Cancer Patients' Perceived Difficulties Filling Opioid Prescriptions After Receiving Outpatient Supportive Care.
Limited access to opioids for patients with cancer has been reported as a potential unintended consequence of recent regulations restricting opioid use and prescribing practices. To our knowledge, there are a limited number of peer-reviewed studies that evaluate the perceived difficulties of the patients with cancer when filling their opioid prescription. To understand these difficulties, we surveyed patients receiving opioids in our outpatient supportive care center (SCC). The primary objective of this study was to evaluate cancer patients' perceptions of overall difficulties when filling their opioid prescription. Secondary objectives included determining associations between patient characteristics and difficulty and comparing difficulty between filling opioid and nonopioid prescriptions. Patients with cancer receiving opioids that had been seen two times or more at our SCC were asked to complete a survey. The information collected included patient demographics, clinical characteristics, and patients' experiences filling their opioid prescription. The patients' median age was 60 years; 54% were female and 69% were white. Forty-four patients (32%) reported that they have experienced difficulty filling their opioid prescription. More than 25% of those 44 patients perceived difficulty from interactions with the pharmacy and/or pharmacist. Forty-six patients (33%) reported more difficulty filling their opioid prescriptions than filling their nonopioid prescriptions. This study provides evidence that patients with cancer visiting our SCC perceived difficulties obtaining their opioid prescriptions. The results suggest that negative interactions with the pharmacy and/or pharmacist contribute to their perceived difficulty. Additional research is needed to further characterize the contributors of the difficulties patients with cancer face in filling their opioid prescriptions.


Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation.
Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE(2)) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20-30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation.


Excited states of GFP chromophore and active site studied by the SAC-CI method: effect of protein-environment and mutations.
Excited states of fluorescent proteins were studied using symmetry-adapted cluster-configuration interaction (SAC-CI) method. Protein-environmental effect on the excitation and fluorescence energies was investigated. In green fluorescent protein (GFP), the overall protein-environmental effect on the first excitation energy is not significant. However, glutamine (Glu) 94 and arginine (Arg96) have the red-shift contribution as reported in a previous study (Laino et al., Chem Phys 2004, 298, 17). The excited states of GFP active site (GFP-W22-Ser205-Glu222-Ser65) were also calculated. Such large-scale SAC-CI calculations were performed with an improved code containing a new algorithm for the perturbation selection. The SAC-CI results indicate that a charge-transfer state locates at 4.19 eV, which could be related to the channel of the photochemistry as indicated in a previous experimental study. We also studied the excitation and fluorescence energies of blue fluorescent protein, cyan fluorescent protein, and Y66F. The SAC-CI results are very close to the experimental ones. The protonation state of blue fluorescent protein was determined. Conformation of cyan fluorescent protein indicated by the present calculation agrees to the experimentally observed structure.


Isolation by molecular cloning of a fragment in the split ovalbumin gene.
An EcoRI fragment of chicken DNA (fragment 'a') containing a sequence complementary to the 3' half of ovalbumin mRNA has been isolated by molecular cloning. Analysis of the cloned fragment proves conclusively that the chicken ovalbumin gene is split. Fragment 'a' contains no extensive sequence repeated elsewhere in the genome and represents the only type of organisation of this part of the split ovalbumin gene in chicken genome.


Pulmonary resection of lung cancer in a patient with partial anomalous pulmonary venous connection.
We report a case of a 64-year-old man in whom a partial anomalous pulmonary venous connection (PAPVC) was found before right lower lobectomy for lung cancer. In addition to lung cancer, there was a right superior pulmonary vein that drained into the superior vena cava (SVC). There was a concern of right ventricular heart failure resulting from increased left-to-right shunt flow after lobectomy. Therefore cardiac catheterization was performed to calculate the pulmonary-to-systemic flow rate in the presence of blocked blood flow to the lower lobe pulmonary artery. As a result, we successfully performed lobectomy without correcting the PAPVC.


Topical non-steroidal anti-inflammatory drugs for central serous chorioretinopathy: A systematic review and meta-analysis.
Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.


