Use of the National Early Warning Score for predicting deterioration of patients with acute pulmonary embolism: a post-hoc analysis of the YEARS Study.
The Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. In haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. Of 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. In comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice.


Cervical cancer prevention in Africa: A policy analysis.
Cervical cancer is a major public health challenge in Africa. We analyzed the presence and content of policies for the primary, secondary and tertiary prevention of cervical cancer in Africa, to identify areas of opportunity for policy strengthening in the region most affected by cervical cancer globally. We searched for publicly-available policy documents among countries in Africa. Using a data extraction form, we gathered data from these policies about key elements of primary, secondary and tertiary prevention approaches and activities based on World Health Organization (WHO) guidelines. We also contacted key stakeholders in each country to confirm these details. We summarized each country's policy details (summed score for each prevention stage and overall), and compared these scores across individual countries and groups of countries based on economic, policy and public health characteristics. Most countries had at least one policy addressing some aspect of cervical cancer prevention. Primary and secondary prevention were more commonly addressed, and certain details like age of vaccination, screening age/interval and method, were frequently mentioned in these policies. Countries with high HIV burden and relatively more donor financing for health had more comprehensive cervical cancer policies; there was no apparent association with cervical cancer mortality, female representation in government, or economic indicators (poverty prevalence or income inequality). There is room to improve cervical cancer policy comprehensiveness in Africa, and to bring these policies in line with evidence and expert recommendations. This analysis is timely given upcoming monitoring of the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. These findings suggest some improvements in African cervical cancer policy, including increased inclusion of vaccination, but many topics remain under-specified. The influence of internal and external factors on policymaking should also be considered.


Total parenteral nutrition-associated cholestasis: clinical and histopathologic correlation.
Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infants and children. The pathogenesis of this syndrome is poorly understood. The aims of this study were: (1) to define the histologic liver injury in relation to the clinical course of infants on TPN and (2) to determine whether enteral feeding will reverse or halt these changes. We identified 31 infants treated for severe gastrointestinal disease for whom liver histology was available from 1987 to 1991. Clinical records and liver biopsy (23) or autopsy specimens (13) were reviewed. Five patients had biopsies at two subsequent operations. The clinical diagnosis was necrotizing enterocolitis (24), atresia or stenosis (3), midgut volvulus (2), Hirschsprung's disease (1), and sepsis (1). Twenty-one of 31 infants were premature and had a mean birth weight of 1,868 g. Twenty-five of 31 were on TPN and 28 of 31 had received some enteral feeding by the time of the biopsy. Enteral feeding was begun as early as possible in all infants even if continued TPN was necessary for full support. Cholestasis occurred in 71% of premature infants versus 22% of full-term babies. Infants with cholestasis had been on TPN for a longer time (37 days v 18) with a correspondingly shorter period of enteral feeding (17 days v 27). Mean total bilirubin level was 14 in patients with cholestasis and 5 in those without, but the bilirubin level did not correlate with the extent of histological injury and was frequently normal despite marked histological damage.(ABSTRACT TRUNCATED AT 250 WORDS)


Galanin receptor antagonists M40 and C7 block galanin-induced feeding.
Two peptide antagonists of the galanin receptor, M40 (galanin[1-13]-Pro-Pro-[Ala-Leu]2-Ala amide) and C7 (galanin[1-13]-spantide amide), significantly inhibited galanin-induced consumption of a palatable wet cookie mash, when microinjected intraventricularly to satiated rats. Antagonists were effective at doses equimolar to or less than the active doses of galanin. Feeding induced by an overnight fast was not significantly different in rats microinjected with saline as compared to M40 or C7, at doses which inhibited galanin-induced feeding. The activity of the chimeric compound, C7, did not appear to be linked to the properties of its C-terminal spantide-like sequence, as C7 did not induce barrel rolling at doses which inhibited galanin-induced feeding. The IC50 for displacement of 125I-[Tyr26]-porcine galanin 1-29 binding in rat hypothalamic membranes was 15 nM for M40, and 0.2 nM for C7, as compared to 0.8 nM for unlabelled porcine galanin(1-29). These two structurally different galanin antagonists, both demonstrating antagonist activity in vivo in awake, behaving rats, provide promising tools for further analyses of the functional activity of galanin in the mammalian brain.


Neurological and behavioral sequelae in children operated on for brain abscess.
In order to characterize neurological, intellectual and behavioral sequelae better after surgical treatment of brain abscess in childhood, 32 children were studied over a 10-year time span after treatment of a brain abscess. Depending on the clinical condition, surgical treatment consisted of simple aspiration through a burr hole or of total excision after craniotomy. There were only 3 postoperative deaths (9%). The scheduled time for long-term follow-up was 3 years after surgery. The patient assessment included information concerning the presence of seizures, accurate neurological examination, an EEG, and a battery of intellectual tests to evaluate the presence of behavioral-mental deficits. Late seizures developed in 7 of the 29 survivors. Five patients presented permanent hemiparesis after surgical treatment. It is noteworthy that the intellectual impairment observed was more severe in younger patients, while the behavioral disturbances were more marked in school-age children.


Growth kinetics of Listeria monocytogenes and spoilage microorganisms in fresh-cut cantaloupe.
The main objective of this study was to investigate the growth kinetics of Listeria monocytogenes and background microorganisms in fresh-cut cantaloupe. Fresh-cut cantaloupe samples, inoculated with three main serotypes (1/2a, 1/2b, and 4b) of L. monocytogenes, were incubated at different temperatures, ranging from 4 to 43 °C, to develop kinetic growth models. During storage studies, the population of both background microorganisms and L. monocytogenes began to increase almost immediately, with little or no lag phase for most growth curves. All growth curves, except for two growth curves of L. monocytogenes 1/2a at 4 °C, developed to full curves (containing exponential and stationary phases), and can be described by a 3-parameter logistic model. There was no significant difference (P = 0.28) in the growth behaviors and the specific growth rates of three different serotypes of L. monocytogenes inoculated to fresh-cut cantaloupe. The effect of temperature on the growth of L. monocytogenes and spoilage microorganisms was evaluated using three secondary models. For L. monocytogenes, the minimum and maximum growth temperatures were estimated by both the Ratkowsky square-root and Cardinal parameter models, and the optimum temperature and the optimum specific growth rate by the Cardinal parameter model. An Arrhenius-type model provided more accurate estimation of the specific growth rate of L. monocytogenes at temperatures <4 °C. The kinetic models developed in this study can be used by regulatory agencies and food processors for conducting risk assessment of L. monocytogenes in fresh-cut cantaloupe, and for estimating the shelf-life of fresh-cut products.


Development of Social Determinants of Health Screening Tool (SDoHST): qualitative validation with stakeholders and patients in South Australia.
It is well-established that social determinants of health contribute to health and well-being. Among the social determinants of health, health-related social needs (HRSNs) are unmet needs that can be identified by the health care system and addressed through referral to community services. Despite the importance of identifying patients with HRSNs, none of the few screening tools for HRSNs available internationally have received a comprehensive psychometric validation. This study aims to conduct a qualitative validation of the Social Determinants of Health Screening Tool (SDoHST). This study took place at Lyell McEwin Hospital, a major tertiary hospital located in Adelaide, South Australia. Patient (n = 5) and stakeholder (n = 9) focus groups were conducted face to face, audio recorded, and transcribed verbatim. Inductive content analysis of focus group transcripts was performed to inform tool modifications (e.g. item rewording). The patient focus group recommended the addition of an explanatory paragraph to improve face validity, and highlighted the importance of reliable transport and internet access. The stakeholder focus group recommended using language that carries less stigma to this particular community and incorporating questions surrounding cultural, linguistic, and spiritual needs. The final version of the SDoHST included 12 items (four original items were removed and seven new items were added during the validation process). The SDoHST is the first validated tool to measure social determinants of health (and specifically HRSNs) in Australia, receiving a comprehensive qualitative validation. The instrument is readily available and future studies will further investigate its psychometric properties with quantitative methods.


Electrooxidation as the anaerobic pre-treatment of fats: oleate conversion using RuO2 and IrO2 based anodes.
Electrochemical treatment of oleate using RuO2 and IrO2 type dimensionally stable anodes in alkaline medium was performed to develop a feasible anaerobic pre-treatment of fatty effluents. The results showed that the pre-treated solutions over RuO2 were faster degraded by anaerobic consortium than the raw oleate solutions or the electrolysed solutions using IrO2. In batch experiments carried out with pre-treated solutions over RuO2 (100-500mg/L), no lag phases were observed before the methane production onset. On the other hand, raw oleate and pre-treated oleate over IrO2 had originated lag phases of 0-140 and 0-210h, respectively. This study demonstrated that it is advantageous to apply the electrochemical treatment carried out on the RuO2 type DSA in order to achieve a faster biodegradation of lipid-containing effluent and consequently to obtain a faster methane production.


