Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure.
In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34(+) cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60-85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤ 0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼ 30-35% apoptotic cells for 2 Gy carbon ions compared to ∼ 25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼ 70% and ∼ 40% for 1 Gy of carbon ions and X-rays, respectively), with a higher fraction of non-transmissible aberrations. In contrast, for both radiation qualities the percentage of clones with chromosomal abnormalities was similar (40%). Using the frequency of colonies with clonal aberrations as a surrogate marker for the leukemia risk following radiotherapy of solid tumors, charged particle therapy is not expected to lead to an increased risk of leukemia in patients.


PHOX2B mutation in a Taiwanese newborn with congenital central hypoventilation syndrome.
Congenital central hypoventilation syndrome (CCHS) is characterized by defective automatic regulation of breathing, mostly during sleep. The diagnostic criteria of CCHS include persistent sleep hypoventilation without primary cardiac, pulmonary disease or neuromuscular dysfunction, and no arousal response to hypoxemia and hypercapnia. Mutations in the PHOX2B gene have been indentified in 93-100% of patients with CCHS. We report a CCHS case with presentation of hypoventilation during sleep and Hirschsprung disease; moreover, a genetic study of the patient confirmed the PHOX2B gene mutation as polyanaline stretch.


DNA methylation in pancreatic cancer: protocols for the isolation of DNA and bisulfite modification.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor and still remains a challenge for its lack of effective therapeutic strategies, which is due to the late diagnosis of this disease. Methylation markers might improve early detection and surveillance of PDAC. Furthermore, analysis of hypermethylation in the tumor tissue might help to identify new targets for therapeutic intervention and improve the understanding of the pathophysiological changes occurring in pancreatic cancer. Methylation specific PCR is the method of choice if a small number of genes will be tested in a larger set of patient samples. After DNA isolation by standard procedure, the DNA is then modified using sodium bisulfite. This DNA can then be used in qualitative and quantitative PCR assays.


Remediation of soil polluted with Pb and Cd and alleviation of oxidative stress in Brassica rapa plant using nanoscale zerovalent iron supported with coconut-husk biochar.
Accumulation of toxic elements by plants from polluted soil can induce the excessive formation of reactive oxygen species (ROS), thereby causing retarded plants' physiological attributes. Several researchers have remediated soil using various forms of zerovalent iron; however, their residual impacts on oxidative stress indicators and health risks in leafy vegetables have not yet been investigated. In this research, nanoscale zerovalent iron supported with coconut-husk biochar (nZVI-CHB) was synthesized through carbothermal reduction process using Fe2O3 and coconut-husk. The stabilization effects of varying concentrations of nZVI-CHB and CHB (250 and 500 mg/kg) on cadmium (Cd) and lead (Pb) in soil were analyzed, and their effects on toxic metals induced oxidative stress, physiological properties, and antioxidant defence systems of the Brassica rapa plant were also checked. The results revealed that the immobilization of Pb and Cd in soil treated with CHB was low, leading to a higher accumulation of metals in plants grown. However, nZVI-CHB could significantly immobilize Pb (57.5-62.12%) and Cd (64.1-75.9%) in the soil, leading to their lower accumulation in plants below recommended safe limits and eventually reduced carcinogenic risk (CR) and hazard quotient (HQ) for both Pb and Cd in children and adults below the recommended tolerable range of <1 for HQ and 10-6 - 10-4 for CR. Also, a low dose of nZVI-CHB significantly mitigated toxic metal-induced oxidative stress in the vegetable plant by inhibiting the toxic metals uptake and increasing antioxidant enzyme activities. Thus, this study provided another insightful way of converting environmental wastes to sustainable adsorbents for soil remediation and proved that a low-dose of nZVI-CHB can effectively improve soil quality, plant physiological attributes and reduce the toxic metals exposure health risk below the tolerable range.


Infants' representations of the infant body in the first year of life: a preferential looking time study.
Representing others' bodies is of fundamental importance for interacting with our environment, yet little is known about how body representations develop. Previous research suggests that infants have expectations about the typical structure of human bodies from relatively early in life, but that these expectations are dependent on how closely the stimuli resemble the bodies infants are exposed to in daily life. Yet, all previous studies used images of adult human bodies, and therefore it is unknown whether infants' representations of infant bodies follow a similar developmental trajectory. In this study we investigated whether infants have expectations about the relative size of infant body parts in a preferential looking study using typical and disproportional infant bodies. We recorded the looking behaviour of three groups of infants between 5 and 14 months of age while they watched images of upright and inverted infant bodies, typical and proportionally distorted, and also collected data on participants' locomotor abilities. Our results showed that infants of all ages looked equally at the typical and proportionally distorted infant body stimuli in both the upright and inverted conditions, and that their looking behaviour was unrelated to their locomotor skills. These findings suggest that infants may need additional visual experience with infant bodies to develop expectations about their typical proportions.


Prognostic Nomogram for Overall Survival in Small Cell Lung Cancer Patients Treated with Chemotherapy: A SEER-Based Retrospective Cohort Study.
Small cell lung cancer (SCLC) is known for its rapid clinical progression and poor prognosis. In this study, we sought to establish a prognostic nomogram among SCLC patients who received chemotherapy. We obtained 4971 SCLC patients' clinical information from the Surveillance, Epidemiology, and End Results (SEER) database for the period between 2004 and 2015. Patients were divided into training and validation sets. Two nomograms were established based on limited stage (LS) and extensive stage (ES) SCLC patients to predict 1-, 2-, and 3-year overall survival (OS) incorporating superior parameters from multivariate Cox regression. Receiver-operating characteristic curves (ROCs) were applied to assess the discrimination ability of the nomogram while the calibration plots were applied to verify the model. Kaplan-Meier method was applied to find survival curves. Decision curve analysis (DCA) was applied to compare OS between the nomograms and 7th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system. Four and six clinical parameters were identified as significant prognostic factors for LS-SCLC and ES-SCLC patient's OS, respectively. The ROC curves indicated satisfactory discrimination capacity of the nomogram, with 1-, 2-, and 3-year area under curve (AUC) values of 0.89, 0.81, and 0.79 in LS-SCLC patients and 0.71, 0.66, and 0.66 in ES-SCLC patients, respectively. Calibration curves indicated that the nomogram showed good agreement with actual observations in survival rate probability. The survival curves among the LS-SCLC and ES-SCLC cohorts were consistent with the high-risk group having a worse prognosis than the low-risk group. Moreover, ROC and DCA curves showed our nomograms had more benefits than the 7th AJCC-TNM staging system. We established two nomograms that can present individual predictions of OS among LS-SCLC and ES-SCLC patients who received chemotherapy. These proposed nomograms may aid clinicians in treatment strategy and design of clinical trials.


Inclusion of a tannin-rich legume in the diet of beef steers reduces greenhouse gas emissions from their excreta.
The objectives of this study were to determine the emission of nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2), as well as the isotopic composition of N2O from excreta of beef steers fed 'AU Grazer' sericea lespedeza hay [SL; Lespedeza cuneata (Dum. Cours.) G. Don]. Fifteen Brahman × Angus crossbred steers were fed one of three experimental diets: 0, 50, or 100% inclusion of SL into 'Tifton 85' bermudagrass hay (Cynodon spp.). Gas sampling occurred on days 0, 1, 3, 5, 7, 14, 18, 25, and 32 after urine or feces application to static chambers for two experimental periods. Effect of the day after feces application (P < 0.001), while day × inclusion of SL interaction was observed in urine (P < 0.001) for all greenhouse gases (GHG) analyzed. Peaks of emission of all GHG in urine and feces occurred in the first days (P < 0.001), with days 3 and 5 being most depleted in 15N-N2O in feces, and days 3, 5, and 7, in urine (P < 0.001). Feeding SL to beef steers was effective in mitigating the emission of GHG from the excreta, but further research is necessary to investigate the mechanisms behind the reductions.


Binding of oxygen and carbon monoxide to the hemocyanin from the spiny lobster.
A high precision, two-dimensional study of oxygen and carbon monoxide binding to Panulirus interruptus hemocyanin has been carried out. Global data analysis of three types of experiments, probing the molecule in its various states of CO and O2 ligation, revealed the entire hexamer to be the basic allosteric unit involved in a two-state mechanism. The co-operativity and linkage of the two ligands are presented in terms of derivative Hill plot surfaces extended along co-ordinates of CO and O2 activities giving a detailed and comprehensive view of the binding behavior. Among the findings is an apparent high co-operativity of carbon monoxide binding at high oxygen activity. The results are discussed in view of a general mechanism for co-operative behavior found in larger hemocyanin aggregates concerning "nested" allosteric interactions.


A material flow analysis on current electrical and electronic waste disposal from Hong Kong households.
A material flow study on five types of household electrical and electronic equipment, namely television, washing machine, air conditioner, refrigerator and personal computer (TWARC) was conducted to assist the Government of Hong Kong to establish an e-waste take-back system. This study is the first systematic attempt on identifying key TWARC waste disposal outlets and trade practices of key parties involved in Hong Kong. Results from two questionnaire surveys, on local households and private e-waste traders, were used to establish the material flow of household TWARC waste. The study revealed that the majority of obsolete TWARC were sold by households to private e-waste collectors and that the current e-waste collection network is efficient and popular with local households. However, about 65,000 tonnes/yr or 80% of household generated TWARC waste are being exported overseas by private e-waste traders, with some believed to be imported into developing countries where crude recycling methods are practiced. Should Hong Kong establish a formal recycling network with tight regulatory control on imports and exports, the potential risks of current e-waste recycling practices on e-waste recycling workers, local residents and the environment can be greatly reduced.


Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili.
Nontypeable Haemophilus influenzae is an important cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Several lines of evidence suggest that the bacterium grows as a biofilm in the human respiratory tract. Fifteen clinical isolates from middle ear fluid of children with otitis media and 15 isolates from sputum of adults with COPD were studied in an in vitro assay of biofilm formation. Striking variability among isolates was observed in their ability to form biofilms. Analysis of cell envelopes revealed minimal differences in banding patterns in polyacrylamide gels, alteration of expression of an epitope on lipooligosaccharide, and preservation of expression of selected epitopes on outer membrane proteins P2, P5 and P6 in biofilms compared to planktonically grown cells. A pilus-deficient variant showed a marked impairment in biofilm formation compared to its isogenic parent. Nontypeable H. influenzae forms biofilms in vitro. Clinical isolates show substantial variability in their ability to grow as biofilms. Three major outer membrane proteins (P2, P5 and P6) are expressed during growth as a biofilm. Expression of lipooligosaccharide is altered during growth as a biofilm compared to planktonic growth. Pili are important in biofilm formation. As the role of biofilms in human infection becomes better defined, characterization of biofilms may be important in understanding the pathogenesis of infection and immune response to nontypeable H. influenzae in children with otitis media and adults with COPD.


A linear model for event-related respiration responses.
Cognitive processes influence respiratory physiology. This may allow inferring cognitive states from measured respiration. Here, we take a first step towards this goal and investigate whether event-related respiratory responses can be identified, and whether they are accessible to a model-based approach. We regard respiratory responses as the output of a linear time invariant system that receives brief inputs after psychological events. We derive average responses to visual targets, aversive stimulation, and viewing of arousing pictures, in interpolated respiration period (RP), respiration amplitude (RA), and respiratory flow rate (RFR). We then base a Psychophysiological Model (PsPM) on these averaged event-related responses. The PsPM is inverted to yield estimates of cognitive input into the respiratory system. This method is validated in an independent data set. All three measures show event-related responses, which are captured as non-zero response amplitudes in the PsPM. Amplitude estimates for RA and RFR distinguish between picture viewing and the other tasks. This pattern is replicated in the validation experiment. Existing respiratory measures are based on relatively short time-intervals after an event while the new method is based on the entire duration of respiratory responses. Our findings suggest that interpolated respiratory measures show replicable event-related response patterns. PsPM inversion is a suitable approach to analysing these patterns, with a potential to infer cognitive processes from respiration.


ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription.
Breast cancer is a common malignancy, but the understanding of its cellular and molecular mechanisms is limited. ZFHX3, a transcription factor with many homeodomains and zinc fingers, suppresses prostatic carcinogenesis but promotes tumor growth of liver cancer cells. ZFHX3 regulates mammary epithelial cells' proliferation and differentiation by interacting with estrogen and progesterone receptors, potent breast cancer regulators. However, whether ZFHX3 plays a role in breast carcinogenesis is unknown. Here, we found that ZFHX3 promoted the proliferation and tumor growth of breast cancer cells in culture and nude mice; and higher expression of ZFHX3 in human breast cancer specimens was associated with poorer prognosis. The knockdown of ZFHX3 in ZFHX3-high MCF-7 cells decreased, and ZFHX3 overexpression in ZFHX3-low T-47D cells increased the proportion of breast cancer stem cells (BCSCs) defined by mammosphere formation and the expression of CD44, CD24, and/or aldehyde dehydrogenase 1. Among several transcription factors that have been implicated in BCSCs, MYC and TBX3 were transcriptionally activated by ZFHX3 via promoter binding, as demonstrated by luciferase-reporter and ChIP assays. These findings suggest that ZFHX3 promotes breast cancer cells' proliferation and tumor growth likely by enhancing BCSC features and upregulating MYC, TBX3, and others.


When to Use Cardiovascular Magnetic Resonance in Patients with Heart Failure.
Use of cardiac magnetic resonance (CMR) to aid in diagnosis, management, and prognosis of ischemic and nonischemic cardiomyopathy has advanced tremendously in the past several decades. These advances have expanded our understanding of both ischemic and nonischemic cardiomyopathies while also allowing for new avenues of diagnosis and treatment. This review summarizes key concepts of CMR technology and CMR use in the diagnosis and prognosis in ischemic, infiltrative, inflammatory, and other nonischemic cardiomyopathies and discusses the use of CMR in the patient presenting with ventricular arrhythmia with unclear diagnosis and advances in CMR in the management cardiomyopathy.


Corrigendum: In vivo total or partial hepatectomy followed by ex vivo liver resection and autotransplantation for malignant tumors: a single center experience.
[This corrects the article DOI: 10.3389/fonc.2023.1214451.].


Optic disc cupping characteristics of normal pressure hydrocephalus patients with normal-tension glaucoma.
We examined the potential association of idiopathic normal pressure hydrocephalus (iNPH) with the generation of normal-tension glaucoma (NTG), to explore possible relationships between intracranial pressure (ICP) and the presence of glaucoma, and to compare disc morphology of NTG patients with or without iNPH. We investigated 20 iNPH patients, examined the prevalence of glaucoma, and compared the optic discs of NTG patients with iNPH (n = 11) and age-matched NTG patients without iNPH (n = 16). All data were collected prior to the treatment of iNPH, to eliminate the possibility that the treatment may have contributed to the progression of NTG. The diagnoses of NTG were made using visual field data, intraocular pressure measurements, fundoscopy, and optical coherence tomography (OCT). Using OCT, the optic nerve disc depth was also measured. The ICP was higher in the iNPH with NTG compared to iNPH without NTG (p = 0.0425), and the cupping depths of the discs of NTG patients with iNPH were significantly shallower compared with those of NTG patients without iNPH (p = 0.0097). Based on the difference in cupping depth, NTG patients with iNPH may have a different morphology from typical glaucoma patients, which could in turn reflect a different pathogenesis compared to NTG patients without iNPH.


Exploring Vegan Mothers' Experiences of Making Food Choices for Infants and Young Children.
Our study aimed to explore vegan mothers' experiences and decision-making processes when feeding their children (up to 3 years old). We conducted a qualitative photo-elicitation interview study in the United Kingdom. Eight vegan mothers provided 5 photographs of food choices they had made for their children and completed online photo-elicitation interviews to discuss these images. Data were transcribed verbatim and analyzed using reflexive thematic analysis. Five themes were developed: role modeling eating behavior, shared decision-making, nutritional guidance for vegan parents, fear of judgment for being vegan, and desire for convenience. Findings illustrate the complexity of the decision-making process and highlight the need for targeted resources for vegan parents. There is a need for awareness raising and training for health care professionals and the development of vegan-specific child-feeding resources to facilitate the provision of evidence-based nutritional guidance for vegan parents.


Tandem mass spectrum of a growth hormone secretagogue: amide bond cleavage and resultant gas-phase rearrangement.
Compound 1 [N-[1(R)-[(1,2-dihydro-1-methylsulfonylspiro[3H-indole-3,4'-piperidin]-1'-yl)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide](MW 528) is an orally-active growth hormone secretagogue (GHS). As part of a continual effort to analyze the ESI/MS and MSn data of novel drugs, the ESI/MS and MS/MS data of protonated 1 (m/z 529) are analyzed and reported here. The analyses reveal that under low-energy collision-induced dissociation (CID) in an ion trap or a quadrupole collision cell, protonated 1 undergoes a gas-phase rearrangement to form protonated 3 (m/z 357) which competes with the y- and b-type product ions during the amide bond cleavages of protonated 1. It is proposed that when the b-type ion is formed by cleavage of the piperidine amide bond, piperidine (a neutral species) and the b-ion (a cation) form an ion-neutral complex. In this complex, piperidine functions as a nucleophile to attack the benzylic carbon of the b-ion, and the protonated ether group in the b-ion acts as a leaving group, which results in the migration of the benzylic group to the piperidine amine to form protonated 3. Protonated 2 (an analog of 1) was studied under the same experimental conditions. The results show that protonated 2 undergoes a similar rearrangement to form protonated 3. While this rearrangement is a relatively minor fragmentation process for protonated 1, it is a predominant process for protonated 2. This phenomenon is explained in terms of the proposed ion-neutral-complex mechanism.


Distinction between malignant and normal breast tissue based on endogenous mediators of estradiol binding.
A component of human breast tumors, isolated by chromatographing the cytosol on hydroxylapatite, increased specific estradiol binding by the cytosolic proteins (23/24) while a similarly isolated component of normal sections of the cancerous breasts inhibited sharply the binding (17/17). Using the same procedures, a component isolated from rat uteri excised at proestrus acted like the one from human breast tumors and a component isolated from uteri at the other phases of the cycle acted like the one from normal breast tissue. The described hormone binding differences are revealed in incubations at 37 degrees C with divalent copper present in the incubation mixture.


Therapeutic potential and protection enhancement of mesenchymal stem cell against cisplatin-induced nephrotoxicity using hyaluronic acid-chitosan nanoparticles as an adjuvant.
A newly synthesized nanoplatform of hyaluronic acid and chitosan nanoparticles (HA/CNPs) was applied to improve the therapeutic efficacy and protection of bone marrow mesenchymal stem cells (BM-MSCs) against cisplatin (CDDP)-induced nephrotoxicity in rats. CDDP administration causes significant increases in levels of serum creatinine (SCr), urea, and KIM-1 coupled with significant albumin level falls, as indicative of acute renal dysfunction. Moreover, the level of the antioxidant enzyme (GSH) was significantly decreased, while the levels of lipid peroxidation (MDA) and inflammatory (IL-6) and apoptotic (caspase-3) markers were significantly increased, indicating a decline in the kidney's antioxidant defense and increased inflammation. In contrast, when rats were pre-treated with either MSCs or MSCs-HA/CNPs before receiving CDDP, the levels of SCr, urea, KIM-1, MDA, IL-6, and caspase-3 were significantly decreased with simultaneous significant rises in GSH and albumin, impelling a great improvement in the antioxidant and anti-inflammatory defenses of the kidney as well as its functions. Intriguingly, MSCs-HA/CNPs were more effective against caspase-3 than MSCs alone, revealing the high anti-apoptotic capability of HA/CNPs. This finding suggests that HA/CNPs could effectively protect MSCs from oxidative stress and apoptosis and thus increase their stability and longevity.