Measurement of the clinical status of patients with breast cancer: evidence for the validity of self assessment with linear analogue scales.
We have assessed the validity of a method of measurement for describing the clinical status of patients with breast cancer. One hundred and nine patients with breast cancer assigned numerical values to their own state of health using linear analogue scales. We have shown previously that this method of measurement is reliable and corresponds well with other methods of assessment. Validity was assessed in this study by examining the ability of measurements to distinguish between groups of patients who differed either in the presence of metastatic disease or in the treatments they were receiving. All patients completed the same set of 29 linear analogue scales that enquired about the severity of health related problems and symptoms. In general, patients with metastatic disease were clearly distinguished from patients without metastases by their scores on items related to physical function. Patients receiving chemotherapy were distinguished from those not receiving chemotherapy by their scores on treatment related toxicities. Measures of psychological and social health were similar in patients receiving chemotherapy regardless of disease status. These results provide further support for the validity of measurement of clinical status with linear analogue scales scored by patients.


Myelomeningocele and Kyphosis: Natural History of the Disease and the First Results of a New Surgical Technique.
To define the natural course of kyphosis, and to evaluate the efficiency of a new technique in surgical correction of kyphosis seen in myelomeningocele(MM) patients. We retrospectively reviewed our patients with MM. The rate of kyphosis, mean angle of progression and mean angle of surgical correction were evaluated. Surgical correction was achieved with the same technique in all patients; kyphectomy, short segment instrumentation with plate system and long segment instrumentation with screw-rod system. A total of 14 patients were treated surgically and the mean age at the surgery was 39 months. The incidence of kyphosis rate was %21 in this study. The mean angle of kyphosis was 85.8°. Average angle of progression was 15.7° whereas it was 6.3° degree in patients whose kyphosis angle ?90 and > 90 degree, respectively, at birth. 14 patients were treated surgically and the mean age at the surgery was 39 months. The mean angle of correction of kyphosis was 86 degree. The most common complications were wound dehiscence and cerebro-spinal fluid leak. One patient died 3 months after surgery, and one patient was reoperated due to pull-out of screws. Effective surgical correction of kyphosis in MM patients can be achieved with the described surgical technique even in younger ages. Prospective studies in larger study population are necessary for more accurate definition of natural history of kyphosis in MM patients.


CNS viruses--diagnostic approach.
Diagnosis of CNS viral infections is challenging; yet, significant progress in laboratory diagnosis of CNS infections has come through applications of serology and polymerase chain reaction (PCR) to CSF and tissues. Advances in molecular and laboratory techniques, together with neuroimaging, epidemiologic, and surveillance efforts, are yielding greater success in CNS viral diagnosis and treatment.


The Composite Face Effect Between Young and Older Chinese Adults Remains Stable.
Holistic face perception is often considered to be a cornerstone of face processing. However, the development of the ability to holistically perceive faces in East Asian individuals is unclear. Therefore, we measured and compared holistic face processing in groups of Chinese children, young adults, and older adults by employing the complete composite face paradigm. The results demonstrate a similar magnitude of the composite effect in all three groups although face recognition performance in the task was better in young adults than in the two other groups. These findings suggest that holistic face perception in Eastern individuals is stable from late childhood to at least age 60, whereas face memory may be subject to later development and earlier decline.


Design and engineering of whole-cell biocatalyst for efficient synthesis of (R)-citronellal.
Bioproduction of optical pure (R)-citronellal from (E/Z)-citral at high substrate loading remains challenging. Low catalytic efficiency of (R)-stereoselective ene reductases towards crude citral mixture is one of the major bottlenecks. Herein, a structure-based engineering strategy was adopted to enhance the catalytic efficiency and stereoselectivity of an ene reductase (OYE2p) from Saccharomyces cerevisiae YJM1341 towards (E/Z)-citral. On basis of homologous modelling, molecular docking analysis and alanine scanning at the binding pocket of OYE2p, a mutant Y84A was obtained with simultaneous increase in catalytic efficiency and stereoselectivity. Furthermore, site-saturation mutagenesis of Y84 yielded seven mutants with improved activity and stereoselectivity in the (E/Z)-citral reduction. Among them, the variant Y84V exhibited an 18.3% and 71.3% rise in catalytic efficiency (kcat /Km ) for (Z)-citral and (E)-citral respectively. Meanwhile, the stereoselectivity of Y84V was improved from 89.2% to 98.0% in the reduction in (E/Z)-citral. The docking analysis and molecular dynamics simulation of OYE2p and its variants revealed that the substitution Y84V enabled (E)-citral and (Z)-citral to bind with a smaller distance to the key hydrogen donors at a modified (R)-selective binding mode. The variant Y84V was then co-expressed with glucose dehydrogenase from Bacillus megaterium in E. coli D4, in which competing prim-alcohol dehydrogenase genes were deleted to prevent the undesired reduction in the aldehyde moiety of citral and citronellal. Employing this biocatalyst, 106 g l-1 (E/Z)-citral was completely converted into (R)-citronellal with 95.4% ee value and a high space-time yield of 121.6 g l-1 day-1 . The work highlights the synthetic potential of Y84V, which enabled the highest productivity of (R)-citronellal from (E/Z)-citral in high enantiopurity so far.