Ligustilide, a novel SIRT1 agonist, alleviates lipopolysaccharide-induced acute lung injury through deacetylation of NICD.
Development and progression of sepsis-induced acute lung injury (ALI) involve apoptosis and oxidative stress in lung epithelial cells. Ligustilide (LIG) is one of the main bioactive constituents derived from the Angelica sinensis. As a novel SIRT1 agonist, LIG owns powerful anti-inflammatory and antioxidative properties, exerting remarkable therapeutic effects on cancers, neurological disorders, and diabetes mellitus. However, whether LIG could protect against lipopolysaccharide (LPS)-induced ALI by activating SIRT1 remains unclear. Mice underwent intratracheal LPS injection to mimic sepsis-induced ALI while MLE-12 cells were treated with LPS for 6 h to establish an in vitro ALI model. At the same time, mice or MLE-12 cells were treated with different doses of LIG to access its pharmacological effect. The results demonstrated that LIG pretreatment could improve LPS-induced pulmonary dysfunction and pathological injury, apart from increasing 7-day survival rate. In addition, LIG pretreatment also decreased inflammation, oxidative stress and apoptosis during LPS-induced ALI. Mechanically, LPS stimulation decreased the expression and activity of SIRT1 but increased the expression of Notch1 and NICD. And LIG could also enhance the interaction between SIRT1 and NICD, thus deacetylating NICD. In vitro experiments also unveiled that EX-527, a selective SIRT1 inhibitor, could abolish LIG-elicited protection in LPS-treated MLE-12 cells. And in SIRT1 knockout mice with ALI, LIG pretreatment also lost its effects on inflammation, apoptosis, and oxidative stress during ALI.


Role of pulmonary resection in the diagnosis and treatment of limited-stage small cell lung cancer: revision of clinical diagnosis based on findings of resected specimen and its influence on survival.
Our aims were to evaluate (1) the result of surgical treatment of limited-stage small cell lung cancer (SCLC) by examining long-term survival and prognostic factors, (2) the diagnostic role of surgery by comparing clinical and histopathological diagnoses and staging, and (3) the impact of preoperative diagnostic accuracy on survival. We retrospectively reviewed the clinical profiles of 37 patients treated at our institution between January 1990 and December 2007 for SCLC diagnosed using surgical specimens. The median follow-up period was 41.2 months, and the 5-year survival rate was 57.5%. Lobectomy or wider resection was performed alone in 33 cases and with mediastinal dissection in 29 cases. Fifteen patients did not receive chemotherapy. SCLC was diagnosed preoperatively or intraoperatively in 75% and non-SCLC in 25%. Clinical stage 1 disease was diagnosed in 29 patients; however, pathological stage 1 was seen in only 20. Patients at pathological stage 1 disease showed better survival than those at stage 2, but a similar result was not obtained in the case of clinical stage of the disease. Tumor size and nodal stage were the only significant factors influencing survival in a multivariate analysis. The adequacy of preoperative clinical diagnosis of tumor extensiveness, nodal involvement, and clinical stage did not significantly influence survival. Surgery for limited-stage SCLC was associated with a favorable survival rate and provided important pathological information that can help predict survival. Accuracy of preoperative diagnoses showed no apparent impact on survival for surgically treated SCLC patients.


Resource recovery of lignocellulosic biomass waste into lactic acid - Trends to sustain cleaner production.
Biomass waste generation concerns regulatory authorities to develop novel methods to sustain biotransformation processes. Particularly, lactic acid (LA) is a bulk commodity chemical used in diverse industries and holds a growing global market demand. Recently, lignocellulosic waste biomass is preferred for LA bio-production because of its non-edible and inexpensive nature. However, the information about new pretreatment methods for lignocellulosic feedstock, and novel strains capable to produce LA through fermentation is limited. Therefore, this review highlights the advancement of pretreatments methods of lignocellulosic biomass and biotransformation. Herein, we first briefly explored the main sources of lignocellulosic waste biomass, then we explored their latest advances in pretreatment processes particularly supercritical fluid extraction, and microwave-assisted extraction. Approaches for bioconversion were also analyzed, such as consolidated bioprocessing (CBP), simultaneous saccharification and fermentation (SSF), separate hydrolysis fermentation (SHF), among other alternatives. Also, new trends and approaches were documented, such as metagenomics to find novel strains of microorganisms and the use of recombinant strategies for the creation of new strains. Finally, we developed a holistic and sustainable perspective based on novel microbial ecology tools such as next-gen sequencing, bioinformatics, and metagenomics. All these shed light on the needs to culture powerful microbial isolates, co-cultures, and mixed consortia to improve fermentation processes with the aim of optimizing cultures and feedstock pretreatments.


6-(1-alkenoyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinone derivatives:synthesis and evaluation of antitumor activity.
Thirty six 5,8-dimethoxy-1,4-naphthoquinone derivatives, which bear unsaturated alkyl side chain with ester bond, were synthesized and tested cytotoxic activity on L1210 cells and antitumor activity against ICR mice bearing S-180 cells. It could be recognized that the cytotoxicities of naphthoquinones with R1 being methyl and propyl (IV1-24) were not enhanced by replacing the alkanoyls with alkenoyls. In contrast, the introduction of the alkenoyl moieties on the compounds with R1 = hexyl (IV25-36) resulted in the enhancement of their cytotoxicities. Replacement of alkanoyl group with an alkenoyl group generally increased the T/C value of the mice bearing S-180 cells.


ERFVII action and modulation through oxygen-sensing in Arabidopsis thaliana.
Oxygen is a key signalling component of plant biology, and whilst an oxygen-sensing mechanism was previously described in Arabidopsis thaliana, key features of the associated PLANT CYSTEINE OXIDASE (PCO) N-degron pathway and Group VII ETHYLENE RESPONSE FACTOR (ERFVII) transcription factor substrates remain untested or unknown. We demonstrate that ERFVIIs show non-autonomous activation of root hypoxia tolerance and are essential for root development and survival under oxygen limiting conditions in soil. We determine the combined effects of ERFVIIs in controlling gene expression and define genetic and environmental components required for proteasome-dependent oxygen-regulated stability of ERFVIIs through the PCO N-degron pathway. Using a plant extract, unexpected amino-terminal cysteine sulphonic acid oxidation level of ERFVIIs was observed, suggesting a requirement for additional enzymatic activity within the pathway. Our results provide a holistic understanding of the properties, functions and readouts of this oxygen-sensing mechanism defined through its role in modulating ERFVII stability.


"Out of sight, out of mind": housestaff perceptions of quality-limiting factors in discharge care at teaching hospitals.
Improving hospital discharge has become a national priority for teaching hospitals, yet little is known about physician perspectives on factors limiting the quality of discharge care. To describe the discharge process from the perspective of housestaff physicians, and to generate hypotheses about quality-limiting factors and key strategies for improvement. Qualitative study with in-depth, in-person interviews with a diverse sample of 29 internal medicine housestaff, in 2010-2011, at 2 separate internal medicine training programs, including 7 different hospitals. We used the constant comparative method of qualitative analysis to explore the experiences and perceptions of factors affecting the quality of discharge care. We identified 5 unifying themes describing factors perceived to limit the quality of discharge care: (1) competing priorities in the discharge process; (2) inadequate coordination within multidisciplinary discharge teams; (3) lack of standardization in discharge procedures; (4) poor patient and family communication; and (5) lack of postdischarge feedback and clinical responsibility. Quality-limiting factors described by housestaff identified key processes for intervention. Establishment of clear standards for discharge procedures, including interdisciplinary teamwork, patient communication, and postdischarge continuity of care, may improve the quality of discharge care by housestaff at teaching hospitals.


Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia.
Severe congenital neutropenia (SCN) patients treated with CSF3/G-CSF to alleviate neutropenia frequently develop acute myeloid leukemia (AML). A common pattern of leukemic transformation involves the appearance of hematopoietic clones with CSF3 receptor (CSF3R) mutations in the neutropenic phase, followed by mutations in RUNX1 before AML becomes overt. To investigate how the combination of CSF3 therapy and CSF3R and RUNX1 mutations contributes to AML development, we make use of mouse models, SCN-derived induced pluripotent stem cells (iPSCs), and SCN and SCN-AML patient samples. CSF3 provokes a hyper-proliferative state in CSF3R/RUNX1 mutant hematopoietic progenitors but does not cause overt AML. Intriguingly, an additional acquired driver mutation in Cxxc4 causes elevated CXXC4 and reduced TET2 protein levels in murine AML samples. Expression of multiple pro-inflammatory pathways is elevated in mouse AML and human SCN-AML, suggesting that inflammation driven by downregulation of TET2 activity is a critical step in the malignant transformation of SCN.


Identification of differentially accumulated proteins associated with embryogenic and non-embryogenic calli in saffron (Crocus sativus L.).
Somatic embryogenesis (SE) is a complex biological process that occurs under inductive conditions and causes fully differentiated cells to be reprogrammed to an embryo like state. In order to get a better insight about molecular basis of the SE in Crocus sativus L. and to characterize differentially accumulated proteins during the process, a proteomic study based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry has been carried out. We have compared proteome profiles of non-embryogenic and embryogenic calli with native corm explants. Total soluble proteins were phenol-extracted and loaded on 18 cm IPG strips for the first dimension and 11.5% sodium dodecyl sulfate-polyacrylamide gels for the second dimension. Fifty spots with more than 1.5-fold change in abundance were subjected to mass spectrometry analysis for further characterization. Among them 36 proteins could be identified, which are classified into defense and stress response, protein synthesis and processing, carbohydrate and energy metabolism, secondary metabolism, and nitrogen metabolism. Our results showed that diverse cellular and molecular processes were affected during somatic to embryogenic transition. Differential proteomic analysis suggests a key role for ascorbate metabolism during early stage of SE, and points to the possible role of ascorbate-glutathione cycle in establishing somatic embryos.


