient outcomes. This review will consider qualitative studies that include registered nurses and licensed practical nurses who work night shift or rotate between day and night shift. Night supervisors and advanced practice nurses will be excluded due to the potential for dissimilar experiences and resources within those groups. The search will be limited to studies published in English from 1983 to the present. The search strategy is designed to locate both published and unpublished qualitative studies by searching academic databases for published studies, gray literature, and hand searching reference lists. The study selection, critical appraisal, data extraction, and synthesis for this systematic review will be conducted in accordance with the JBI methodology for systematic reviews of qualitative evidence. PROSPERO CRD42019135294.