A +8 (-->CT) mutation within the 5' untranslated region of beta-globin down-regulates the mRNA transcription.
The 5' untranslated region (5'UTR) of beta-globin has been well characterized and is often used as a model for eukaryotic transcription/translation, but there are still questions regarding the mechanism of translational control. Mutations affecting the Cap site at + 1 and at positions +10, +22, +33 and +40-43 have been described, and it is thought that the initiator element required for transcription stretches from -2 to +7 relative to the Cap site with a downstream element situated from +10 to +15. The influence on initiation or translation of sequences between +7 and +10 is unknown. We report here a family with beta-thalassemia (beta-thal) who have a + 8 (CT) mutation. Molecular studies indicate that this mutation leads to a reduction in mRNA levels and we discuss the implications of a CT change at this position on the transcription/translation process.


Quantitative assessment of hand radiographs of rheumatoid arthritis: interobserver variation in a multicenter radiographic study.
We investigated interobserver variations in the Larsen radiographic scoring method on hand radiographs of rheumatoid arthritis (RA) patients in a multicenter trial and developed a new radiographic scoring method. Thirteen experienced rheumatologists scored 10 representative RA hand radiograms with the Larsen scoring method and clarified the precipitating factors of interobserver variation. Based on this study, it was proved that the ankylotic joint, overlapping joint, and more precise erosive joint are needed for optimal radiographic evaluation. Therefore, we modified the Larsen scoring method on the basis of these precipitating factors and developed a novel radiographic scoring method. Finally, to determine which scoring system was most reliable, the interobserver variation using three methods (original Larsen method, revised Larsen method, our scoring method) were compared by 13 experienced rheumatologists and 13 residents. Our scoring method proved to have simplicity, reliability, and ease of learning. These results suggest that our novel radiological quantitative assessment method has useful applications for clinical studies in patients with RA.


Electron Beam Lithography of Magnetic Skyrmions.
The emergence of magnetic skyrmions, topological spin textures, has aroused tremendous interest in studying the rich physics related to their topology. While skyrmions promise high-density and energy-efficient magnetic memory devices for information technology, the manifestation of their nontrivial topology through single skyrmions and ordered and disordered skyrmion lattices could also give rise to many fascinating physical phenomena, such as chiral magnon and skyrmion glass states. Therefore, generating skyrmions at designated locations on a large scale, while controlling the skyrmion patterns, is the key to advancing topological magnetism. Here, a new, yet general, approach to the "printing" of skyrmions with zero-field stability in arbitrary patterns on a massive scale in exchange-biased magnetic multilayers is presented. By exploiting the fact that the antiferromagnetic order can be reconfigured by local thermal excitations, a focused electron beam with a graphic pattern generator to "print" skyrmions is used, which is referred to as skyrmion lithography. This work provides a route to design arbitrary skyrmion patterns, thereby establishing the foundation for further exploration of topological magnetism.


Immunopurification and protease inhibitory properties of protease nexin-2/amyloid beta-protein precursor.
Protease nexin-2 (PN-2) is a protease inhibitor that is synthesized and secreted by a variety of extravascular cells including human fibroblasts. It forms sodium dodecyl sulfate-stable complexes with trypsin, the epidermal growth factor binding protein and the gamma-subunit of nerve growth factor. Recently we reported that PN-2 is the secreted form of the amyloid beta-protein precursor (APP) and is a potent inhibitor of chymotrypsin. Here we describe a two-step procedure to purify PN-2/APP using a monoclonal antibody immunoaffinity column. We also quantitated the protease inhibitory properties of purified PN-2/APP on a number of serine proteases. PN-2/APP was a potent inhibitor of coagulation factor XIa with a Ki = 2.9 x 10(-10). The inhibition of factor XIa by PN-2/APP was augmented by heparin and resulted in a Ki = 5.5 x 10(-11) M. Trypsin and chymotrypsin were also effectively inhibited with a Ki = 4.2 x 10(-10) and 1.6 x 10(-9), respectively. PN-2/APP also inhibited the epidermal growth factor binding protein, the gamma-subunit of nerve growth factor, and chymase and plasmin to a lesser extent. In view of recent findings that PN-2/APP is contained in alpha-granules of platelets and is secreted upon platelet activation, the potent inhibition of factor XIa suggests that PN-2/APP may play a regulatory role in the coagulation pathway at vascular wound sites. In addition, these studies define biochemical activities of PN-2/APP which may be involved in regulating proteases that lead to the generation and deposition of the beta-protein in neurodegenerative lesions associated with Alzheimer's disease and Down's syndrome.