Clinical trial of tin mesoporphyrin to prevent neonatal hyperbilirubinemia.
To assess the efficacy of the heme oxygenase inhibitor, tin mesoporphyrin (SnMP), to reduce total bilirubin (TB) levels. Masked, SnMP (4.5 mg kg(-1)), placebo-controlled, multicenter trial of single intramuscular injection to newborns ⩾35 weeks gestational age whose predischarge screening transcutaneous bilirubin (TcB) was >75th percentile. Two hundred and thirteen newborns (median age 30 h) were randomized to treatment with SnMP (n=87) or 'sham' (n=89). We found that the duration of phototherapy was halved. Within 12 h of SnMP administration, the natural TB trajectory was reversed. At age 3 to 5 days, TB in the SnMP-treated group was +8% but sixfold lower than the 47% increase in the sham-treated group (P<0.001). At age 7 to 10 days, mean TB declined 18% (P<0.001) compared with a 7.1% increase among controls. No short-term adverse events from SnMP treatment were noted other than photoreactivity due to inadvertent exposure to white light phototherapy. Early, predischarge SnMP administration decreased the duration of phototherapy, reversed TB trajectory and reduced the severity of subsequent hyperbilirubinemia.


Chemotherapy and hematopoietic stem cell transplantation for adult T-cell lymphoblastic lymphoma: current status and controversies.
Adult T-cell lymphoblastic lymphoma is a relatively rare aggressive type of non-Hodgkin lymphoma with frequent involvement of extranodal sites. Because of the rarity of this malignancy, it is treated variably and often suboptimally, using approaches similar to those used for other types of aggressive non-Hodgkin lymphomas, with the consequence that outcome is often suboptimal. The collective experience in the management of adult T-cell lymphoblastic lymphoma suggests a good outcome for patients with no adverse prognostic factors who are treated with an acute lymphocytic leukemia-like treatment strategy. Patients with adverse prognostic features should be considered for more aggressive therapy-specifically, high-dose chemotherapy and hematopoietic stem cell transplantation. This article will attempt to review the current status of chemotherapy treatment programs and the relative merits of the different hematopoietic stem cell transplantation programs in this disease, particularly in relation to the pathologic and clinical features that correlate with disease prognosis.


Significant clinical response of activated carbon adsorbed-peplomycin against esophageal cancer: a pilot study.
Activated carbon particle adsorbed-peplomycin (PEP-CH) was administered to three patients who had advanced esophageal cancer and its clinical usefulness was evaluated. The PEP-CH was injected endoscopically into the tumor or the adjacent normal esophageal tissue. Case 1 and case 3 were treated by topical injection of PEP-CH with or without surgery and case 2 was subjected to the PEP-CH treatment with radiation. The barium swallow and endoscopic examination exhibited a marked tumor reduction in all the patients at the end of the PEP-CH treatment. Although a marked clinical response was seen, case 1 died of postoperative complication. Two patients were capable of oral food intake after the treatment, which had been impossible before the treatment. There were no serious adverse side effects caused by the PEP-CH treatment in all the patients. PEP-CH should prove valuable as a new form of chemotherapy for the treatment of esophageal cancer patients.


[Effect of Angelica sinensis polysaccharides on lymphocyte proliferation and induction of IFN-gamma].
To study the effect of Angelica sinsensis polysaccharides on lymphocyte proliferation and induction of IFN-gamma. Angelica sinensis polysaccharides(AP) were separated into AP-I, AP-II, AP-III and AP-IV by alcohol deposition with different concentration. The radioactivities of [3H]-TdR uptake by lymphocyte were used to determine the ability of lymphocyte. The bioactivity of IFN-gamma was measured by violet crystalline dying. AP-IV was found to be composed of Ara and Glu in the ratio of 0.99:6.47, the molecular weight was estimated to be 5,600. AP-I and AP-II 100 mg.kg-1 i.p. were found to significantly augment mice splenocyte proliferation, release IFN-gamma and increase IFN-gamma bioactivity. 50 micrograms.mL-1 AP-I, AP-II and AP-III were shown to enhance the proliferative response of the mouse spleen lymphocytes in vitro. AP-I and AP-II showed higher immunoactivity than AP-III, AP-IV had no effect.


Decreased vasoactive intestinal polypeptide-immunoreactivity of parasympathetic neurons and target innervation following long-term sympathectomy.
Following long-term sympathectomy, parasympathetic neurons show increased expression of some catecholaminergic traits. The objective of this study was to determine if, in addition, expression of vasoactive intestinal polypeptide immunoreactivity (VIP-ir) is suppressed in parasympathetic neurons and a glandular target of the rat. Studies were conducted on the rat pterygopalatine ganglion and meibomian gland; the meibomian gland contains dense innervation that is strongly VIP-ir, and 99% of the VIP-ir neurons projecting to this target reside within the pterygopalatine ganglion. Two months following unilateral superior cervical ganglionectomy on postnatal day 30, DBH-ir fibers normally present within the eyelid were absent and there was a marked reduction in number and staining intensity of VIP-ir fibers within the meibomian gland. The percentage of pterygopalatine ganglion neurons displaying DBH-ir was increased from 43 +/- 4 to 65 +/- 2%. However, the percentage of parasympathetic neurons expressing VIP-ir was decreased from 96 +/- 4% to 76 +/- 1%. We conclude that sympathectomy not only enhances expression of some catecholaminergic traits but also suppresses VIP-ir within pterygopalatine ganglion parasympathetic neurons and meibomian gland target.


Identification of differentially expressed genes by means of outlier detection.
An important issue in microarray data is to select, from thousands of genes, a small number of informative differentially expressed (DE) genes which may be key elements for a disease. If each gene is analyzed individually, there is a big number of hypotheses to test and a multiple comparison correction method must be used. Consequently, the resulting cut-off value may be too small. Moreover, an important issue is the selection's replicability of the DE genes. We present a new method, called ORdensity, to obtain a reproducible selection of DE genes. It takes into account the relation between all genes and it is not a gene-by-gene approach, unlike the usually applied techniques to DE gene selection. The proposed method returns three measures, related to the concepts of outlier and density of false positives in a neighbourhood, which allow us to identify the DE genes with high classification accuracy. To assess the performance of ORdensity, we used simulated microarray data and four real microarray cancer data sets. The results indicated that the method correctly detects the DE genes; it is competitive with other well accepted methods; the list of DE genes that it obtains is useful for the correct classification or diagnosis of new future samples and, in general, it is more stable than other procedures. ORdensity is a new method for identifying DE genes that avoids some of the shortcomings of the individual gene identification and it is stable when the original sample is changed by subsamples.


Mechanisms of vasoconstrictor responses to KCl in rat isolated perfused tail arteries: interaction with the alpha 2-adrenoceptor agonist UK14304.
The vasoconstriction in rat tail arteries during exposure to 56 mM KCl for 2-5 min consisted of an initial sharp peak followed by a secondary plateau. Both components were reduced by the alpha 1-adrenoceptor antagonists prazosin and WB4010. In arteries from reserpine-pretreated rats, the plateau was markedly reduced and only slightly further attenuated by prazosin, however the initial peak was not reduced but was now not affected by prazosin. Thus, the response to KCl in arteries from normal rats is partly due to release of noradrenaline, and this occurs to a greater extent in the plateau than in the peak component. Addition of UK14304 during the plateau reduced the vasoconstriction in arteries from normal rats; however, in arteries from reserpine-pretreated rats there was increased vasoconstriction. These effects of UK14304 were abolished by idazoxan and were not affected by prazosin, and can be attributed to prejunctional inhibition of noradrenaline release in arteries from normal rats and postjunctional enhancement of vasoconstriction in arteries from reserpine-pretreated rats.


Intraoperative spontaneous tension pneumothorax during robotic-assisted coronary artery bypass grafting.
Patients undergoing robotic-assisted coronary artery bypass grafting are increasing. Several complications have emerged with the increasing use of minimally invasive procedures. We reported a case of spontaneous tension pneumothorax that developed in the ventilated lung during robotic assisted left internal mammary artery harvesting causing severe hemodynamic instability. A sudden rise of airway pressure occurred, and the patient became hypotensive. Immediately, the surgeon was notified to look at the right pleura. Pneumothorax was identified, the right pleura was opened using robotic arms, and the right lung was decompressed. A small emphysematous bulla was identified and stabled. Proper identification of the procedure-associated complications is essential for timely management. Tension pneumothorax is a potentially fatal complication, especially in patients under positive pressure ventilation.


A kinetic study of the folding of nuclease B, a possible precursor of staphylococcal nuclease A.
Nuclease B, which contains an additional flexible amino acid sequence of 19 amino acid residues bound to the NH2-terminus of nuclease A, an extracellular nuclease of Staphylococcus aureus, has been investigated in order to determine the influence of the extra residues on the refolding of the nuclease A portion from the acid denaturated state by monitoring the change in tryptophan fluorescence using a stopped-flow technique. It was found that the kinetic parameters of this refolding is similar within experimental error for nuclease A and nuclease B for the entire course (up to 40 s) studied. Therefore, the extra residues do not appear to have any detectable effect on the dynamic events involved in the refolding process. Thus, the folding of the nuclease A portion of nuclease B appears to be thermodynamically and kinetically independent of the 19 residues at the amino-terminus.


Illuminating Roman Vishniac: A Career in Biological Photography and Cinematography.
Despite the fame of Roman Vishniac's photography of Jewish communities in pre-Holocaust Europe; what is relatively unknown today to the photography or science communities - despite the recognition it received at the time of its creation - is that Vishniac's major efforts in photography were neither documentary nor artistic. Rather, the vast majority of his lifetime of photographic work focused on the biological world. Reviewed here is the phenomenal scope and quantity of biological photography and cinematography produced by Roman Vishniac over a five-decade period. From zoo animals to the tiniest of microorganisms, from time-lapse studies of vascular physiology to widely distributed biology classroom films, from spreads in LIFE magazine to advertisements for an insect sting analgesic; Vishniac's ability to capture and create images - almost exclusively of living subjects - was sought after by scientific researchers, popular magazines, movie producers, news organizations and commercial entities. Vishniac's body of scientific photography, both still and ciné, often produced by him from initial concept through writing and shooting - in an age before the technological advances in imaging that we all now enjoy - and despite its later eclipse by his own earlier images, was regarded as the finest and most imaginative of its time.