Electroporation microarray for parallel transfer of small interfering RNA into mammalian cells.
This paper describes the fabrication of microarrays that enable the parallel electroporation of small interfering RNAs (siRNAs) into mammalian cells. To optimize the conditions of microarray preparation and electric pulsing, a self-assembled monolayer was formed on a gold electrode, and a cationic polymer was adsorbed by the entire surface of the monolayer. siRNA was then adsorbed by the cationically modified electrode through electrostatic interactions. Human embryonic kidney cells stably transformed with the expression construct of green fluorescent protein (GFP) were used to examine the electric pulse-triggered transfer of GFP-specific siRNA. A single electric pulse was applied to the cells cultured on the electrode at a field strength of 240 V cm(-1). The expression of GFP was significantly suppressed in a sequence-specific manner two days after pulsing. Microscopic observation and flow-cytometric analysis revealed that the expression of GFP was attenuated in the majority of cells in a loading-dependent manner. Moreover, the effect of siRNA could be temporally controlled by changing the culture periods before pulsing. When a micropatterned self-assembled monolayer was used as a platform for loading siRNA in an array format, gene silencing was spatially restricted to the regions where specific siRNA was loaded. From these results, we conclude that array-based electroporation provides an excellent means of individual transfer of siRNAs into mammalian cells for high-throughput gene function studies.


The INCA® implant to treat isolated scaphotrapeziotrapezoid osteoarthritis: Preliminary results at a minimum 2 years' follow-up.
We report results with the INCA® distal scaphoid pole resurfacing implant anchored within the scaphoid for isolated scaphotrapeziotrapezoid osteoarthritis. Thirty-five implants in 27 patients (mean age, 69 years) were retrospectively included with a minimum follow-up of 2 years. Outcome criteria were pain (VAS), PROMs (QuickDASH, PRWE and MMWS), wrist motion, pinch and grip strength, and radiographic assessment. The average follow-up was 4.6 years. There was a significant improvement in pain, PROMs, grip and pinch strength. Radial deviation and wrist extension showed slight but significant postoperative decrease (-4° for both). Dorsal intercalated segment instability (DISI) was significantly improved postoperatively (7 cases versus 21 preoperatively). There were 2 cases of implant loosening (6%) within the first 10 months: 1 keel malpositioning and 1 insufficient postoperative immobilization. These findings suggest that the INCA® implant is an effective and reliable medium-term solution for isolated scaphotrapeziotrapezoid osteoarthritis. By restoring scaphoid length and gliding on the trapeziotrapezoid surface, the implant contributes to restoring normal bone alignment of the wrist.


Relative reproductive effort in males and females of the dioecious shrub Oemleria cerasiformis.
We derived an index of reproductive effort (g reproductive tissue per g leaf) from data collected over two seasons on 28 males and 28 females of the dioecious shrub Oemleria cerasiformis. Males produced an average of three times as much flower and flower-stalk tissue as females, but because of their large fruits, females produced four times as much total reproductive biomass. Reproductive effort of both sexes was related to light. Fruit set in females (% carpels producing drupes) averaged 11.2% and was related to spring light levels. Male-biased sex ratios in this species may be related to the greater reproductive effort of females.


Immunospecific NMR contrast agents.
Most NMR contrast agents suggested to date have been paramagnetic. These agents, which include the transition and lanthanide metal ions as well as stable organic free radicals, do not provide effective contrast at concentrations much below 1 mM. However, the use of macromolecular ferromagnetic and superparamagnetic particles provides, for the first time, an NMR relaxation agent that is effective at subnanomolar concentrations. Two different sized superparamagnetic particles have been coupled to monoclonal antibodies with high affinity for a neuroblastoma-specific cell surface antigen. The specific binding of these particles, both in vivo and in vitro is demonstrated and the consequences for immunospecific NMR contrast are discussed.


Comprehensive Contact Tracing, Testing and Sequencing Show Limited Transmission of SARS-CoV-2 between Children in Schools in Norway, August 2020 to May 2021.
The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools has been a topic of controversy. In this study among school contacts of SARS-CoV-2 positive children in 43 contact-investigations, we investigated SARS-CoV-2 transmission in Norway, August 2020-May 2021. All participants were tested twice within seven to ten days, using SARS-CoV-2 PCR on home-sampled saliva. Positive samples were whole genome sequenced. Among the 559 child contacts, eight tested positive (1.4%, 95% CI 0.62-2.80), with no significant difference between primary (1.0%, 95% CI 0.27-2.53) and secondary schools (2.6%, 95% CI 0.70-6.39), p = 0.229, nor by viral strain, non-Alpha (1.4%, 95% CI 0.50-2.94) and Alpha variant (B.1.1.7) (1.7%, 95% CI 0.21-5.99), p = 0.665. One adult contact (1/100) tested positive. In 34 index cases, we detected 13 different SARS-CoV-2 Pango lineage variants, with B.1.1.7 being most frequent. In the eight contact-investigations with SARS-CoV-2 positive contacts, four had the same sequence identity as the index, one had no relation, and three were inconclusive. With mitigation measures in place, the spread of SARS-CoV-2 from children in schools is limited. By excluding contact-investigations with adult cases known at the time of enrolment, our data provide a valid estimate on the role of children in the transmission of SARS-CoV-2 in schools.


Modifications in cerebral lipid metabolism by severe glucose deprivation during aging.
Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age.


The presence and longevity of peripherally expanded donor-derived TCRalphabeta+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias.
There are two major pathways for T-cell regeneration after allogeneic bone marrow transplantation; thymus-dependent T-cell differentiation of T-cell progenitors, and peripheral expansion of mature T cells in the graft. In order to learn to what extent the peripheral expansion of donor-derived mature T lymphocytes contributes to reconstitution of the TCRalphabeta+ T-cell repertoire after allogeneic bone marrow transplantation for adult myeloid leukemias, we pursued the fate of donor-derived T-cell clones using the amino-acid sequences of the complementarity-determining region 3 (CDR3) of the TCR-beta chain as a clonal marker. Clonal expansion of TCRalphabeta+ T lymphocytes with specific TCRBV subfamilies was identified in donor blood. Identical T-cell clones were not found in blood from recipients before transplantation. The donor-derived T-cell clones were identified in the circulating blood from recipients a few months after allogeneic bone marrow transplantation, and they remained in the blood for 18 months after transplant in two recipients, and for 56 months in one. These results suggest that the peripheral expansion of mature T lymphocytes in the graft makes a significant contribution to post-transplant T-cell regeneration during the early period of transplantation in humans, and that mature T cells can survive in recipients for several years. Further investigation will be required to explore which antigens drive the expansion of T-cell clones in donors and recipients, and the mechanisms of maintaining homeostatic balance between the thymus-dependent pathway and the peripheral expansion of mature T cells in post-transplant T-cell regeneration.


Agitation and somnolence by bilateral paramedian thalamic infarct.
Bilateral thalamic infarction in paramedian artery territory may present with severe acute illness, confusion, coma and memory impairment. However, subtle clinical presentation as in our case should alert the clinician to consider such a diagnosis as it can be associated with good prognosis. Bilateral thalamic infarct is a rare form of stroke. Mostly thalamic infarcts are unilateral. In most cases, bilateral thalamic infarction leads to cognitive dysfunction, opthalmoparesis, conscious impairment, behavioral disturbance, and corticospinal dysfunction. Here, we describe the case of a 75-year-old male patient who presented to the emergency department of our hospital with agitation and somnolence for one day. He had poorly controlled hypertension. There was no previous history of stroke, diabetes mellitus, hyperlipidemia, known cardiac disease, or smoking history. There was no seizure, recent headache, or visual disturbance. The patient was somnolent and not oriented to time, person, or place. Neurological examination did not show any focal weakness or vertical eye movement restrictions. Other systemic examinations, including those of the respiratory and cardiovascular systems, were unremarkable. Extensive laboratory investigations excluded potential metabolic, infectious, endocrine, or toxic etiologies. The patient did not have any recent history of drug misuse, including benzodiazepines. Brain MRI with diffusion-weighted imaging showed an acute bilateral thalamic infarct. Cerebral angiography was unremarkable. The patient was treated with low molecular weight heparin 60 mg subcutaneously, aspirin 300 mg daily, and haloperidol 5 mg twice daily for agitation. After two weeks of intrahospital treatment, his condition improved (consciousness and orientation massively improved).


The effect of the combination of lithium and haloperidol on brain intermediary metabolism in vivo.
The effect of the chronic administration of the combination of lithium and haloperidol has been studied in rat brain in vivo. Lithium was administered in food in amounts sufficient to maintain serum lithium levels of 1.0 +/- 0.1 mEq/l; haloperidol (1.5 mg/kg) was given i.p. once daily. Control animals pair-fed with the lithium/haloperidol alone, or neither drug. Fifteen days after the beginning of the experiments the brains were instantaneously frozen with a rapid brain-freezing device and multiple metabolites were measured in the perchloric acid extract of the tissue. Intermediates examined included selected metabolites of the glycolytic pathway and the tricarboxylic acid cycle, N-acetylaspartate and cofactors such as ATP, CoA, and acetyl-CoA. Estimates of the effects of the treatments on cytoplasmic and mitochondrial redox states were also made. The results showed only minor effects of any of the treatments on any of the parameters studied and little or nothing to distinguish the combination of lithium and haloperidol from either treatment alone.


Epidemiology of multi-resistant organisms - challenges to a regional data management system.
The health care region Baltic Coast is within the framework of the joint project HICARE (Health, Innovative Care & Regional Economy) to be developed from January 2011 to December 2014 into a model region to combat the spread of multi-resistant organisms (MRO). The concept of the project area "IT & Epidemiology" will be introduced here. An IT system is to be developed and implemented consisting of two interconnected elements, a central data management and a web-based support system for information and decision. Particular challenges are the consolidation of data decentrally collected from numerous and heterogeneous data sources, compliance with the data privacy protection laws and the complex management of patients' informed consent. The information collected by the central data management will be the basis of epidemiological evaluations. Prevalence and incidence of MRO in patients and staff of medical facilities, single risk factors as well as risk profiles, the range and extent of treatments including their effectiveness and sustainability will be investigated. Furthermore, cost and cost-utility analyses will be performed.