Protein folding and stability using denaturants.
Measurements of protein folding and thermodynamic stability provide insight into the forces and energetics that determine structure, and can inform on protein domain organization, interdomain interactions, and effects of mutations on structure. This chapter describes methods, theory, and data analysis for the most accessible means to determine the thermodynamics of protein folding: chemical denaturation. Topics include overall features of the folding reaction, advances in instrumentation, optimization of reagent purity, mechanistic models for analysis, and statistical and structural interpretation of fitted thermodynamic parameters. Examples in which stability measurements have provided insight into structure and function will be taken from studies in the author's laboratory on the Notch signaling pathway. It is hoped that this chapter will enable molecular, cell, and structural biologists to make precise measurements of protein stability, and will also provide a strong foundation for biophysics students who wish to undertake experimental studies of protein folding.


Female urinary incontinence: a cross-sectional study from a Thai rural area.
The aims of this study were to investigate the prevalence and associated factors of female urinary incontinence in a Thai rural area and to investigate the impact of female urinary incontinence on quality of life. A population-based cross-sectional survey was performed from September 2003 to February 2004. A total of 1,126 women completed the questionnaires. The overall prevalence of urinary incontinence was 36.50%, i.e. stress urinary incontinence (33.60%), urge urinary incontinence (11.00%) and mixed urinary incontinence (8.07%). Urinary incontinence adversely affected quality of life; the mixed urinary incontinence group reported significantly greater impairment than the stress and urge urinary incontinence groups. Advancing age, labouring occupation, postmenopausal status, years since menopause, medical diseases, childbirth and vaginal delivery were associated with this problem.


Disparities in surgical outcomes of neonates with congenital heart disease across regions, centers, and populations.
To summarize existing literature on neonatal disparities in congenital heart disease surgical outcomes and identify potential policies to address these disparities. Disparities in outcomes for neonatal congenital heart surgery were largely published under four domains: race/ethnicity, insurance type, neighborhood/socioeconomic status, and cardiac center characteristics. While existing research identifies associations between these domains and mortality, more nuanced analyses are emerging to understand the mediators between these domains and other non-mortality outcomes, as well as potential interventions and policies to reduce disparities. A broader look into social determinants of health (SDOH), prenatal diagnosis, proximity of birth to a cardiac surgical center, and post-surgical outpatient and neurodevelopmental follow-up may accelerate interventions to mitigate disparities in outcomes. Understanding the mechanisms of how SDOH relate to neonatal surgical outcomes is paramount, as disparities research in neonatal congenital heart surgery continues to shift from identification and description, to intervention and policy.


Energy budgets do balance-A comment on a paper by Wightman and Rogers.
In a recently published energy budget for the larvae of the leafcutter bee (Wightman and Rogers, Oecologia (Berl.) 36 (1978) 245-257) respiration as estimated by respirometry amounted to only 67% of the respiration as estimated from the difference between assimilation and production. In this note it is shown that this discrepancy seems to result from an incorrect value of the oxycalorific equivalent and that a more reasonable value makes the two estimates of respiration agree.


Case Report of Anti-Thrombogenicity.
The Toray Filtryzer™-NF is a new polymethyl methacrylate filter with improved hemocompatibility and reduced impact on platelet counts. This suggests that, if necessary, a reduction in anticoagulation may be possible when dialysis is performed with the Toray Filtryzer™-NF. In the following, we dialyzed 5 hemodialysis patients who had a contraindication to full anticoagulation postoperatively or after renal biopsy with the Filtryzer™-NF. A significant reduction in heparin administration was achieved, and in 1 patient, heparin substitution was completely omitted. Despite the significantly reduced heparin doses, no thrombosis of the system occurred during the hemodialysis. In conclusion, hemodialysis using the Toray Filtryzer™-NF is an effective alternative for patients at significantly increased risk of bleeding.