The Association between Migraine and Depression based on miRNA Biomarkers and Cohort Studies.
An association between migraine and Major Depression (MD) has been revealed in a number of clinical studies. Both diseases have affected a large global population. More understanding of the comorbidity mechanism of these two diseases can shed light on developing new therapies for their treatment. To the best of our knowledge, there have not been any researches in the literature based on microRNA (miRNA) biomarkers to investigate the relationship between MD and migraine. In this study, we have discussed the association between these two diseases based on their miRNA biomarkers. In addition to miRNA biomarkers, we have also demonstrated epidemiological evidence for their association based on Taiwan Biobank (TWB) data. Among the 12 migraine miRNA biomarkers, 11 are related to MD. Only miR-181a has no direct evidence to be involved in the mechanism of MD. In addition to the biological biomarker evidence, the statistical analysis using the large-scale epidemiologic data collected from TWB provides strong evidence on the relationship between MD and migraine. The evidence based on both molecular and epidemiological data reveals the significant association between MD and migraine. This result can help investigate the correlated underlying mechanism of these two diseases.


Paeonia lactiflora root decreases lipid accumulation through the induction of lipolysis and thermogenesis via AMPK activation in 3T3‑L1 cells.
Obesity is associated with high risk of mortality globally because obesity is associated with development of diseases such as diabetes, dyslipidemia, fatty liver disease, hypertension, and cancer. The present study aimed to identify the mechanism of action related to the anti‑obesity activity of Paeonia lactiflora root (PLR) based on its effects on lipid droplet accumulation. The inhibitory activity on lipid accumulation was analyzed through Oil‑Red O staining, and the changes in levels of lipid accumulation‑related proteins were analyzed using Western blot analysis. And the contents of triacylglycerol and free glycerol were analyzed using an ELISA Kit. PLR significantly inhibited the accumulation of lipid droplets and triacylglycerol in differentiating 3T3‑L1 cells. PLR increased phosphorylated‑hormone sensitive lipase (HSL), HSL and adipose triglyceride lipase (ATGL) and decreases perilipin‑1 in differentiating and fully differentiated 3T3‑L1 cells. Furthermore, treatment of fully differentiated 3T3‑L1 cells with PLR resulted in increased free glycerol levels. PLR treatment increased levels of peroxisome proliferator‑activated receptor‑gamma coactivator‑1 alpha (PGC‑1α), PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP‑1) in both differentiating and fully differentiated 3T3‑L1 cells. However, the PLR‑mediated increase in lipolytic, such as ATGL and HSL, and thermogenic factors, such as PGC‑1a and UCP‑1, were decreased by inhibition of AMP‑activated protein kinase (AMPK) with Compound C. Taken together, these results suggest that PLR exerted anti‑obesity effects by regulating lipolytic and thermogenic factors via AMPK activation. Therefore, the present study provided evidence that PLR is a potential natural agent for the development of drugs to control obesity.


Low-cost bioanalysis on paper-based and its hybrid microfluidic platforms.
Low-cost assays have broad applications ranging from human health diagnostics and food safety inspection to environmental analysis. Hence, low-cost assays are especially attractive for rural areas and developing countries, where financial resources are limited. Recently, paper-based microfluidic devices have emerged as a low-cost platform which greatly accelerates the point of care (POC) analysis in low-resource settings. This paper reviews recent advances of low-cost bioanalysis on paper-based microfluidic platforms, including fully paper-based and paper hybrid microfluidic platforms. In this review paper, we first summarized the fabrication techniques of fully paper-based microfluidic platforms, followed with their applications in human health diagnostics and food safety analysis. Then we highlighted paper hybrid microfluidic platforms and their applications, because hybrid platforms could draw benefits from multiple device substrates. Finally, we discussed the current limitations and perspective trends of paper-based microfluidic platforms for low-cost assays.


Lifestyle, health and disease: a comparison between Papua New Guinea and Australia.
The proposition that lifestyle is a major determinant of community health is explored by contrasting the features of a rural subsistence community in the highlands of Papua New Guinea and the features of the community in urbanized, industrialized Australia. Reference is made to differences in physical environment, housing, work, social situation, human relationships, patterns of disease, population statistics, diet, growth, obesity, physical fitness, blood lipid concentrations, blood pressure, salt intake and the occurrence of hypertension, diabetes, cardiovascular disease and signs of degenerative changes in various tissues. The Papua New Guinea community is seen as a self-reliant, self-contained, socially cohesive subsistence society whose members are well adapted to their physical and social environment, free from major degenerative cardiovascular diseases, with little overt psychiatric illness, but with a heavy burden of infectious disease, with marginal nutritional levels of degenerative disease and disease from psychological stress. It is clear that health, in its fullest sense, is not the prerogative of any one type of society.


Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer.
An increase in the plasma levels of apoprotein B-containing lipoproteins is the basis of the magnetic resonance (MR) test for cancer. The narrow MR line width reported by Fossel and co-workers to be associated with the presence of malignant disease is due to a relative increase of very low density lipoprotein. In contrast, the plasma from healthy controls, which has a much broader spectrum, has a higher proportion of high density lipoprotein. However, plasma from patients with hyperlipidemia unrelated to cancer also show narrow MR line widths and are therefore a confounding variable. We used magnetic resonance spectroscopy (MRS) to assess the plasma from 253 patients with a range of lipid related diseases and cancer, and 28 controls. A significant difference (p less than or equal to 0.0005) of 10 Hz exists between the mean line width of the controls and hyperlipidemics without malignant disease. However, in patients with solid tumours a difference of 7 Hz (p less than or equal to 0.0005) in the mean values is recorded although there is an overlap of 6 Hz compared with the controls. Moreover the MRS method was not found to distinguish patients with lymphomas from the control population. The index was not found to be related to patient age or tumour burden.


Review article: is Helicobacter pylori transmitted by the gastro-oral route?
The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet to date no satisfactory explanation has been advanced to account for its spread from person to person. This is surprising for a disease that affects 50% of the world's population. Attempts to culture H. pylori from faecal material and saliva have met with difficulty, casting some doubt on the likelihood of a faeco-oral or oro-oral route of transfer. The infection is easily passed from person to person by gastric intubation. The hypothesis advanced in this paper is that the natural route of transmission is by gastric juice, specifically as a result of epidemic vomiting in childhood. This theory is supported by literature indicating that acute infection with H. is characterized by vomiting of achlorhydric mucus that may serve as a vehicle for transmission. The hypothesis is consistent with most of the epidemiological data that have been published on H. pylori infection, including its association with childhood overcrowding, the lack of a fixed hot water supply and disadvantaged social conditions.


Combined effects of ionic strength and enzymatic pre-treatment in thermal gelation of peanut proteins extracts.
Peanut proteins are mostly composed of arachins and conarachins, globular proteins that can form gels under thermal denaturation or enzymatic treatment. We explored here how ionic strength (0.5 M or 0.8 M) and gelation process (a thermal treatment preceded or not by an enzymatic pre-treatment) could affect peanut protein gel properties. Gel formation and final properties were characterized by rheology, and gel structure was observed by confocal microscopy. We found that the ionic strength imposed during protein extraction determines the arachins/conarachins ratio, and that conarachins-rich samples give stronger gels, which is attributed to their higher content in free thiol groups and lysine residues. The gel storage modulus exhibited a power-law dependence with the protein concentration, which exponent depended on the gelation process. Rheological results, together with confocal microscopy imaging, showed that an enzymatic pre-treatment resulted in denser structures than when a simple thermal treatment was applied.


Brain maturation may be arrested in chronic cocaine addicts.
Animal and human newborn studies suggest that exposure to cocaine in utero delays glial maturation and white matter myelination. Postmortem data show that in the frontal and temporal lobes, white matter myelination continues into middle age. Recent magnetic resonance imaging (MRI) data have confirmed continued white matter volume increase in these regions, reaching a maximum at age 47. Thirty-seven male cocaine dependent (CD) and 52 normal control subjects between ages 19 and 47 were evaluated with MRI. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray/white matter contrast. Highly significant positive correlations between white matter volume and age were observed in both the frontal and temporal lobes of the control group (r =.52, p =.0001 and r =.54, p =.0001, respectively); however, CD subjects did not demonstrate any age-related increase in white matter volume of the frontal (r = -.001; p =.99) and temporal (r = -.07; p =.67) lobes in this age range. The age-related expansion in white matter volume occurring in normal control subjects was absent in CD subjects. The findings suggest that in adults, cocaine dependence may arrest normal white matter maturation in the frontal and temporal lobes of addicts who continue using cocaine.


FNTB Promoter Polymorphisms Are Independent Predictors of Survival in Patients with Triple Negative Breast Cancer.
In breast cancer, the promising efficacy of farnesyltransferase inhibitors (FTIs) in preclinical studies is in contrast to only limited effects in clinical Phase II-III trials. The objective of this study was to explore the clinical relevance of farnesyltransferase β-subunit (FNTB) single nucleotide promoter polymorphisms (FNTB-173 6G > 5G (rs3215788), -609 G > C (rs11623866) and -179 T > A (rs192403314)) in early breast cancer. FNTB genotyping was performed by pyrosequencing in 797 patients from a prospective multicentre observational PiA trial (NCT01592825). In the total cohort, the FNTB-173 6G > 5G polymorphism was an independent predictor of RFI (HR = 0.568; 95% CI = 0.339-0.949, p = 0.031), OS (HR = 0.629; 95% CI = 0.403-0.980, p = 0.040) and BCSS (HR = 0.433; 95% CI = 0.213-0.882; p = 0.021), whereas the FNTB-609 G > C polymorphism was an independent predictor of RFI (HR = 0.453; 95% CI = 0.226-0.910, p = 0.026) and BCSS (HR = 0.227; 95% CI = 0.075-0.687, p = 0.009). Subtype analysis revealed the independent prognostic relevance of FNTB promoter polymorphisms, particularly in TNBC but not in luminal or HER2-positive intrinsic subtypes. Finally, we used electrophoretic mobility shift assays (EMSAs) to confirm in vitro that the polymorphism FNTB-173 6G > 5G resulted in the differential binding of nuclear proteins from five different breast cancer cell lines. This is the first study on breast cancer suggesting that FNTB promoter polymorphisms (i) are independent prognostic biomarkers, particularly in patients with early TNBC, and (ii) could modulate FNTB's transcriptional activity.


Radiology of lumbar vertebral pedicles: variants, anomalies and pathologic conditions.
Close scrutiny of the size, shape, density and margins of the pedicles may permit the clinical radiologist to suggest a wide variety of systemic diseases.