Aerobic CuBr2-Catalyzed Oxidative Coupling Reaction of Amidines with Exocyclic α,β-Unsaturated Cycloketones for the Synthesis of Spiroimidazolines.
A CuBr2-catalyzed cascade reaction of amidines with exocyclic α,β-unsaturated cycloketones was developed, affording a large variety of spiroimidazolines in moderate to excellent yields. The reaction process involved the Michael addition and copper(II)-catalyzed aerobic oxidative coupling, in which O2 from air acted as the oxidant and H2O was the sole byproduct.


Reduction in mercury bioavailability to Asian clams (Corbicula fluminea) and changes in bacterial communities in sediments with activated carbon amendment.
Activated carbon (AC) amendment is considered as one of the alternatives for managing and remediating mercury (Hg) contaminated sediments because of its high sorptive capacity and potential to immobilize the contaminant. For this study, the underlying mechanisms that control the reduction of Hg bioavailability in AC-amended estuarine sediments were investigated in box microcosm set-ups with 28-day Asian clam bioassay experiments. The application of diffusive gradients in thin film technique (DGT) revealed that the total mercury and methylmercury levels in sediment pore water decreased by 60%-75% in 1%-3% AC-amended sediments. This decrease subsequently led to a linear reduction in the Hg body burden in Asian clams, even at 1% sorbent mixing. These observations implied that AC amendment reduced the net flux of Hg into the pore water and overlying water, resulting in reduced Hg bioaccumulation in benthic organisms. The addition of AC to sediment also led to reduced dissolved organic carbon and several biogeochemical indicators (HS-, Mn, and Fe) in the pore water. Furthermore, the 16 S rRNA gene amplicon sequencing analysis revealed noticeable alterations in the microbial communities after AC amendment. The predominant phylum was Firmicutes in control sediment, Bacteroidetes in 1% AC-amended sediment, and Proteobacteria in both 2% and 3% AC-amended sediment samples. The genera-level analysis showed that the relative abundance of the Hg-methylators decreased as the level of AC amendment increased. These observations suggested that AC amendment decreased Hg bioavailability not only by physicochemical sorption but also by changing geochemical species and shifting the microbial community composition.


Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route.
To evaluate the effect of intrathecal therapy with human antitetanus immunoglobulin on clinical progression of and mortality from tetanus. Randomised controlled trial. Intensive care unit of a university hospital, Pernambuco, Brazil. 120 patients with tetanus allocated to antitetanus immunoglobulin by either the intrathecal and intramuscular route (n = 58) or the intramuscular route (n = 62; control group). Clinical progression of disease, duration of hospital stay, duration of occurrence of spasms, complications, respiratory infection, respiratory failure or mechanical ventilation, duration of respiratory assistance, and mortality. Patients in the treatment group showed a better clinical progression than those in the control group (chi2 for trend 7.752, P = 0.005; difference in proportion of patients with improvement 20%, 95% confidence interval 4% to 35%). The duration of occurrence of spasms, hospital stay, and respiratory assistance were all shorter in patients the treatment group: respectively, 14.96, 0.0001 (difference in proportion of patients with spasms lasting < or = 10 days 36%, 18% to 55%); 4.56, 0.03; and 6.56, 0.01 (proportion of patients who needed assistance for < or = 10 days 69.2% in the treatment group and 30.8% in the control group (difference 38%, 12% to 65%)). Patients treated with antitetanus immunoglobulin by the intrathecal route show better clinical progression than those treated by the intramuscular route.


Behavioral modification in a weight-reduction program.
Previous surveys have shown a high prevalence of obesity in women of low socioeconomic status. This study confirmed the relationship in the Medical Appointment Clinic at Grady Memorial Hospital, Atlanta. Behavioral modification therapy for obesity had not been carefully tested in this type of population. Therefore, a behavioral modification group-oriented weight-reduction method was adapted for 80 participants from this setting. Eighty controls, matched for age, sex, race, and percent ideal body weight, received individualized counseling from a dietitian. Thirty-one matched pairs (62 individuals) had follow-up weights taken more than one year later. Thirteen percent (four) of the behavioral modification group participants versus 6.4% (two) of the control participants maintained a loss of 20 lb. or more during this period. The mean weight loss for the behavioral modification group was 4.6% of their ideal body weight versus 0.9% for the control group. The results of the behavioral modification program were statistically superior to those of the control program (p = 0.058). Overall, for participants whose mean weight was 241 lb., it is difficult to conclude that a mean 5-lb. weight loss represents a meaningful change or that this weight loss was due to behavioral modification. The results of this program among low socioeconomic status women, however, were comparable with the results of similar large, free-living programs among middle class participants.


Anti-inflammatory activity of telmisartan in rat models of experimentally-induced chronic inflammation: Comparative study with dexamethasone.
Recently, significant progress has been made through the application of peroxisome proliferator activated receptor-γ (PPAR-γ) agonists as anti-inflammatory drugs that are efficacious, relatively free of side effects, and can be used effectively for a long time. The present study was designed to evaluate the dose-response relationship of the anti-inflammatory activity of telmisartan in rat models of chronic inflammation. The study protocol includes four stages: First stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of different doses of telmisartan in rat model of formaldehyde-induced chronic inflammation. Second stage: six rats were used to study the anti-inflammatory activity of telmisartan (1.5 mg/kg) in combination with dexamethasone (0.5 mg/kg) in the same model. Third stage: 48 rats were allocated into eight groups, each containing six rats, for the study of the anti-inflammatory activity of telmisartan in rat model of cotton pellet-induced granuloma. Fourth stage: six rats were used to study the anti-inflammatory activity of telmisartan (1.5 mg/kg) when used as adjuvant with dexamethasone (0.5 mg/kg) in the same model. Telmisartan in a dose-dependent pattern (0.1, 0.2. 0.4, 0.6, 1.5, 3 mg/kg) significantly suppressed inflammation in rat models of formaldehyde-induced chronic inflammation and cotton pellet-induced granuloma. When combined with dexamethasone, telmisartan (1.5 mg/kg body weight) significantly suppressed inflammation in both models, which is significantly higher than all of the effects produced by other approaches of treatment when telmisartan used alone. In conclusion, telmisartan decreased formaldehyde-induced chronic inflammation and cotton-pellet induced granuloma in rats in a dose-dependent pattern. Therefore, it may be considered as a potential treatment for chronic inflammatory conditions in human.


The effect on ozone catalytic performance of prepared-FeOOH by different precursors.
In this study, different precursors were used to prepare FeOOH and the ozonation catalytic activity was s investigate by using ibuprofen as the degradation substrate. It could be found that FeOOH prepared from ferric sulfate performed higher activity. Subsequently, the catalysts were characterized by X-ray diffraction, Fourier transform infrared spectrometer, scanning electron microscope and N2 adsorption-desorption techniques. X-ray diffraction and Fourier transform infrared spectrometer showed that the synthesized FeOOH consisted of α-FeOOH and β-FeOOH mainly. Scanning electron microscope showed that their appearance and morphology were significantly different, and the FeOOH prepared from ferric sulfate had a larger specific surface area, resulting in its better catalytic activity. Finally, the hydroxyl groups and pHzpc of the catalyst surface were measured. It was also found that the FeOOH prepared from ferric sulfate owned more hydroxyl groups and the pHzpc of the surface was closer to the pH of the degradation substrate, which illustrated the reasons for the increased catalytic activity. In addition, the degradation kinetics conformed to the pseudo first-order kinetic model and the hydroxyl radicals played an important role in the reaction process.


The influence of ethnicity and glucose tolerance status on subjective hunger sensations and prospective food intake in overweight and obese Asian and European Australians.
To examine the influence of ethnicity and glucose tolerance status on subjective sensations and food intake in overweight/obese Asian and European Australians. 18 Asians and 26 Europids were classified as normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) based on serial measures of finger-prick glucose following an oral glucose tolerance test (OGTT). Subjective sensations of hunger and satiety were measured before and every 15min after the OGTT using a visual analogue scale (VAS). Food intake was measured covertly from consumption of a buffet style lunch and from self-maintained 24h food records. All serial measurements were converted into total area under the curve (TAUC) and comparisons adjusted for age, fat and fat-free mass. There was a significant difference interaction between ethnicity (ETH) and glucose tolerance (GTT) for subjective fullness, desire for food and prospective food intake. IGT Asians had significantly greater sensations of fullness, but lesser prospective food and desire to eat, as compared to other groups. However there were no differences in calorie and macronutrient intake at buffet lunch or over 24-h. Interactions between ethnicity and glucose tolerance status in subjective sensations did not transcribe to differences in prospective food intake.


Relative immunogenicity of blood group antigens: First report in a Korean population.
The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population. All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units. A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E > c > e > C > K > Jk(a) > Lu(a) > S > Fy(a) > Fy(b) > Jk(b) > Di(b) > Di(a) in the total population and E > c > e > C > Jk(a) > Fy(a) > Fy(b) > S > K > Lu(a) > Jk(b) > Di(b) > Di(a) in male patients. The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions.


Effect of terminated fetal circulation on maternal angiogenic factors in severe early preeclampsia.
BACKGROUND; Although intrauterine presence of the placenta is essential in the etiology of preeclampsia (PE), case reports showed that the viability of the fetus influences the clinical course of PE and the intensity of the clinical symptoms. We examined the course of angiogenic factors soluble fms-like tyrosine kinase-1 receptors (sFlt-1) and placental growth factor (PlGF) in a case of severe early PE in week 22 + 1 of gestation, when fetal termination was required to stabilize maternal condition. The cessation of the feto-placental perfusion via fetocide led to a reduction of the maternal sFlt-1 concentration of 8.3% which was associated with a decline of the sFlt-1/PlGF ratio from 405 to 334. Nevertheless, the highest change of the angiogenic factors was detected after ejection of the fetus and placenta. Our observations implicate that neither a vital fetus nor an intact feto-placental component is an obligatory prerequisite for the angiogenic imbalance that is associated with the preeclamptic phenotype.