Triple hormone-receptor assay: a more accurate predictive tool for the treatment of advanced breast cancer?
In a group of 74 patients with advanced metastatic breast cancer, 57% of those with cytoplasmic oestrogen receptor activity in their tumours (REC+) showed a clinical response to endocrine therapy. Of 51 patients whose tumour was assayed for both REC and cytoplasmic progesterone (RPC) activity, 9/12 patients with REC+ RPC+ tumours responded to hormone treatment, whereas only 3/30 patients with REC-RPC-tumours had a clinical response. In a group of 19 patients in whom nuclear oestrogen receptor (REN) was also estimated in the pellets from tumour-tissue homogenates, 5/6 with tumours positive for all 3 receptors showed a clinical response. None of the 9 patients with triply negative tumours responded. Addition of the REN assay appears to reinforce the greater precision of prediction when RPC as well as REC are estimated in breast tumours.


Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study.
The quantium consciousness index (qCON), an electroencephalography (EEG)-based modality, has no studies regarding intensive care unit (ICU) sedation, though very few studies describe its use for assessing depth of anesthesia in the operation theater. In this study, we evaluated qCON for assessing sedation compared with Richmond Agitation Sedation Scale (RASS) in patients on a mechanical ventilator in the ICU. Eighty-seven mechanically ventilated patients aged between 18 and 60 years were investigated over a 12-hour period. They were given a standardized dosage of sedation comprised of a bolus dose of propofol 0.5 mg/kg and fentanyl 1 µg/kg, and then infusions of propofol 2-5 mg/kg/hour and fentanyl 0.5-2 µg/kg/hour. These drug infusions were adjusted to achieve a RASS score between 0 and -3. Using the qCON monitor, the investigator recorded the qCON values and then assessed the RASS score. A total of 1,218 readings were obtained. After contrasting each qCON value correspondingly with time to each RASS value, we found their correlation to be statistically significant (ρ = 0.288, p <0.0001). With the help of receiver operating characteristic (ROC) curves, we were able to differentiate appropriate from inappropriate levels of sedation. A qCON value of 80 had a sensitivity of 72.67% and a specificity of 67.42% (AUC 0.738 with SE 0.021). qCON can be used for assessing sedation levels in mechanically ventilated critically ill patients. CTRI/2019/07/020064. Harsha MS, Bhatia PK, Sharma A, Sethi P. Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study. Indian J Crit Care Med 2022;26(4):491-495.


Magnetic resonance imaging of lumbar intervertebral discs in elderly patients with minor trauma.
Vertebral body fractures due to minor trauma, which commonly occur in the elderly, are a frequently encountered clinical problem. We utilized MRI in patients with acute back pain following minor injury to ensure the earliest possible diagnosis. Lumbar discs adjacent to fractured vertebral bodies were evaluated, using magnetic resonance imaging (MRI), to elucidate how often these discs were injured and how the injured discs were depicted by MRI. We retrospectively reviewed MR images of 74 discs from 37 elderly patients (>65-year-old) with a single level vertebral fracture (fracture group). Patients with multiple-level fractures, burst fractures and/or major trauma, such as that resulting from a traffic accident, were excluded from this study. We also reviewed MR images of 190 discs from 27 elderly patients diagnosed with lumbar stenosis, who had no previous history of vertebral body fractures (stenosis group). In the fracture group, 23% (17/74) of T1-weighted images exhibited a high-intensity area in the disc, whereas only 3% (5/190) exhibited a high-intensity area in the stenosis group. In some cases, in the T2-weighted images we also found a high-intensity zone in discs that showed low- or iso-intensity. This phenomenon was more frequently observed in the fracture group (47%: 35/74) than in the stenosis group. The present study indicates that, in elderly patients, intervertebral discs adjacent to vertebral fractures resulting from minor trauma are often injured. Because hemorrhage is the most likely cause of a high-intensity T1-weighted image, the results indicate that hemorrhage can be induced in a disc adjacent to a vertebral body fractured by even minor trauma.


Nonspecific suppression of anti-graft immunity by antigen-specific T suppressor cells.
The specificity of T suppressor cells induced by intravenous administration of irradiated allogeneic spleen cells was studied in mice by means of a delayed type hypersensitivity (DTH) assay. T suppressor cells induced by either H-2K, H-2I or H-2D incompatible cells were found to be specific for the inducing alloantigen. Such antigen specific T suppressor cells can suppress the response to another H-2 alloantigen, provided it is administered together with the alloantigen that had induced the T suppressor cells. Similarly, T suppressor cells induced by non-H-2 alloantigens can suppress the response to H-2 alloantigens if administered simultaneously.