Restoration of dystrophin expression in mdx mice by intravascular injection of naked DNA containing full-length dystrophin cDNA.
Duchenne muscular dystrophy (DMD) is a lethal, X-linked, recessive disease caused by a defect in the dystrophin gene. No effective therapy is available. Dystrophin gene transfer to skeletal muscle has been proposed as a treatment for DMD. However, successful treatment for DMD requires restoration of dystrophin in the affected muscle fibers to at least 20% of the normal level. Current gene transfer methods such as intramuscular injection of viral vector or naked DNA can only transfect a small area of muscle, and therefore is of little clinical utility. We have developed a semisystemic method for gene transfer into skeletal muscle of mdx mice, an animal model for DMD. Naked DNA was injected through the tail artery or vein of mice, in which the aorta and the vena cava were clamped at the location just below the kidneys. The DNA solution was thus forced into the blood vessels of both legs. Luciferase gene expression was detected in all muscle groups in both legs. The effects of injection speed, injection volume, and ischemia time on gene expression were also optimized. LacZ staining was used to check the spread of gene expression in muscle. Although the percentage of transfected fibers was modest (approximately 10%), beta-galactosidase was found in all muscle groups of both legs. Finally, plasmid DNA encoding full-length dystrophin gene was injected into mdx mice and widespread restoration of dystrophin protein was observed in all muscles of both hind limbs. In conclusion, these results demonstrate that the semisystemic delivery of naked DNA is a potential approach towards the long-term goal of gene therapy for DMD.


Proliferative diabetic retinopathy with a proliferative membrane that spread anteriorly from the optic disc.
The authors report a case of proliferative diabetic retinopathy in which the proliferating membrane spread from the optic disc to the anterior of the eyeball, and did not appear to involve the posterior precortical vitreous pocket.


Formation of carboxylated and decarboxylated betalains in ripening grains of Chenopodium quinoa by a dual dioxygenase.
Chenopodium quinoa (quinoa) is a pseudo-cereal that forms part of the cultural heritage of Andean countries, and its grains have high nutritional value and potential health benefits. Betalains are nitrogenous water-soluble pigments and bioactive molecules that contribute to these health-promoting properties. Betalains are restricted to plants of the order Caryophyllales, to which quinoa belongs. A new family of betalains has been discovered in the form of unconventional decarboxylated pigments. Here, we show that these pigments accumulate in ripening quinoa grains of fluorescent nature, and are putatively based on a dopamine-cleaving activity. This study describes for the first time the purification and molecular and functional characterization of a 4,5-dopamine extradiol dioxygenase enzyme from plants. It is a monomeric protein with a molecular mass of 34.5 kDa characterized by chromatography, electrophoresis, and time-of-flight mass spectrometry. We demonstrate that this key enzyme has a dual function in a square-shaped biosynthetic pathway towards the formation of both carboxylated and decarboxylated pigments. Enzyme kinetic properties are characterized for the production of 6-decarboxy-betalamic acid and 3,4-dihydroxy-l-phenylalanine-derived betalamic acid, the two structural units of plant pigment in nature. The profile of multiple betalains present in quinoa grains has been reproduced in one-pot bioreactors containing the novel enzyme and two competing substrates.


Bone histomorphometry in patients with chronic renal failure: effect of 1alpha-hydroxyvitamin D3.
Morphometric and dynamic studies of iliac crest bone biopsies were carried out in twelve patients with chronic renal failure (six on chronic haemodialysis and six with renal insufficiency) before and after 6 months of 1alpha-hydroxyvitamin D3 treatment. Pre-treatment biopsies showed signs of osteomalacia and hyperparathyroidism. Biopsies taken during treatment showed changes towards normality, indicating a beneficial effect of 1alpha-hydroxyvitamin D3.


Food allergens and basophil histamine release in recurrent aphthous stomatitis.
The leukocytes from sixty patients with recurrent aphthous stomatitis were tested for histamine release in response to environmental and food antigens. Eighteen patients (30 percent of the population studied) were atopic, and this history of respiratory allergy was confirmed by an in vitro histamine release assay. The nonatopic patients with recurrent aphthous stomatitis had a significantly higher incidence of in vitro histamine release to foods than did control subjects. The leukocytes from twenty-three patients (38 percent) released histamine to food antigens. Patients eliminated foodstuffs in a double-blind trial to correlate the in vitro histamine release to the development of oral ulcers. Only 30 percent of the patients had a decreased incidence of ulcers after eliminating foods which had induced in vitro histamine release. On rechallenge in the double-blind trial, 30 percent of the foods which caused histamine release also correlated to increased incidence of oral lesions. In eight patients ingestion of certain foodstuffs was correlated to oral ulceration by food diaries and elimination-rechallenge in an open-trial basis. However, dietary manipulation did not completely eliminate the ulceration in any of the patients. The results suggest that food sensitivity may play a minor role in the development of recurrent aphthous stomatitis.


2-(Carboxycyclopropyl)glycines: binding, neurotoxicity and induction of intracellular free Ca2+ increase.
The excitatory actions of the eight stereoisomers of 2-(carboxycyclopropyl)glycine (CCG), conformationally rigid glutamate analogues, were analyzed for the glutamate receptor subtypes by means of binding assays with rat brain membranes. All CCG isomers inhibited the binding of [3H]3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid ([3H]CPP) to N-methyl-D-aspartate (NMDA) receptors. The (2S,3R,4S) isomer (L-CCG-IV) was the most potent agonist for the NMDA receptor and its binding potency was 17- and 790-fold higher than that of L-glutamate and NMDA, respectively. The (2S,3S,4R) isomer (L-CCG-III) showed a potent inhibitory activity for [3H]D-aspartate uptake. Further, L-CCG-IV caused a marked increase of intracellular free Ca2+ concentration [( Ca2+]i) and potent neurotoxicity in the single rat cerebral cortical neurons in vitro, and both were blocked effectively by the NMDA antagonists. Significant correlations were observed between neurotoxicity and the increase of [Ca2+]i and [3H]CPP binding affinity to the NMDA receptor.


Lesions of the stria terminalis attenuate the enhancing effect of post-training epinephrine on retention of an inhibitory avoidance response.
This study investigated the effect of the stria terminalis (ST) lesions on the retention facilitation produced by post-training epinephrine. Rats with sham or bilateral ST lesions were trained on a one-trial step-through inhibitory avoidance task and, immediately after training, received saline or one of 3 doses (0.01, 0.1 or 1.0 mg/kg, s.c.) of epinephrine. In the rats with sham ST lesions, all 3 doses of epinephrine significantly enhanced retention performance. Lesions of the ST did not affect retention significantly. However, the lesions attenuated the facilitating effect of epinephrine on retention. These findings suggest that the integrity of the ST, which connects the amygdala and other brain structures, is essential for the effect of epinephrine on memory processes. The possible involvement of the brain structures processing visceral information in the memory modulatory effect of epinephrine is discussed.


Revisiting the Smoking Paradox in Acute Ischemic Stroke Patients: Findings From the Chinese Stroke Center Alliance Study.
Background Smoking is a well-established risk factor for the development of acute ischemic stroke (AIS). However, the "smoker's paradox" suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in-hospital outcomes in patients with AIS in contemporary practice. Methods and Results A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In-hospital outcomes measurement included all-cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital management were used to evaluate the association between smoking and in-hospital outcomes. A propensity score-matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in-hospital outcomes than nonsmokers (all-cause death or discharge against medical advice: 6.0% versus 6.1%; in-hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in-hospital outcomes (all-cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02-1.08]; P<0.001; complications: OR, 1.06 [95% CI, 1.04-1.08]; P<0.001). The excess risk of adverse in-hospital outcomes remained in smoking patients with AIS after propensity score-matching analysis (all-cause death or discharge against medical advice: OR, 1.04 [95% CI, 1.00-1.08]; P=0.034; complications: OR, 1.05 [95% CI, 1.03-1.08]; P<0.001). Conclusions Smoking was associated with increased risk of adverse in-hospital outcomes among patients with AIS in contemporary practice, reinforcing the importance of smoking cessation in patients with AIS.


Kikuchi Disease: A Case Report.
Kikuchi disease, also known as Kikuchi-Fujimoto disease, is a rare, benign cause of cervical lymphadenitis. It is characterized by painful cervical lymphadenopathy with fevers, leukopenia, and an elevated erythrocyte sedimentation rate. It is diagnosed by obtaining a biopsy specimen from a lymph node that shows characteristic histopathologic findings. We highlight a 42-year-old Japanese man who presented with persistent fevers and cervical lymphadenopathy who was misdiagnosed at multiple urgent care facilities and emergency departments. He was eventually diagnosed with Kikuchi disease after a biopsy specimen was obtained from a lymph node 1 month after his symptoms began. He was treated with hydroxychloroquine and prednisone with resolution of his symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although Kikuchi disease has been previously described in various specialty medical journals, the published literature on Kikuchi disease in emergency medicine is relatively scarce. Given that cervical lymphadenopathy is a common presentation to emergency departments, it is important for emergency physicians to be cognizant of Kikuchi disease in the differential diagnosis of cervical lymphadenopathy to prevent misdiagnoses and unnecessary treatments.