[Evaluation of venous hemodynamics as the decisive diagnostic criterion for venous surgery].
The different physical screening tests (ultrasound Doppler technique, plethysmography, phlebodynamometry) are easy documented and make possible a less dangerous, less expensive, and extensive statement about the venous hemodynamics of the lower extremity. The quota of diagnostic error can be minimized and the indication for operation is secure.


Formation of natural biofilms during chlorine dioxide and u.v. disinfection in a public drinking water distribution system.
The influence of two disinfection techniques on natural biofilm development during drinking water treatment and subsequent distribution is compared with regard to the supply of a high-quality drinking water. The growth of biofilms was studied using the biofilm device technique in a real public technical drinking water asset. Different pipe materials which are commonly used in drinking water facilities (hardened polyethylene, polyvinyl chloride, steel and copper) were used as substrates for biofilm formation. Apart from young biofilms, several months old biofilms were compared in terms of material dependence, biomass and physiological state. Vital staining of biofilms with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and the DNA-specific 4',6-diamidino-2-phenylindole (DAPI) staining resulted in a significant difference in physiological behaviour of biofilm populations depending on the disinfection technique. Compared with chlorine dioxide disinfection (0.12-0.16 mg l-1), the respiratory activities of the micro-organisms were increased on all materials during u.v. disinfection (u.v.254; 400 J m-2). The biofilm biocoenosis was analysed by in situ hybridization with labelled oligonucleotides specific for some subclasses of Proteobacteria. Using PCR and additional hybridization techniques, the biofilms were also tested for the presence of Legionella spp., atypical mycobacteria and enterococci. The results of the molecular-biological experiments in combination with cultivation tests showed that enterococci were able to pass the u.v. disinfection barrier and persist in biofilms of the distribution system, but not after chlorine dioxide disinfection. The results indicated that bacteria are able to regenerate and proliferate more effectively after u.v. irradiation at the waterworks, and chlorine dioxide disinfection appears to be more applicative to maintain a biological stable drinking water. As far as the application of u.v. disinfection is used for conditioning of critical water sources for drinking water, the efficiency of u.v. irradiation in natural systems should reach a high standard to avoid adverse impacts on human health.


Adsorption and desorption behaviors of cesium on rayon fibers coated with chitosan immobilized with Prussian blue.
Rayon fiber coated with chitosan (CTS) that contained immobilized Prussian blue (KFe) (KFe/CTS/rayon) were investigated for the removal of cesium ion (Cs+) from contaminated water. The morphology and mechanical strength of the fibers were observed using scanning electron microscopy (SEM) and a universal testing machine, respectively. The Cs+ concentration was determined by inductively coupled plasma-atomic emission spectroscopy. SEM images revealed that the surface of the KFe/CTS/rayon fiber showed the most roughness. It was found that Cs+ was absorbed from the water by the KFe on the fibers in a molar ratio of 1:1 (Cs+:KFe). After treating the KFe/CTS/rayon fiber with 1% HNO3 for 3h, 48.8% Cs+ desorption was observed. Woven fibers were interlaced with either 2 or 4 lines of the KFe/CTS/rayon fiber from 16 bobbins. The tensile strengths of those fibers were 19.06 and 14.25MPa, respectively. When silver cotton was used as the core axis of the woven fiber, the tensile strength of the fibers interlaced with 2 and 4 lines increased to 27.18 and 25.17MPa, respectively. Moreover, the results of hot tests using radioactive Cs+ showed that the woven KFe/CTS/rayon fibers could absorb up to 1000Bqg-1 from an initial concentration of 8000Bqkg-1.


Effects of fluoxetine administration on mu-opoid receptor immunostaining in the rat forebrain.
Fluoxetine is a selective serotonin reuptake inhibitor. Analysis of mu-opioid receptor immunostaining after chronic fluoxetine administration in rats revealed an increase in the density of cells expressing mu-opioid receptors in the caudatus-putamen, the dentate gyrus, the lateral septum and the frontal, parietal and piriform cortices. These data suggest that mu-opioid receptor expression in the rat forebrain is altered by in vivo chronic fluoxetine treatment.


Smoking affects collagen synthesis and extracellular matrix turnover in human skin.
Smoking is associated with premature facial wrinkling and aberrant wound healing, but the underlying mechanisms of skin injury are poorly understood. To compare the in vivo collagen synthesis and degradation in the skin of smokers and non-smokers. The study population consisted of 47 current smokers and 51 individuals who had never smoked from northern Finland. Suction blisters were induced in the sun-protected upper inner arm of the study subjects, after which suction blister fluid (SBF) was collected for analyses of the levels of aminoterminal procollagen propeptides of type I and III collagens (PINP and PIIINP, respectively), matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP (TIMP)-1. PINP, PIIINP and TIMP-1 were also determined from serum samples. The levels of active and pro MMP-1 were assessed from deep-frozen skin biopsies by Western blotting. The synthesis rates of type I and III collagens were lower by 18% and 22%, respectively, in the SBF of the smokers compared with the non-smokers. The levels of MMP-8 were higher by 100% in the SBF of the smokers. The levels of MMP-1 in the skin biopsies did not differ significantly between the groups. The levels of TIMP-1 in SBF were 14% lower in the smokers than in the non-smokers, whereas the serum concentrations of TIMP-1 did not differ between the groups. Smoking decreases the synthesis rates of type I and III collagens in skin in vivo and alters the balance of extracellular matrix turnover in skin.


USP7-mediated JUND suppresses RCAN2 transcription and elevates NFATC1 to enhance stem cell property in colorectal cancer.
Cancer stem cells (CSCs) encompass a subset of highly aggressive tumor cells that are involved in tumor initiation and progression. This study investigates the function of regulator of calcineurin 2 (RCAN2) in the stem cell property in colorectal cancer (CRC). By analyzing four GEO datasets, we obtained RCAN2 as a stemness-related gene in CRC. RCAN2 was poorly expressed in CRC tissues and cells, especially in CSCs. RCAN2 restoration reduced calcineurin activity and promoted phosphorylation and degradation of nuclear factor of activated T cells 1 (NFATC1) protein, leading to reduced stemness of CSCs. JunD proto-oncogene (JUND), whose protein level was increased in CRC samples and CRC stem cells, bound to RCAN2 and suppressed its transcription. The abundant ubiquitin specific peptidase 7 (USP7) in CSCs enhanced JUND protein stability through deubiquitination modification. Lentivirus-mediated knockdown of USP7 or JUND also blocked the calcineurin-NFATC1 signaling and reduced the protein levels of stemness-related proteins. Moreover, the USP7 knockdown weakened the colony/sphere formation ability as well as the tumorigenicity of CSCs, and it reduced the CSC content in xenograft tumors. However, further restoration of JUND rescued the stemness of the CSCs. Overall, this study demonstrates that USP7-mediated JUND suppresses RCAN2 transcription and activates NFATC1 to enhance stem cell property in CRC. 1. RCAN2 is poorly expressed in CRC tissues and cells and especially in CSCs. 2. RCAN2 reduces stemness of CSCs by blocking calcineurin-NFATC1 signal transduction. 3. JUND binds to RCAN2 promoter to suppresses RCAN2 transcription. 4. USP7 enhances JUND protein stability via deubiquitination modification. 5. Downregulation of USP7 or JUND restores RCAN2 level and suppresses stemness of CSCs.


Beyond the Impact Factor: Reflecting on Twenty Years of Leading Efforts in Research, Innovation in Publishing, and Investment in People.
This viewpoint celebrates the accomplishments of the Journal of Medical Internet Research on its twentieth anniversary and reviews accomplishments around research publications, journal innovation, and supporting people.


Membrane-bound base-exchange reactions in animal tissues.
The calcium-stimulated incorporation of ethanolamine, L-serine and choline into rabbit synaptosomal phospholipids in vitro has been investigated. The synaptosomal membranes were prelabelled in vitro in their choline-, ethanolamine- or serine-phosphoglycerides by base-exchange and then chasing experiments were performed by displacing the lipid-bound base by ethanolamine, choline or L-serine labelled with a different isotope. The results indicate that membrane phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are substrates for the exchange with all the three mentioned bases. A very small phospholipid pool (0.5-2% of the total available pool) is active in the calcium-dependent exchange between membrane phosphatidylcholine or phosphatidylethanolamine and free bases, whereas the pool of exchanging phosphatidylserine is sensibly larger (2-9%). In another series of experiments the effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. An exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects. The possible physiological importance of phospholipid pool at the synaptosomal level is discussed.