Start codon targeted (SCoT) and target region amplification polymorphism (TRAP) for evaluating the genetic relationship of Dendrobium species.
Two molecular marker systems, start codon targeted (SCoT) and target region amplification polymorphism (TRAP), were used for genetic relationship analysis of 36 Dendrobium species collected from China. Twenty-two selected SCoT primers produced 337 loci, of which 324 (96%) were polymorphic, whereas 13 TRAP primer combinations produced a total of 510 loci, with 500 (97.8%) of them being polymorphic. An average polymorphism information content of 0.953 and 0.983 was detected using the SCoT and TRAP primers, respectively, showing that a high degree of genetic diversity exists among Chinese Dendrobium species. The partition of clusters in the unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis plot based on the SCoT and TRAP markers was similar and clustered the 36 Dendrobium species into four main groups. Our results will provide useful information for resource protection and will also be useful to improve the current Dendrobium breeding programs. Our results also demonstrate that SCoT and TRAP markers are informative and can be used to evaluate genetic relationships between Dendrobium species.


In vitro &in vivo targeting behaviors of biotinylated Pluronic F127/poly(lactic acid) nanoparticles through biotin-avidin interaction.
Biotinylated Pluronic F127/poly(lactic acid) block copolymers (B-F127-PLA) were successfully synthesized previously by our group. In the present study, the release behaviors of paclitaxel-loaded B-F127-PLA nanoparticles and their targeting properties to human ovarian carcinoma cells were investigated. Paclitaxel (pac) loaded in B-F127-PLA nanoparticles shows an initial burst release in the first 6h and followed by a slow release. The in vitro targeting behaviors of B-F127-PLA nanoparticles against human ovarian cancer cells (OVCAR-3, SKOV-3) were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM) technique. Targeting was based on a three-step biotin-avidin targeting approach using biotinylated anti-CA125 antibody specific for the CA-125 antigen that is highly expressed on OVCAR-3 cells but not expressed on SKOV-3 cells. MTT results show that the anticancer effect of paclitaxel in B-F127-PLA nanoparticles over OVCAR-3 cells was stronger than that over SKOV-3 cells, indicating that B-F127-PLA nanoparticles were delivered more effectively to OVCAR-3 cells than to SKOV-3 cells. The targeting behaviors of B-F127-PLA nanoparticles were further confirmed by FM technique. The intracellular distribution of B-F127-PLA nanoparticles was also studied using a triple-labeling method. It was observed that B-F127-PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. The in vivo antitumor efficacy of pac-loaded B-F127-PLA nanoparticles by three-step method as measured by change in tumor volume of OVCAR-3 implanted in Balb/C nude mice was greater than that by one-step method.


Evidence for enhanced telomerase activity in Barrett's esophagus with dysplasia and adenocarcinoma.
Dysplasia and adenocarcinoma developing in Barrett's esophagus (BE) are not always endoscopically identifiable. Molecular markers are needed for early recognition of these focal lesions and to identify patients at increased risk of developing adenocarcinoma. The aim of the current study was to correlate increased telomerase activity (TA) with dysplasia and adenocarcinoma occurring in the setting of BE. Esophageal mucosal biopsies were obtained from patients (N=62) who had pathologically verified BE at esophagogastroduodenoscopy (EGD). Mucosal biopsies were also obtained from the gastric fundus as controls. Based on histopathology, patients were divided into three groups: 1) BE without dysplasia (n=24); 2) BE with dysplasia (both high grade and low grade, n=13); and 3) BE with adenocarcinoma (n=25). TA was measured by a PCR-based assay (TRAPeze® ELISA Telomerase Detection Kit). Statistical analyses were performed using one-way ANOVA and post-hoc Bonferroni testing. TA was significantly higher in biopsies of BE with dyplasia and BE with adenocarcinoma than in BE without dysplasia. Subgroup analyses did not reveal any significant correlations between TA and patient age, length of BE, or presence of gastritis. Telomerase activity in esophageal mucosal biopsies of BE may constitute a useful biomarker for the early detection of esophageal dysplasia and adenocarcinoma.


Evidence for a postnatal elimination of terminal arborizations and synaptic boutons of recurrent motor axon collaterals in the cat.
Triceps surae alpha motoneurons in cats of different postnatal ages were stained intracellularly with horseradish peroxidase (HRP). The recurrent axon collateral trees of the neurons were studied light microscopically. A large reduction of the number of axon collateral end branches and swellings, interpreted as synaptic boutons, was found to occur during the first two weeks of postnatal life.