Physical status score and trends in anesthetic complications.
Since deaths due to anesthesia have now become rare, emphasis in quality assurance of anesthetic care must focus on morbidity rather than only on mortality. To facilitate comparisons of outcomes, data from a large anesthesia follow-up program (N = 112,000 anesthetics) were used to evaluate the usefulness of the American Society of Anesthesiologists' Physical Status score (PS) as an independent predictor of nonfatal adverse anesthetic complications. For each patient, the anesthesiologist filled out a form containing information about the patient, the anesthetic, the operative procedure, and outcomes in the operating and recovery rooms. Postoperative complications were assessed by a designated anesthesia follow-up nurse. We calculated the PS-specific complication rate by dividing the number of complications to patients in each PS category by the number of anesthetics given to patients in the same category. We found that PS-specific complication rates increased with increasing PS scores for most complications sought. For intraoperative and recovery room complications, the PS-specific rates increased from 1978-80 and 1981-83 as compared to 1975-77. However, there was no increase over time in the rate of postoperative major complications. After adjusting for patient, anesthesia, and surgery-related variables by multiple logistic regression, the relative odds of having an intraoperative or postoperative major complication were increased for patients classified PS2, PS3 and PS4 & 5 as compared to PS1. However, those in higher PS categories were less likely to have a recovery room complication than PS1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


NMR analysis of the closed conformation of syntaxin-1.
The Sec1/Munc18 (SM) protein Munc18-1 and the SNAREs syntaxin-1, SNAP-25 and synaptobrevin form the core of the membrane fusion machinery that triggers neurotransmitter release. Munc18-1 binds to syntaxin-1 folded into a closed conformation and to the SNARE complex formed by the three SNAREs, which involves an open syntaxin-1 conformation. The former interaction is likely specialized for neurotransmitter release, whereas SM protein/SNARE complex interactions are likely key for all types of intracellular membrane fusion. It is currently unclear whether the closed conformation is highly or only marginally populated in isolated syntaxin-1, and whether Munc18-1 stabilizes the close conformation or helps to open it to facilitate SNARE complex formation. A detailed NMR analysis now suggests that the closed conformation is almost quantitatively populated in isolated syntaxin-1 in the absence of oligomerization, and indicates that its structure is very similar to that observed previously in the crystal structure of the Munc18-1/syntaxin-1 complex. Moreover, we demonstrate that Munc18-1 binding prevents opening of the syntaxin-1 closed conformation. These results support a model whereby the closed conformation constitutes a key intrinsic property of isolated syntaxin-1 and Munc18-1 binding stabilizes this conformation; in this model, Munc18-1 plays in addition an active role in downstream events after another factor(s) helps to open the syntaxin-1 conformation.


External and internal factors regulating metabolic rates of an estuarine benthic community.
The structure and metabolism of a soft-sediment estuarine macrofaunal community were measured over an annual cycle at two depth-contours in mesohaline Chesapeake Bay. Additional data for plankton productivity and respiration, as well as seston and sediment organics are also summarized for these communities. Benthic community respiration ranged from 0.24-3.38 g O2 m-2 d-1, and significant differences were detected between the two depths. Similarly, macroinfaunal standing stocks reached 11.2 and 32.3 g (ash free) m-2 for 3 m and 6 m depth communities, respectively, and both exhibited mid-summer declines in abundance. Inferences drawn from these data facilitated a partitioning of benthic community respiration into macrofaunal and meiofaunal/microbial components with a residual term, much of which could be explained statistically by interactions between these two components. A multi-variate statistical model developed from these data matched benthic respiration measurements within 1-2 S.E. Mass-balances of organic carbon were estimated for water column and benthos at the two depthcontours for early and late summer, as well as for an entire, time-weighted year. These various analyses led to the tentative conclusions that this benthic community was regulated by such internal factors as macrofaunal/meiofaunal grazing and "microbial gardening", and by external factors such as temperature and predation by nekton. However, it appears that the ultimate control for this community was the supply of energy from organic carbon.


Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS.
The coronavirus (COVID-19) pandemic, caused by severe acute respiratory system coronavirus 2 (SARS-CoV-2), has created significant challenges for scientists seeking to understand the pathogenic mechanisms of SARS-CoV-2 infection and to identify the best therapies for infected patients. Although ACE2 is a known receptor for the virus and has been shown to mediate viral entry into the lungs, accumulating reports highlight the presence of neurological symptoms resulting from infection. As ACE2 expression is low in the central nervous system (CNS), these neurological symptoms are unlikely to be caused by ACE2-virus binding. In this review, we will discuss a proposed interaction between SARS-CoV-2 and Toll-like receptor 2 (TLR2) in the CNS. TLR2 is an innate immune receptor that recognizes exogenous microbial components but has also been shown to interact with multiple viral components, including the envelope (E) protein of SARS-CoV-2. In addition, TLR2 plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Based on these observations, we hypothesize that TLR2 may play a critical role in the response to SARS-CoV-2 infiltration in the CNS, thereby resulting in the induction or acceleration of AD and PD pathologies in patients.


Isolation and characterization of novel marine Roseobacter clade members producing unique intracellular chromium-rich aggregates.
The marine Roseobacter clade comprises one of the largest fractions of heterotrophic marine bacteria and accounts for about 16% of 16S rRNA gene clones retrieved from marine bacterioplankton. Their global distribution seems to be related to oceanic water masses and their environmental and biogeochemical properties. In this study, we report isolation and characterization of novel Roseobacter clade members from the Yellow Sea, China. Phylogenetic analysis of 16S rRNA gene sequences reveals that the new isolates (YSCB1, YSCB2, YSCB3 and YSCB4) are closely related to uncultured Arctic seawater bacterium R7967 (99.57-100% sequence identity) and to the cultured Roseobacter sp. DSS-1 (99.27-99.76% sequence identity) isolated from the southeastern coastal water of the USA. Interestingly, YSCB strains possess unique intracellular chromium-containing aggregates. Therefore, these novel Roseobacter clade members exhibit a peculiar property in mineral biogeneration.


Differential expression of multiple U1 small nuclear RNAs in oocytes and embryos of Xenopus laevis.
The small nuclear RNA, U1, is a highly conserved, 165 nucleotide long RNA which has been implicated in the processing of mRNA precursors. We present evidence that in the amphibian X. laevis there exist at least seven species of U1 RNA, which differ in sequence but not in length. Strikingly, these RNAs are not coordinately expressed. Two of the U1 RNAs are the predominant U1 species transcribed in the late blastula-early gastrula stages of Xenopus embryogenesis. These two RNAs, designated xU1a and xU1b, are not synthesized in significant amounts in stage 6 oocytes; a different set of U1 RNAs are expressed during late oogenesis. In a Xenopus cultured cell line, all of the U1 RNA species are expressed. Possible functions and developmental significance of these multiple U1 RNA species are discussed.


Design of a new comprehensive continuous monitoring system for environmental radioactive aerosol.
In order to comprehensive monitoring the radioactive isotopes from nuclear facilities, we developed a dual channel spectral monitoring instrument, and realized synchronous measurement for alpha, beta and gamma radionuclides. This article focuses on how to ensure its accuracy, stability and efficiency. First is the accuracy. In order to lower the interference of environmental and detector performance variation, the zero phase shift filter was designed to ensure the accuracy of characteristic peak position. Lorenz fitting algorithm was designed to reduce the effect of spectral low-energy tailing. Multi thread processing was introduced to ensure that there was sufficient time to complete our complex algorithms. Second is the stability. The complicated measuring process was decomposed into several sub-states. A state monitoring method was set up to timely dispose the abnormal operation. Third is the efficiency. Sampling process and measurement process were designed in synchronous to save monitoring time, which is especially useful for environmental low level radioactive monitoring. Continuous test for seven days shows that the detection limit is less than 0.0003Bq/m3 for U, 239Pu, and less than 0.048Bq/m3 for beta and 137Cs.


Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012-2017.
To analyse clinical characteristics, antibiotic susceptibility, and risk factors for mortality in paediatric invasive pneumococcal disease (IPD) in Beijing. Paediatric IPD patients in our hospital were retrospectively collected from 2012 to 2017. Clinical manifestations, laboratory tests, antimicrobial susceptibility and serotype of isolates, and risk factors for mortality of IPD were analysed. Overall, 186 IPD cases were enrolled. The major manifestations were meningitis (76), pneumonia with bacteraemia (60), bacteraemia without focus (21), and pneumonia with empyaema (22). Of 72 cases with underlying diseases, leukaemia (18.0%), congenital heart disease (15.3%), primary immunodeficiency disease (12.5%), nephrotic syndrome (12.5%), and cerebrospinal fluid leakage (12.5%) were most common. In total 96.9% of isolates would have been covered by the pneumococcal conjugate vaccine (PCV13), including 19F (32.8%), 19A (23.4%), 4 (17.2%), and 23F (9.4%). Nonsusceptibility rates of penicillin, cefotaxime, and cefepime among nonmeningitis patients increased between 2012 and 2017; The mortality rate was 21.5%. Meningitis, respiratory failure, multiple organ failure, and white blood cell count < 4000 cells/μL were independent risk factors for mortality. Meningitis was the most common clinical manifestation of IPD, and was frequently associated with death. Strains in the PCV13 vaccine would cover most of the cases, and so wider use of PCV13 should be considered.


Musculoskeletal affections among kidney recipients: prevalence and risk predictors.
The population of kidney recipients (KR) is steadily increasing in Mansoura and more than 1,800 operations were completed. The extent of musculoskeletal affections (MSA) in this population is not fully known. The purpose of this study is to determine MSA in this KR population and find possible risk predictors. Randomly selected KR (n = 117) were subjected to joint examination, joint pain and morbidity measurements and bone mineral density (BMD) estimation. Laboratory measurements included biochemical, haematological and serological variables. The majority of KR (81.2%) were complaining/suffering from MSA. These included bone loss (n = 78), joint pain (n = 63), skeletal muscle affection (n = 21), soft tissue affection (n = 25), and leg bone pain syndrome (n = 7). Serum creatinine and hepatitis PCR serology demonstrated a significant difference (P < 0.05) between KR with MSA and KR without MSA. Negative hepatitis PCR serology was the only significant (P < 0.05) risk predictor for MSA in this population of KR. This study identified MSA in this steadily increasing KR population. That hepatitis infection was a negative risk predictor for MSA in this KR population warrants further studies.


Removal of linear and branched alkylphenols from aqueous solutions with horseradish peroxidase.
Alkylphenols were effectively treated with horseradish peroxidase at pH 7.0 and 30 degrees C in the presence of H(2)O(2) and poly(ethylene glycol) irrespective of the relative position or isomeric form of the alkyl chains. Water-insoluble oligomer precipitates were readily filtered out after enzymatic treatment, and transparent and colorless solutions were obtained for all p- and m-alkylphenols used.