Association between time-related changes in routine blood morphological parameters and renal function after transcatheter aortic valve implantation - a preliminary study.
Transcatheter aortic valve implantation (TAVI) although minimally invasive is still accompanied by changes in blood morphological parameters, some of them linked to unfavorable outcomes. To find any association between changes in blood morphology reflecting an inflammatory response and acute kidney injury (AKI). This study involved 176 consecutive transfemoral TAVI patients with a mean age of 78.4 ±7.0 years. Serum creatinine concentration (CREA) and blood morphology were analyzed in the blood samples taken before the procedure, then approximately 1, 24, 48 and 72 hours after the procedure, and lastly at the time of discharge. Post-procedural maximal or minimal values (max/min) and max/min-to-bs ratio of the laboratory parameters were also calculated. Leucocyte (WBC) and neutrophil (NEUT) counts increased significantly after the procedure whereas lymphocyte (LYMPH) counts declined markedly, reaching the highest or lowest values 24 hours after the procedure. A significant increase in neutrophil-to-lymphocyte ratio (NLR) was observed. Platelet count (PLT) dropped to a minimum at 72 hours after TAVI but at discharge did not return to the admission level. TAVI was associated with a marked increase in CREA with a peak at 48 hours after the procedure (135.7 ±75.9 μM/l). Patients with AKI (n = 65; 36.9%) presented more pronounced variations in relative changes in counts of all blood morphological parameters. A positive moderate (r = 0.412) correlation between maximal NLR and relative CREA changes was noted. TAVI is associated with significant changes in blood morphological parameters that reflect an inflammatory response. They are more pronounced among subjects with post-procedural AKI.


Sternal fixation with resorbable suture material.
The applicability of absorbable sutures for sternal closure was investigated. Heavy braided Polydioxanon (PDS Ethicon) sutures were tested in a routine fashion, as were steel wire and braided polyester. In a pilot study, 2 patients (20%) had a complete sternal dehiscence. These results forced us to abandon the project.


Postural equilibrium during pregnancy: decreased stability with an increased reliance on visual cues.
The purpose of this study was to determine whether there are changes in postural equilibrium during pregnancy and to examine whether the incidence of falls increases during pregnancy. Static postural balance measures were collected from 12 pregnant women at 11 to 14, 19 to 22, and 36 to 39 weeks gestation and at 6 to 8 weeks after delivery and from 12 nulligravid control subjects who were matched for age, height, weight, and body mass index. Subjects were asked to stand quietly on a stable force platform for 30 seconds with eyes open and closed. Path length and average radial displacement were computed on the basis of the average of 3 trials for each condition. The women were asked at each session if they had sustained a fall in the previous 3 months. Postural stability remained relatively stable during the first trimester; however, second and third trimester and postpartum values for path length and average radial displacement with eyes open and closed were increased significantly compared with the control subjects, which indicates diminished postural balance. The difference between the eyes open and closed values of path length increased as pregnancy progressed. Although 25% of pregnant women sustained falls, none of the control subjects had fallen in the past year. These data suggest that postural stability declines during pregnancy and remains diminished at 6 to 8 weeks after delivery. The study also indicates that there is an increased reliance on visual cues to maintain balance during pregnancy.


Clinical manifestations and consequences of influenza.
The spread of influenza virus through a community typically causes large increases in medical visits for febrile respiratory disease. Increased school absenteeism occurs early in the epidemic, and school children appear to be important for disseminating the virus. Industrial absenteeism, hospitalizations of adults and infants for pneumonia, and deaths due to pneumonia-influenza all tend to peak later in the epidemic. Although influenza infection rates are highest in persons of school age, hospitalizations and deaths occur primarily in infants and in the elderly, particularly among those with pulmonary, cardiovascular, or other debilitating disorders. Influenza viruses can be spread by aerosol or contact. The primary target cells are those of the respiratory epithelium. In healthy adults, the typical influenza syndrome includes fever, cough, and general aches for three to seven days, but lassitude, cough, and evidence of small-airways disease may persist for weeks. Laryngotracheobronchitis, pneumonia, and unexplained fever are prominent manifestations of influenza that lead to hospitalization of young children. Adults are more likely to have complications of bacterial pneumonia and worsening of chronic pulmonary disease or congestive heart failure. Less frequent complications include myositis, various neurologic disorders, and Reye's syndrome. These consequences of influenza clearly justify strenuous efforts at prevention and control.


Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.
The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them. We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment. Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options. No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.


Gastrointestinal trichostrongylosis can predispose ewes to clinical mastitis after experimental mammary infection.
Objective was to study, in an experimental model, the possible role of gastrointestinal nematode infection in predisposing ewes to mastitis during the lactation period. Twenty-four ewes (A or B [n=12]), free from nematode and trematode helminths, were used. Group A animals received 5000 third-stage larvae of a trichostrongylid helminth cocktail and group B ewes were unparasitised controls. Animals in group A developed gastrointestinal trichostrongylosis confirmed by >500epg in faecal samples; mean epg of group B ewes were <20 (P<0.001). Ewes were challenged by deposition of Mannheimia haemolytica into the teat duct. In group A, 7 ewes developed clinical and 5 subclinical mastitis; no ewe in group B developed clinical mastitis, but only subclinical (12 ewes) (P=0.002). M. haemolytica was isolated from 132/132 and 121/132 udder samples from group A or B, respectively (P<0.015); increased leucocyte numbers were recorded in 66/66 and 61/66 samples, respectively (P=0.023). During post-mortem examination, mean number of helminths in gastrointestinal content was 2523 and 7.5 in group A or B, respectively (P<0.001); within group A, proportions of Teladorsagia and Haemonchus were significantly greater in ewes that developed clinical mastitis than in others which did not (0.709 and 0.162 versus 0.662 and 0.136, respectively; P<0.035). M. haemolytica was isolated from 36/36 and 19/36 udder tissue samples from group A or B, respectively (P<0.001). In ewes with subclinical mastitis (in group A or B), inducible-lymphoid-follicles were observed in the teat, which were not observed in ewes with clinical disease. Total pathology scores summed over all days were 127 and 73 for group A or B ewes, respectively (maximum possible 192; P<0.05). In general, there was positive correlation between intestinal helminth counts and pathology score (P<0.001) and between Teladorsagia counts and pathology score (P=0.002) in ewes that developed clinical mastitis. It is concluded that, in view of bacterial challenge, gastrointestinal trichostrongylosis and particularly Teladorsagia infection, might lead to clinical mastitis, through various pathogenetic pathways.


Complete intron/exon organization of DNA encoding the alpha' chain of human C3.
The third component of human complement (C3), a central molecule in both the classical and alternative pathways of complement, is comprised of two polypeptides, termed the alpha and beta chains. Activation of C3 cleaves the alpha chain into two fragments, C3a, an inflammatory peptide, and the alpha' chain which remains covalently linked to the beta chain. Proteolytic fragments derived from the alpha' chain during activation and regulation of complement play a significant role in host defense and regulation of the immune response. Two cosmid clones covering the alpha' chain region were used to characterize the structure of this portion of the C3 gene. The alpha' chain is encoded by 24 exons, which range in size from 52 to 213 base pairs (bp) with an average size of 115 bp. The splice donor sequence at the beginning of intron 12 has a rare sequence variant of GC instead of the usual GT sequence. Ten introns have been completely sequenced and were surprisingly short, ranging in size from 85 to 242 bp with an average of 140 bp. Other introns range in size from 250 bp to over 4 kilobases in length. The gene size for this portion of C3 is estimated to be 23-24 kilobases. Comparison of exon structure with protein domains and with peptide mapping studies demonstrates that several binding sites on C3 are encoded by single exons. These data support the hypothesis that individual exons can code for functional protein domains.


Silver nanoparticles induce lysosomal-autophagic defects and decreased expression of transcription factor EB in A549 human lung adenocarcinoma cells.
Although silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary damage is unclear. AgNPs are incorporated into cells and processed via the autophagy pathway. We examined the effects of AgNP exposure on autophagic flux and expression of transcription factor EB (TFEB) in A549 lung adenocarcinoma cells. In cells exposed to citrate-coated 60-nm AgNPs, confocal laser microscopic examination showed a decrease in the LysoTracker fluorescence signal and an increase in that of Cyto-ID, indicating lysosomal pH alkalization and autophagosome formation, respectively. The proteins p62 and microtubule-associated protein light chain 3B-II (LC3B-II) are both degraded by autophagy, and their levels increased depending on AgNP dose. Furthermore, AgNP-induced increase in LC3B-II was not enhanced by treatment with the autophagic inhibitor bafilomycin A1. TFEB mRNA levels, and protein levels in cytosolic and nuclear fractions, were suppressed by exposure to AgNPs, suggesting transcriptional inhibition of TFEB expression. Overexpression of TFEB did not suppress AgNP-induced LC3B-II accumulation and cellular damage, indicating that impairment of autophagic flux and cellular damage by AgNPs might not be primarily caused by reduced TFEB expression. The present study suggests that AgNP-induced lysosomal dysfunction plays a principal role in the autophagic flux defect.


Number of succussion strokes affects effectiveness of ultra-high-diluted arsenic on in vitro wheat germination and polycrystalline structures obtained by droplet evaporation method.
The aim of this study is to investigate whether the number of succussion strokes applied after each dilution step when preparing the homeopathic treatments influences the effectiveness of ultra-high-diluted (UHD) arsenic trioxide at the 45th decimal dilution/dynamization (As2O3 45x). Wheat seeds, previously stressed with ponderal As2O3, were treated with: As2O3 45x, H2O 45x (dynamized control), or pure water (negative control). The succussion was done manually, and various succussion durations (numbers of strokes) were tested for each treatment. Treatment effectiveness was tested blind using the in vitro germination test and the droplet evaporation method (DEM). Data were processed by the Poisson test (germination test) and by two-way analysis of variance (DEM). We evaluated both the in vitro germination rate, by counting the non-germinated seeds, and the complexity of polycrystalline structures (PCS) (local connected fractal dimension (LCFD)) obtained by evaporating leakage droplets from stressed seeds that had been watered with the different treatments. We observed a highly significant increase in germination rate when the number of strokes (NS) was ≥32 for both As2O3 45x and H2O 45x, and a significant increase in the LCFD of PCS for As2O3 45x when the NS was ≥32 and for H2O 45x when it was 70. Both experimental approaches showed increased effectiveness for treatments prepared with a higher number of succussion strokes. These results indicate that succussion may have an important influence on treatment effectiveness, and so highlight the need for further research.