Evidence for the presence of two 24-h rhythms 180 degrees out of phase in the pineal gland of male Pirbright-White guinea pigs as monitored by counting "synaptic" ribbons and spherules.
Previous studies have shown that the "synaptic" bodies of mammalian pinealocytes are a heterogeneous group of organelles. Whereas "synaptic" ribbons (SR) exhibit a day/night rhythm with small numbers during daytime and high numbers at night, the so-called "synaptic" spherules (SS) show species-specific differences in their rhythmicity. In the present study the numbers of SR and SS were monitored in male guinea pigs over a full 24-h period at 4-hourly intervals (LD 12:12, lights on at 7:00). The results obtained show that the rhythms of SR numbers and SS numbers are out of phase by 180 degrees. SR numbers are small during daytime and high at night, whereas SS numbers are high during daytime and low at night. As there are no indications that SR are transformed into SS and vice versa and as SR and SS lie in different parenchymal areas it is suggested that they characterize different types of pinealocytes with differing rhythmicities. - Serum melatonin levels were low during daytime (30 pg/ml) and increased at night to reach a peak (84 pg/ml) at 24:00 h.


Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways.
Advanced cancer is a multifactorial disease which complicates treatment if the cancer cells have metastasized calling for the targeting of multiple cellular pathways. Gallic acid (GA) is known to possess multiple pharmacological activity including antitumor effects. This study investigated the mechanisms for the anticancer properties of GA on migration and invasion of human osteosarcoma U-2 OS cells. The migration and invasion in U-2 OS cells were determined by a Boyden chamber transwell assay. The expression levels and activities of MMP-2 and MMP-9 were measured by Western blotting, real-time PCR and gelatin zymography assays. All examined proteins levels from Western blotting indicated that GA decreased the protein levels of GRB2, PI3K, AKT/PKB, PKC, p38, ERK1/2, JNK, NF-κB p65 in U-2 OS cells. GA also inhibited the activities of AKT, IKK and PKC by in vitro kinase assay. GA suppressed the migration and invasive ability of U-2 OS cells, and it decreased MMP-2 and MMP-9 protein and mRNA levels and secreted enzyme activities in vitro. These results suggest that potential signaling pathways of GA-inhibited migration and invasion in U-2 OS cells may be due to down-regulation of PKC, inhibition of mitogen-activated protein kinase (MAPK) and PI3K/AKT, resulting in inhibition of MMP-2 and MMP-9 expressions.


Distinct death mechanisms in Drosophila development.
Apoptosis and autophagic cell death occur during Drosophila development, and recent advances in their mechanisms have been made. As in other organisms, apoptosis is executed by caspases. In living cells, caspases are kept in check through a combination of IAP-binding and proteolytic inhibition. Once a cell commits to apoptosis, phagocytes recognize them through the immuno-receptor-like proteins Draper and Simu, and initiate corpse engulfment. Drosophila research has significantly contributed to the idea that autophagy is required for certain forms of cell death, and that caspase function in autophagic cell death depends on cell context. Surprisingly, the cell corpse engulfment receptor Draper also functions in autophagic cell death. These advances facilitate our understanding of the cell death mechanisms in development and disease.


Effects of acute exercise with different modalities on working memory in men with high and low aerobic fitness.
This study aimed to determine the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on working memory in individuals with high and low aerobic fitness. The protocol adopted a between-subjects crossover design. Forty healthy male college students (mean age = 19.59 ± 1.00 years) were assigned to high fitness (n = 20) or low fitness (n = 20) groups based on their estimated maximum oxygen consumption (VO2max) in the 20 m shuttle run test. All participants were instructed to engage in three acute exercise interventions (10 min HIIE, 20 min HIIE, 20 min MICE) and a reading control intervention on separate days in a randomized order. A spatial 2-back task was performed before and after each intervention to assess working memory. Analyses of the 2-back task performance revealed that the working memory of high and low fitness participants benefited from different modalities of acute exercise. Specifically, reaction time in the 2-back task was significantly shorter after 20 min HIIE compared to pre-exercise in high fitness participants, whereas low fitness participants had significantly faster reaction time in the 2-back task after 20 min MICE and 10 min HIIE relative to pre-exercise. The effects of acute aerobic exercise on working memory are modulated by a combination of exercise modality and aerobic fitness. This finding has important implications for providing experimental evidence that participants choose appropriate exercise to undertake based on their level of aerobic fitness to improve cognitive performance.