ESE3-positive PSCs drive pancreatic cancer fibrosis, chemoresistance and poor prognosis via tumour-stromal IL-1β/NF-κB/ESE3 signalling axis.
Desmoplastic stroma, a feature of pancreatic ductal adenocarcinoma (PDAC), contains abundant activated pancreatic stellate cells (PSCs). How PSCs promote PDAC progression remains incompletely understood. Effect of epithelium-specific E-twenty six factor 3 (ESE3)-positive PSCs on PDAC fibrosis and chemoresistance was examined by western blot, RT-PCR, immunofluorescence, flow cytometry assay, chromatin immunoprecipitation, luciferase assay, immunohistochemistry and subcutaneous pancreatic cancer mouse model. ESE3 expression increased in PSCs in PDAC tissues compared with those in normal PSCs. Clinical data showed that ESE3 upregulation in PSCs was positively correlated with tumour size, pTNM stage, CA19-9, carcinoembryonic antigen and serum CA242 level. ESE3 overexpression in PSCs was an independent negative prognostic factor for disease-free survival and overall survival amongst patients with PDAC. Mechanistically, the conditional medium from the loss and gain of ESE3-expressing PSCs influenced PDAC chemoresistance and tumour growth. ESE3 directly induced the transcription of α-SMA, collagen-I and IL-1β by binding to ESE3-binding sites on their promoters to activate PSCs. IL-1β upregulated ESE3 in PSCs through NF-κB activation, and ESE3 was required for PSC activation by tumour cell-derived IL-1β. Inhibiting the IL-1β/ESE3 (PSCs)/IL-1β-positive feedback loop is a promising therapeutic strategy to reduce tumour fibrosis and increase chemotherapeutic efficacy in PDAC.


The use of SPECT to evaluate growth cessation of the mandible in unilateral condylar hyperplasia.
In unilateral condylar hyperplasia, for surgical intervention to be effective, the status of condylar bone growth has to be assessed correctly. Previously this assessment relied on serial clinical observations. This study aimed to evaluate the MDP-SPECT method of assessing condylar growth in unilateral condylar hyperplasia. Twenty-six MDP-SPECT of the mandible had been performed; 21 were diagnosed as condylar hyperplasia and five as non-mandibular disease. Three isotope parameters: isotope counts, pixel counts and counts per pixel were summed for each condyle per subject. The percentage difference in isotope uptake of the three parameters between the two condyles was calculated as the ratio of the combined counts of the two sides. These differences significantly correlated with each other (Pearson r=0.78-0.98) and with the clinical status of bone growth (Spearman rho=0.72-0.86). There was a significant difference for the count per pixel between the 'growing' condyle (transaxial, T: 15.05+/-7.14, coronal, C: 12.29+/-7.88), the 'no further growth' condyle (T: 5.22+/-4.08, C: 5.67+/-3.88) and the 'normal' condyle (T: 0.82+/-0.76, C: 1.34+/-0.66). This method was able to separate 'active growth' from 'growth cessation' of the condyle by a single MDP-SPECT of the mandible. However, further studies are needed to confirm this finding.


A temperature-responsive gene in sorghum encodes a glycine-rich protein that interacts with calmodulin.
Imposition of different biotic and abiotic stress conditions results in an increase in intracellular levels of Ca2+ which is sensed by various sensor proteins. Calmodulin (CaM) is one of the best studied transducers of Ca2+ signals. CaM undergoes conformational changes upon binding to Ca2+ and interacts with different types of proteins, thereby, regulating their activities. The present study reports the cloning and characterization of a sorghum cDNA encoding a protein (SbGRBP) that shows homology to glycine-rich RNA-binding proteins. The expression of SbGRBP in the sorghum seedlings is modulated by heat stress. The SbGRBP protein is localized in the nucleus as well as in cytosol, and shows interaction with CaM that requires the presence of Ca2+. SbGRBP depicts binding to single- and also double-stranded DNA. Fluorescence spectroscopic analyses suggest that interaction of SbGRBP with nucleic acids may be modulated after binding with CaM. To our knowledge, this is the first study to provide evidence for interaction of a stress regulated glycine-rich RNA-binding protein with CaM.


The effect of long-term ethanol maternal ingestion and withdrawal on brain regional monoamine and amino acid precursors in 15-day-old rats.
The effects of alcohol on brain monoamines were studied in 15-day-old offspring of rats given ethanol until the 21st day of gestation or the 15th day post partum. Increased noradrenaline concentrations were found in limbic system, hemispheres, diencephalon and brain stem of pups from mothers under alcohol treatment, and in hemispheres, diencephalon and brain stem of pups from deprived mothers. Serotonin and 5-hydroxyindol acetic acid were augmented in limbic system, diencephalon and brain stem of pups from mothers under alcohol whereas tyrosine was decreased in all brain regions studied in pups from alcoholic and deprived mothers. Consequently, chronic ethanol ingestion by pregnant rats has deleterious effects on CNS development of 15-day-old offspring which persists 15 days after alcohol withdrawal.


Riding through the pandemic: Using Strava data to monitor the impacts of COVID-19 on spatial patterns of bicycling.
COVID-19 prompted a bike boom and cities around the world responded to increased demand for space to ride with street reallocations. Evaluating these interventions has been limited by a lack of spatially-temporally continuous ridership data. Our paper aims to address this gap using crowdsourced data on bicycle ridership. We evaluate changes in spatial patterns of bicycling during the first wave of the COVID-19 pandemic (Apr - Oct 2020) in Vancouver, Canada using Strava data and a local indicator of spatial autocorrelation. We map statistically significant change in ridership and reference clusters of change to a high-resolution base map. Amongst streets where bicycling increased, we measured the proportion of increase occurring on pre-existing bicycle facilities or street reallocations compared to streets without. In all our analyses, we evaluate patterns across subsets of Strava data representing recreation, commuting, and ridership generated by women and older adults (55 + ). We found consistent and unique patterns by trip purpose and demographics: samples generated by women and older adults showed increases near green and blue spaces and on street reallocations that increased access to parks, and these patterns were also mirrored in the recreation sample. Commute ridership highlighted distinct patterns of increase around the hospital district. Across all subsets most increases occurred on bicycle facilities (pre-existing or provisional), with a strong preference for high-comfort facilities. We demonstrate that changes in spatial patterns of bicycle ridership can be monitored using Strava data, and that nuanced patterns can be identified using trip and demographic labels in the data.


The Effectiveness of Combining Nonmobile Interventions With the Use of Smartphone Apps With Various Features for Weight Loss: Systematic Review and Meta-analysis.
The effectiveness of smartphone apps for weight loss is limited by the diversity of interventions that accompany such apps. This research extends the scope of previous systematic reviews by including 2 subgroup analyses based on nonmobile interventions that accompanied smartphone use and human-based versus passive behavioral interventions. The primary objective of this study is to systematically review and perform a meta-analysis of studies that evaluated the effectiveness of smartphone apps on weight loss in the context of other interventions combined with app use. The secondary objective is to measure the impact of different mobile app features on weight loss and mobile app adherence. We conducted a systematic review and meta-analysis of relevant studies after an extensive search of the PubMed, MEDLINE, and EBSCO databases from inception to January 31, 2022. Gray literature, such as abstracts and conference proceedings, was included. Working independently, 2 investigators extracted the data from the articles, resolving disagreements by consensus. All randomized controlled trials that used smartphone apps in at least 1 arm for weight loss were included. The weight loss outcome was the change in weight from baseline to the 3- and 6-month periods for each arm. Net change estimates were pooled across the studies using random-effects models to compare the intervention group with the control group. The risk of bias was assessed independently by 2 authors using the Cochrane Collaboration tool for assessing the risk of bias in randomized trials. Overall, 34 studies were included that evaluated the use of a smartphone app in at least 1 arm. Compared with controls, the use of a smartphone app-based intervention showed a significant weight loss of -1.99 kg (95% CI -2.19 to -1.79 kg; I2=81%) at 3 months and -2.80 kg (95% CI -3.03 to -2.56 kg; I2=91%) at 6 months. In the subgroup analysis, based on the various intervention components that were added to the mobile app, the combination of the mobile app, tracker, and behavioral interventions showed a statistically significant weight loss of -2.09 kg (95% CI -2.32 to -1.86 kg; I2=91%) and -3.77 kg (95% CI -4.05 to -3.49 kg; I2=90%) at 3 and 6 months, respectively. When a behavioral intervention was present, only the combination of the mobile app with intensive behavior coaching or feedback by a human coach showed a statistically significant weight loss of -2.03 kg (95% CI -2.80 to -1.26 kg; I2=83%) and -2.63 kg (95% CI -2.97 to -2.29 kg; I2=91%) at 3 and 6 months, respectively. Neither the type nor the number of mobile app features was associated with weight loss. Smartphone apps have a role in weight loss management. Nevertheless, the human-based behavioral component remained key to higher weight loss results.


Toxicity of a family from vacuumed mercury.
A family of four developed toxic blood levels of mercury after the mother vacuumed a spilled jar of liquid mercury from a closet in their apartment. The youngest son developed severe thrombocytopenia which was initially diagnosed as idiopathic thrombocytopenic purpura secondary to viral illness. A possible association between acute mercury toxicity and idiopathic thrombocytopenic purpura has not been previously reported. Chelation therapy with penicillamine for the older child was administered soon after toxic blood mercury levels were known by the physician. Because thrombocytopenia has been reported to occur in up to 5% of patients receiving penicillamine therapy, the younger child was treated with dimercaptosuccinic acid. The mother was also treated with dimercaptosuccinic acid. The father received dimercaprol therapy. The toxic effects and rationale for now outdated therapeutic uses of mercury are discussed.


Interleukin 1 receptor contributes to methamphetamine- and sleep deprivation-induced hypersomnolence.
Methamphetamine-induced wakefulness is dependent on monoamine transporter blockade. Subsequent to methamphetamine-induced wakefulness, the amount of time spent asleep and the depth of sleep are increased relative to baseline sleep. The mechanisms that drive methamphetamine-induced hypersomnolence are not fully understood. We recently observed that methamphetamine exposure elevates the expression of the sleep-promoting cytokine, interleukin-1β in CD11b-positive monocytes within the brain. Here, we sought to determine whether activation of the interleukin 1 receptor (IL1R) drives the increase in the depth and amount of sleep that occurs subsequent to methamphetamine-induced wakefulness. IL1R-deficient mice and wild type control mice were subjected to systemic methamphetamine (1 and 2mg/kg) and saline treatments. The wake-promoting effect of methamphetamine was modestly potentiated by IL1R-deficiency. Additionally, the increase in time spent in NREMS subsequent to methamphetamine-induced wakefulness in wild type mice was abolished in IL1R-deficient mice. The increase in time spent asleep after 3h of behaviorally enforced wakefulness was also abolished in IL1R-deficient mice. Increases in EEG slow wave activity triggered by methamphetamine and sleep deprivation were of equal magnitude in IL1R-deficient and wild type mice. These data demonstrate that IL1R activation contributes to hypersomnolence that occurs after sleep loss, whether that sleep loss is triggered pharmacologically by methamphetamine or through behavioral sleep deprivation.


Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro.
Root extracts from kava-kava (Piper methysticum G. Forst) are clinically used for the treatment of anxiety and restlessness. Due to reported cases of liver toxicity, kava-kava extracts were withdrawn from the market in several countries in 2002. Because the efflux transporter P-glycoprotein (P-gp) is involved in the absorption, distribution, and excretion of many drugs and often participates in drug-drug interactions, we studied the effect of a crude kava extract and the main kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin on the P-gp-mediated efflux of calcein-acetoxymethylester in the P-gp-overexpressing cell line P388/dx and the corresponding cell line P388. The crude extract and the kavalactones showed a moderate to potent inhibitory activity with f2) (concentration needed to double baseline fluorescence) values of 170 microg/ml and 17 to 90 microM, respectively. The f2 value of yangonin could not be determined due to its higher lipophilicity. In conclusion, our results for the first time demonstrate P-gp-inhibitory activity of kava-kava and its components in vitro.


Docosahexaenoic acid domains: the ultimate non-raft membrane domain.
What distinguishes polyunsaturated fatty acids (PUFAs) from less unsaturated fatty acids is the presence of a repeating =CH-CH(2)-CH= unit that produces an extremely flexible structure rapidly isomerizing through conformational states. Docosahexaenoic acid (DHA) with 6 double bonds is the most extreme example. The focus of this review is the profound impact that the high disorder of DHA has on its interaction with cholesterol when the PUFA is incorporated into membrane phospholipids. Results from a battery of biophysical techniques are described. They demonstrate an aversion of DHA for the sterol that drives the lateral segregation of DHA-containing phospholipids into liquid disordered (l(d)) domains that are depleted in cholesterol. These domains are compositionally and organizationally the antithesis of lipid rafts, the much-studied liquid ordered (l(o)) domain that is enriched in predominantly saturated sphingolipids and cholesterol. We hypothesize that the introduction of DHA-rich domains into the plasma membrane where they coexist with lipid rafts is the origin, in part, of the astonishing diversity of health benefits that accrue from dietary consumption of DHA. According to our model, changes in the conformation of signaling proteins when they move between these disparate domains have the potential to modulate cell function.


Arthroscopy Annual Research Awards: Something to Celebrate.
With sincere appreciation to the AANA Education Foundation for their generous support, we announce our Annual Awards for the best Clinical Research, Basic Science Research, Resident/Fellow Research, and Systematic Reviews published in 2021, as well as the Most Downloaded and Most Cited papers published 5 years ago. Also, as is customary and as we require of authors, our editors update their annual disclosures of potential conflicts of interest. Finally, we annually update our masthead, thus introducing a new Associate Editor and many new members of the Editorial Board and Social Media Board.


Spontaneous remission of 2-chlorodeoxyadenosine (2-CdA)-related secondary myelodysplastic syndrome in a patient with refractory Langerhans cell histiocytosis.
Langerhans cell histiocytosis (LCH) is sometimes resistant to conventional chemotherapies, and treatment with 2-chlorodeoxyadenosine (2-CdA) is gaining importance as a salvage treatment for refractory or recurrent LCH. Secondary malignancies such as acute myelogenous leukemia and myelodysplastic syndrome (MDS) due to 2-CdA have recently been reported. However, there have been no reports to date of cases of 2-CdA-related secondary MDS in which spontaneous remission was achieved. Here, we report the case of a 1-year-old boy with an occipital tumor who was diagnosed with LCH by biopsy and underwent chemotherapy. However, the disease relapsed and became refractory to chemotherapy. He received 2-CdA treatment, which was effective. However 6 months after the start of treatment, he developed MDS with chromosomal abnormality of 7q-. After 1-year observation without any intervention, his hematological findings had returned to normal, and the chromosomal abnormality had also disappeared. To our knowledge, this is the first report of 2-CdA-related MDS with spontaneous hematological remission.


Km mutant of acid alpha-glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement.
A male patient is reported with a mutation of acid alpha-glucosidase causing an altered Km toward natural substrates. Cardiac arrhythmia was found at 12 years of age, and he died of heart failure at 15 years. No skeletal muscle involvement was observed either clinically or histologically. Acid alpha-glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4-methylumbelliferyl alpha-D-glucoside. The hydrolysis of glycogen was markedly decreased (14% of the control mean), and the Km for maltose was increased 4-fold and for glycogen 5-fold. The biosynthesis and the posttranslational processing of the mutant enzyme appeared normal, but the total amount of the enzyme was lower than normal. This mutant enzyme comigrated with normal acid alpha-glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid alpha-glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycogenesis II are discussed.


A reliable method for the analysis of human MHC class II alpha and beta chains by Western blotting of IEF gels.
The solubility and ensuing transfer problems associated with IEF separation and blotting of membrane proteins have been eliminated by confining NP40 to the sample region of the gel and replacing it with octylglycoside in the separating gel. This permitted excellent separation of both the alpha and beta chains of the human MHC antigens and their subsequent detection by Western blotting.


The relationship between paediatric nurses' quality of life and intent to leave: The moderating role of hospital type.
Different types of hospitals exist in Jordan, and each type has its own leadership style. This might affect the nursing workforce in terms of quality of life and intent to leave. This study aimed at (1) assessing the relationship between paediatric nurses' quality of life and intent to leave, (2) examining the moderating effect of the hospital type on this relationship, (3) comparing the quality of life of paediatric nurses working at ministry of health and the University-Affiliated hospitals and (4) exploring the determinants of nurses' intent to leave. A cross-sectional, comparative and correlational design was used in this study. A multi-site sample was selected from two types of hospitals in Jordan; the ministry of health and the University-Affiliated hospitals. A sample of 225 paediatric nurses responded to the brief quality of life questionnaire by the World Health Organization in addition to a group of sociodemographic and work-related questions. Nurses' quality of life and intent to leave were negatively correlated. This correlation was moderated by the type of hospital. Nurses' quality of life was significantly different in the two types of hospitals. Both salary and nursing care model predicted paediatric nurses' intent to leave. The managerial style and work environment of the ministry of health hospitals should be benchmarked against the University-Affiliated hospitals.


Sequential generation of antibody diversity during B-cell development.
It has become increasingly apparent that generation of and variation in antigen-combining sites of antibodies occurs sequentially during B-cell development. Allelic and isotypic exclusion mechanisms ensure that a B cell produces antibody molecules having a single kind of combining site. A major reason for evolution of mechanisms which result in asynchronous formation of functional H and L chain genes may be the need for allelic and isotypic exclusion; but this may not be the only advantage of asynchronous formation of H and L chain genes. The evolution of mechanisms causing nonjunctional somatic mutation late in B cell development - only after antigen exposure apparently - may result from the biological advantages of: (1) 'fine tuning' of the combining site; (2) a response to an anti-idiotype regulatory network, or (3) expanded memory.


Hepatic potential of bone marrow stromal cells: development of in vitro co-culture and intra-portal transplantation models.
Bone marrow comprises heterogeneous cell populations and is thought to contain certain progenitors with the ability to differentiate into multiple mesenchymal cell lineages. To identify any differentiation plasticity of adult bone marrow stromal cells (BMSCs) into hepatocyte-like phenotypes, we developed a co-culture model with damaged liver tissue and an animal model of engraftment in cirrhotic liver via intra-portal transplantation. After 10 days of co-culture with injured liver tissues, BMSC expressed specific markers for hepatocytes by RT-PCR and Western blot. The two animal models for liver injury employed used carbon tetrachloride (CCl4) induction or bile duct ligation. For tracing BMSC resident in the liver after intra-portal transplantation, green fluorescent protein (GFP)-positive BMSCs or in situ hybridization of Y-chromosome Sry gene in male BMSC were used in a cross-sex transplantation model. Expression of hepatocyte-specific markers in recipients' liver tissues was determined by fluorescence immunohistochemistry. Our findings demonstrated that about 16% parenchyma cells were GFP-positive cells derived from infused BMSCs, and expression of albumin was detected in these cells in engrafted liver tissues. In conclusion, BMSCs exhibited hepatocyte-like phenotypes after co-cultivation with liver tissue and transplanted into the injured liver. The presented evidence indicated the trans differentiation potential of BMSC developing to the hepatocytes.


Optimizing the assessment of suicidal behavior: The application of curtailment techniques.
Given their length, commonly used scales to assess suicide risk, such as the Beck Scale for Suicide Ideation (SSI) are of limited use as screening tools. In the current study we tested whether deterministic and stochastic curtailment can be applied to shorten the 19-item SSI, without compromising its accuracy. Data from 366 patients, who were seen by a liaison psychiatry service in a general hospital in Scotland after a suicide attempt, were used. Within 24h of admission, the SSI was administered; 15 months later, it was determined whether a patient was re-admitted to a hospital as the result of another suicide attempt. We fitted a Receiver Operating Characteristic curve to derive the best cut-off value of the SSI for predicting future suicidal behavior. Using this cut-off, both deterministic and stochastic curtailment were simulated on the item score patterns of the SSI. A cut-off value of SSI≥6 provided the best classification accuracy for future suicidal behavior. Using this cut-off, we found that both deterministic and stochastic curtailment reduce the length of the SSI, without reducing the accuracy of the final classification decision. With stochastic curtailment, on average, less than 8 items are needed to assess whether administration of the full-length test will result in an SSI score below or above the cut-off value of 6. New studies using other datasets should re-validate the optimal cut-off for risk of repeated suicidal behavior after being treated in a hospital following an attempt. Curtailment can be used to simplify the assessment of suicidal behavior, and should be considered as an alternative to the full scale.