Single neuron activity in the Drosophila larval CNS detected with calcium indicators.
Although the Drosophila larva has been extensively used for genetic studies of synaptic transmission and locomotion, neurophysiological studies have lagged because it is difficult to investigate circuitry and synaptic function in the larval central nervous system (CNS). Here we introduce an optical technique to monitor neuronal activity in the intact Drosophila larval CNS. We loaded neurons retrogradely through cut axons with dextran-conjugated calcium indicators. Fluorescence responses to changes in the concentration of intracellular calcium are sufficiently fast and large to monitor electrical activity in single neurons. Responses to action potentials were detected in motor neuron cell bodies, axons, neurites, dendrites and sensory neuron afferents identified by genetically targeted green fluorescent protein expression. Our findings provide an experimental procedure for testing synaptic function and connectivity within the intact larval CNS.


Factors that enhance rates of completion: what makes students stay?
This study was one of four projects commissioned by NHS London to examine the readiness for work of nurses upon completion of their pre-registration programmes. The study examined the factors that contribute to students completing their nursing programmes. The objectives of the study were to explore understanding the factors that influence the attrition and completion rates of year 2 students on the adult field of a pre-registration nursing programme. An ethnographic case study methodology was employed in two large London NHS Acute trust hospitals, both partnered with the same Higher Education Institution. Data was collected between 2010 and 2011 through a combination of document review, non-participant observation in practice settings, focus groups and interviews A self-selected group of 50 year 2 student nurses from a total population of 200 participated in this study. All students were from the same cohort group at one London-based university who undertook practice learning experiences at two NHS Acute Trust hospitals. The study found a number of factors that impacted on retention which included student identify and the organisation, fostering resilience and clinical support. In addition the Higher Education Institute does not appear to be the most significant factor in a student's decision to continue on the programme, but that practice placement mentors and clinical placements have the greatest impact on student retention. The study is important in that its findings contradict much of the literature on student nurse attrition and retention in that the clinical placement experiences emerges as the most important factor in whether a student chooses to stay or leave the course.


Fine mapping qKRN5.04 provides a functional gene negatively regulating maize kernel row number.
Zm00001d016075 was identified by fine mapping qKRN5.04. The function of Zm00001d016075, negatively modulating maize (Zea Mays L.) kernel row number (KRN), was verified by CRISPR-Cas9. InDel308 located in the promoter of Zm00001d016075 has potential for use as a molecular marker to identify KRN in maize breeding. Kernel row number (KRN), controlled by multiple quantitative trait loci (QTLs), is one of the most important traits that relate to maize production and domestication. Here, fine mapping was conducted to study a major QTL, qKRN5.04, to a 65-kb genomic region using a progeny test strategy in an advanced backcross population, in which Nong531 (N531) and the inbred line of Silunuo (SLN) were employed as the recurrent and the donor parent, respectively. Within this region, there was only one gene (Zm00001d016075) based on the B73 reference genome. Furthermore, we performed regional association mapping using a panel of 236 diverse inbred lines and observed that all significant SNPs were located within Zm00001d016075. The expression of Zm00001d016075 was significantly higher in N531 and qKRN5.04N531 than qKRN5.04SLN, resulting from the different promoter activity of Zm00001d016075. Sequence analysis revealed that InDel308, located in the promoter of Zm00001d016075, was related to the KRN variation in different maize inbred lines. Using the CRISPR-Cas9 strategy, we determined Zm00001d016075 played a role in negatively regulating KRN and had a moderate effect on 10-kernel width, 100-kernel weight, kernels per ear, and grain yield per ear. These results provide critical insights on the genetic basis and quantitative variation for KRN.


Immunohistochemical expression of metallothionein in pleomorphic adenoma of minor salivary glands: a role in the control of apoptosis?
Pleomorphic adenoma is the most common benign neoplasm of both the major and minor salivary glands. The histological features are diverse and are characterized by the involvement of epithelial-myoepithelial structures. Metallothionein is a cysteine-rich protein present in myoepithelial cells of several benign and malignant neoplasms. The function of metallothionein is associated with DNA protection, oxidative stress and apoptosis. The purpose of this study was to evaluate the expression of metallothionein in pleomorphic adenoma of the minor salivary glands. Additionally, we investigated the association of the clinicopathological features of the lesions with metallothionein, specifically its association with Bcl-2, in an attempt to evaluate the role of metallothionein in the control of apoptosis. Thirty-five cases of pleomorphic adenoma were selected and immunohistochemistry was performed for metallothionein and Bcl-2 proteins. The proteins were quantified by the Quickscore method. The samples showed epidemiological characteristics similar to those described in the literature. We did not find an association between the clinicopathological characteristics of pleomorphic adenomas and the proteins studied, but an association between metallothionein and Bcl-2 was demonstrated. The results suggest that metallothionein may have a role in the control of apoptosis in pleomorphic adenoma.


Population differentiation within Festuca rubra L. with regard to soil salinity and soil water.
Seed and transplanted adult plants from populations of Festuca rubra, collected from inland, salt-marsh and sand-dune sites were grown on culture solution with added sodium chloride. The growth of the populations of the three habitats was reduced differentially by salt. The salt marsh ecotype Festuca rubra ssp. litoralis was only slightly affected and the inland ecotype F. rubra ssp. rubra was severely retarded at 60 mM NaCl. The dune ecotype F. rubra ssp. arenaria had an intermediate tolerance. The tolerant ecotypes accumulated less sodium chloride as compared to the sensitive ecotype, suggesting that salt tolerance is caused in part by salt exclusion.In addition, the dune ecotype F.r. arenaria appeared to be more drought tolerant than the salt marsh ecotype. Abscission of salt-saturated leaves does not function as an adaptation to salinity in Festuca rubra.All three ecotypes accumulated proline with increased salinity. The response was most pronounced in the drought tolerant F.r. arenaria, indicating that proline accumulation is a response to osmotic stress rather than to ion-specific effects of salinity. The observed differences in salt tolerance may be explained by differential sensitivity to toxic effects of sodium chloride.The occurrence on a beach plain of closely adjacent populations of F.r. arenaria and F.r. litoralis, differing markedly in salt tolerance, is briefly discussed.


Purification of pyrethrins from flowers of Chrysanthemum cineraraeflium by high-speed counter-current chromatography based on coordination reaction with silver nitrate.
Pyrethrum extract is a natural insecticide that has been used worldwide for centuries, with pyrethrins being considered active ingredients. Their purification is difficult due to their chemical structural similarity and instability to light. In the present study, a coordination complex high-speed counter-current chromatography was used to separate pyrethrins from pyrethrum extract. The two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (10:2:10:2, v/v/v/v) with 0.30 mol/L silver nitrate was selected for separation. As a result, five pyrethrins including cinerin II (31.2 mg), pyrethrin II (43.9 mg), jasmalin II (39.1 mg), pyrethrin I (32.4 mg), and jasmalin I (16.0 mg) were obtained from 400 mg crude extract in 6 h by one-step HSCCC separation, with purities over 95%. The isolated compounds were identified by MS, 1H-NMR and 13C-NMR spectroscopy. The results demonstrated that the addition of silver nitrate in the two-phase solvent system of HSCCC significantly increased the HSCCC separation factor of pyrethrins. HSCCC is a rapid method for purification of pyrenthrins from pyrethrum extract. The established method may also be applied to separate analogous compounds from natural products in which the chemical structure differs in the position or numbers of alkenes.


The construction and operational models of internet hospitals in China: a hospital-based survey study.
China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China. Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals' services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals. Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services (P = 0.006), numbers of doctors outside of the entity (P = 0.006), numbers of online nurses (P = 0.004), and the ratio of online nurses to offline doctors (P < 0.001). Of the 16 aspects evaluated with regards to the medical staff's self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time. While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.


Construction and validation of a reproductive behavior questionnaire for female patients with rheumatic diseases.
Active autoimmune rheumatic diseases (ARDs) before conception increase the risk of flares and adverse pregnancy outcomes. We aimed to construct and validate a reproductive behavior questionnaire in Spanish for patients with ARDs to assess their knowledge and their reproductive behavior. We constructed and validated a reproductive behavior questionnaire in two phases: (1) a literature review followed by interviews of reproductive-age female patients, and (2) a cross-sectional study to complete validation. Convenience sampling was carried out with 165 female patients: 65 participated in the cross-cultural adaptation phase and 100 in the validation phase. The internal consistency was evaluated by estimating Cronbach's alpha and tetrachoric correlation coefficients. Values ≥ 0.40 were considered acceptable (p < 0.05). The initial instrument included 38 questions. Thematic analysis identified 8 important dimensions or topics, which were combined to create the Rheuma Reproductive Behavior interview questionnaire. A final total of 41 items across 10 dimensions were obtained. The test-retest analysis showed perfect correlations in 34 of the 41 items, moderate in 6 items, and negative in one of the items. The mean age of the patients was 35.65 years (SD 9.02), and the mean time to answer the survey was 13.66 min (SD 7.1). The Rheuma Reproductive Behavior questionnaire showed good reliability and consistency capturing patients' reproductive health knowledge and reproductive behavior. Key Points • We designed and validated a questionnaire to assess reproductive health knowledge and reproductive behavior among female patients with ARDs. • The questionnaire was comprehensible for participants, and showed good reliability and consistency capturing reproductive knowledge and behavior. • This tool may aid in the design of strategies to improve reproductive decision-making for female patients with ARDs.


Adaptation to chronic MG132 reduces oxidative toxicity by a CuZnSOD-dependent mechanism.
To study whether and how cells adapt to chronic cellular stress, we exposed PC12 cells to the proteasome inhibitor MG132 (0.1 microM) for 2 weeks and longer. This treatment reduced chymotrypsin-like proteasome activity by 47% and was associated with protection against both 6-hydroxydopamine (6-OHDA; 100 microM) and higher dose MG132 (40 microM). Protection developed slowly over the course of the first 2 weeks of exposure and was chronic thereafter. There was no change in total GSH levels after MG132. Buthionine sulfoximine (100 microM) reduced GSH levels by 60%, but exacerbated 6-OHDA toxicity to the same extent in both MG132-treated and control cells and failed to reduce MG132-induced protection. Chronic MG132 resulted in elevated antioxidant proteins CuZn superoxide dismutase (SOD; +55%), MnSOD (+21%), and catalase (+15%), as well as chaperone heat-shock protein 70 (+42%). Examination of SOD enzyme activity revealed higher levels of CuZnSOD (+40%), with no change in MnSOD. We further assessed the mechanism of protection by reducing CuZnSOD levels with two independent siRNA sequences, both of which successfully attenuated protection against 6-OHDA. Previous reports suggested that artificial over-expression of CuZnSOD in dopaminergic cells is protective. Our data complement such observations, revealing that dopaminergic cells are also able to use endogenous CuZnSOD in self-defensive adaptations to chronic stress, and that they can even do so in the face of extensive GSH loss.


Hemolytic anemia after placement of an intraluminal pulmonary artery band.
A newborn with double outlet right ventricle, malposed great vessels, hypoplastic aortic arch, and coarctation of the aorta with no restriction to pulmonary blood flow underwent palliation with arch augmentation and placement of an intraluminal Dacron patch pulmonary artery band (PAB). She subsequently presented in shock because of profound hemolytic anemia. Her intraluminal PAB was taken down and replaced with a traditional extraluminal band with resolution of her hemolysis. It is possible that the use of Dacron for construction of the intraluminal PAB may have contributed significantly to this patient's hemolytic anemia.


The cone pedicle, a complex synapse in the retina.
Cone pedicles, the synaptic terminals of cone photoreceptors, are connected in the macaque monkey retina to several hundred postsynaptic dendrites. Using light and electron microscopy, we found underneath each cone pedicle a laminated distribution of dendritic processes of bipolar and horizontal cells. Superimposed were three strata of glutamate receptor (GluR) aggregates, including a novel layer of glutamate receptors clustered at desmosome-like junctions. They are, most likely, postsynaptic densities on horizontal cell dendrites. GABA(A) and GABA(C) receptors are aggregated on bipolar cell dendrites in a narrow band underneath the cone pedicle. Glutamate released from cone pedicles and GABA released from horizontal cell dendrites act not only through direct synaptic contacts but also (more so) through diffusion to the appropriate receptors.


New insights into the role of ID proteins in breast cancer metastasis: a MET affair.
The establishment of lethal metastases depends on the capacity of a small number of cancer cells to regenerate a tumor after entering a target organ. Stankic and colleagues have identified a role for the inhibitor of differentiation protein, ID1, as a critical regulator of breast cancer stem-like properties and metastatic colonization. Under the control of tumor growth factor-beta signaling, ID1 induces mesenchymal-epithelial transition at the metastatic site by antagonizing the activity of the basic helix-loop-helix transcription factor Twist1. This study sheds light on mechanisms that initiate metastatic outgrowth, and strengthens the concept that epithelial-mesenchymal plasticity is crucial at different stages of metastasis.


Serum Autotaxin Activity Correlates With Pruritus in Pediatric Cholestatic Disorders.
Pruritus is a common symptom of cholestatic liver disorders. The present study aimed at evaluating autotaxin (ATX), a lysophospholipase recently identified as potential cause for cholestatic pruritus, in pediatric cholestatic diseases presenting with or without itching. A cohort of 45 children consisting of 14 patients experiencing itching (Alagille syndrome [n = 10], complete extrahepatic biliary atresia [n = 2], neonatal sclerosing cholangitis (n = 1), progressive familial intrahepatic cholestasis type 2 [n = 1]), 9 patients with bile acid synthesis defects (3β-hydroxy-C27-steroid-oxidoreductase [n = 7] and Δ-3-oxosteroid-5β-reductase deficiency [n = 2]), and 22 healthy children were studied. Serum ATX activity and total serum bile salt were determined enzymatically, ATX protein content was semiquantified by Western blotting. Using real-time polymerase chain reaction, ATX mRNA expression was studied in HepG2 cells treated with farnesoid-X-receptor agonists or vehicle. Serum ATX activity was increased in pruritic children with Alagille and other cholestatic syndromes (mean ± standard deviation: 16.1 ± 4.3 nmol · mL · min) compared with children with nonpruritic cholestatic diseases with bile acid synthesis defects (10.4 ± 4.7 nmol · mL · min; P < 0.01) and healthy controls (7.6 ± 2.3 nmol · mL · min; P < 0.001). ATX protein levels closely correlated with serum ATX activity. Serum ATX activity and total serum bile salt showed a linear correlation with itch intensity (r = 0.66, P < 0.001 and r = 0.80, P < 0.001, respectively). No correlation was observed between ATX activity and bilirubin. ATX mRNA expression in HepG2 cells was not induced by farnesoid-X-receptor ligands. Serum ATX activity correlated with itch intensity in children with cholestatic diseases. Bile salts did not increase ATX expression in vitro. ATX inhibitors may be useful antipruritic agents in pediatric cholestatic disorders.


Scalp Lesions in a Pediatric Patient with Hyper IgM Syndrome: Clinical and Histologic Mimicry of Cryptococcus neoformans Infection.
We report a case of cutaneous cryptococcosis due to Cryptococcus neoformans in a pediatric patient with hyper IgM syndrome with scalp lesions that resembled tinea capitis on gross examination and mimicked juvenile xanthogranuloma on histologic examination. This case highlights the importance of considering cutaneous cryptococcosis in patients with hyper IgM syndrome.


Towards models for the prediction of beef meat quality during cooking.
Heating of beef muscles modifies the water content, the micronutrient content and the colour of beef meat. Juice expelling and loss of water soluble micronutrients were predicted by combined transfer-kinetics models. Kinetics modeling and crust formation are needed to progress toward a reliable prediction of HAAs formation. HAAs formation in uniformly heated beef meat slices was compared with the values issued from the kinetic models developed in literature in liquid systems. The models of literature were adapted to meat slices but the parameter values were different from those determined in liquid systems. Results in meat slices were confronted to the HAAs formation at the surface of bigger meat pieces subjected to air roasting conditions. The transposition of the results from the meat slices towards the bigger meat pieces was not direct because the formation of HAAs was affected by the thickening of the crust and the migration of precursors.


Extraction of phenolic compounds from virgin olive oil by deep eutectic solvents (DESs).
Deep eutectic solvents (DESs) are "green" solvents, applied in this study for the extraction of phenolic compounds from virgin olive oil (VOO). Different combinations of DES consisting of choline chloride (ChCl) in various mixing ratios with sugars, alcohols, organic acids, and urea, as well as a mixture of three sugars were used. The yields of the DES extractions were compared with those from conventional 80% (v/v) methanol/water. DES showed a good solubility of phenolic compounds with different polarities. The two most abundant secoiridoid derivatives in olive oil, oleacein and oleocanthal, extracted with ChCl/xylitol and ChCl/1,2-propanediol showed an increase of 20-33% and 67.9-68.3% with respect to conventional extraction, respectively. To our knowledge, this is the first time that phenolic compounds have been extracted from VOO oil using DES. Our results suggest that DES offers an efficient, safe, sustainable, and cost effective alternative to methanol for extraction of bioactive compounds from VOO.


Left atrial structural and functional remodeling following balloon mitral valvuloplasty.
Mitral stenosis (MS) is associated with left atrial (LA) functional and morphological changes as a result of chronic increase in LA pressure. Relieving the mitral obstruction via balloon mitral valvuloplasty (BMV) might be associated with LA structural and functional remodeling. To study alterations of LA volume and functions 1 year following successful BMV in patients with isolated rheumatic severe mitral stenosis. Thirty patients (median age 33 years, 22 women) with severe rheumatic MS were included in the study. Using biplane method, trans-thoracic 2D echocardiography was used to estimate LA volume indexed to body surface area (BSA). Maximal, minimal and pre-A left atrial volumes were measured and indexed to BSA. LA volumetric functions were then assessed and the measurements were repeated 6 months and 1 year after successful valvuloplasty. At baseline, median mitral valve area (MVA) was 0.9 (0.6-1.3) cm2 measured by planimetry with a mean pressure gradient of 12.5 (8-24) mmHg. Following BMV, a significant regression of left atrial volume index was noticed at 6 months compared to baseline (51 vs. 60 ml/m2, p = 0.001) with a further decrease at 1 year (48 vs. 51 ml/m2, p = 0.03). At 6 months, volumetric assessment of left atrial functions showed a significant improvement in LA total emptying fraction (42% vs 30%, p = 0.001) as well as in LA passive emptying fraction (26% vs 14%, p = 0.033) and LA active emptying fraction (20% vs. 18%, p = 0.016). All these indices showed further improvement at 1 year [47% (P = 0.02), 29% (p = 0.03) and 31% (p = 0.001) respectively]. In patients with isolated rheumatic MS, mitral valvuloplasty was associated with a significant decline of LA volume accompanied by a significant improvement of its volumetric functions.