Indigenous and immigrant populations' use and experience of community pharmacies in New Zealand.
We sought to identify what services indigenous (Maori) and immigrant populations use pharmacies for, and how long pharmacy staff spend interacting with them, as longer interactions are associated with better quality care. We review literature on counseling in pharmacy, and interaction length as an indicator of counseling quality. 1,086 interactions were discretely observed in 36 pharmacies in 5 cities around New Zealand. Maori or Pacific people, along with men, were more likely to treat pharmacies as prescription 'depots', being less likely to buy over-the-counter or pharmacist only medicines (ORs: 0.25-0.72). However, the influence of demographic factors on interaction length was small (|B|s < 7.7 s). The weak effect of ethnicity on interaction length suggests that pharmacies are providing advice of relatively consistent quality to different population groups. Possible barriers to use of pharmacies for primary healthcare, including over-the-counter medicines in Maori and Pacific people are discussed.


Anesthesia machine malfunction simulating spontaneous respiratory effort.
We present a case in which a dip in the capnogram of an anesthetized patient, which may indicate clinical complications such as spontaneous respiratory effort, was caused by a malfunction of the anesthesia delivery system. The rubber diaphragm of the ventilator relief valve was found to be coated with a sticky substance which may have caused adhesion at the valve seat. This adhesion blocked the flow of excess gas to the scavenging system during exhalation. It was demonstrated that a pressure of 5 cm H2O was needed to overcome this adhesion.


Melatonin reduces kainate-induced lipid peroxidation in homogenates of different brain regions.
Melatonin protection against in vitro kainic acid-induced oxidative damage in homogenates from different rat brain regions is shown. Brain-disrupted cell homogenates from cerebral cortex, cerebellum, hippocampus, hypothalamus, and corpus striatum were incubated with kainate (11.7 mM) with or without different concentrations of melatonin (0.1-4 mM). The concentration of malonaldehyde and 4-hydroxyalkenals was measured as an index of lipid peroxidation. Wistar and Sprague-Dawley rats were used. When administered with kainate, melatonin markedly reduced lipid peroxidation in every brain region of both rat strains. The reduction in lipid peroxidation by melatonin was concentration-dependent and varied from 10% to 100%. The protection conferred by melatonin is likely due, at least in part, to its newly discovered, free radical scavenging ability.


Experimental anterior chamber maintenance in active versus passive phacoemulsification fluidics systems.
To evaluate the ability of phacoemulsifiers with active versus passive infusion fluidics control systems to maintain target intraocular pressures (IOPs) under varying flow conditions. Alcon Research, Ltd., Lake Forest, California, USA. Experimental study. An acrylic test chamber was used to model the anterior chamber of the eye. Two passive (gravity-based) systems were tested using bottle heights yielding infusion pressures of 41, 75, and 109 cm of water under zero-flow conditions. One actively controlled system was tested using equivalent target IOPs of 30, 55, and 80 mm Hg. Test chamber IOPs were measured at aspiration flow rates of 15, 30, 45, and 60 cc/min. The measured flow rates were similar between fluidics systems across the range of intended aspiration flow rates. All systems achieved the desired target IOPs under zero-flow conditions. After activation of aspiration flow, however, measured IOPs decreased from target IOPs for the 2 passive systems. Each 15 cc/min increase in the aspiration flow rate produced a pressure drop of 14.0 to 16.2 mm Hg or 9.3 to 14.2 mm Hg, depending on the system. Measured IOPs in the actively controlled system closely matched the targeted IOPs across all tested aspiration flow rates, deviating from targets by no more than 4.3 mm Hg. All phacoemulsification aspiration infusion fluidics systems achieved target IOPs under zero-flow conditions. Only the actively controlled system maintained target IOPs across a range of aspiration flow rates. These experimental findings suggest that anterior chamber stability might be better in the clinical setting using an actively controlled system. Dr. Dimalanta is an employee of Alcon Research, Ltd. Dr. Miller is an investigator and speaker for and a consultant to Alcon Laboratories, Inc. Dr. Nicoli has no financial or proprietary interest in any material or method mentioned.


GDF-15 in tumor-derived exosomes promotes muscle atrophy via Bcl-2/caspase-3 pathway.
Tumor-derived exosomes are emerging mediators of cancer cachexia, a kind of multifactorial syndrome characterized by serious loss of skeletal muscle mass and function. Our previous study had showed that microRNAs in exosomes of C26 colon tumor cells were involved in induction of muscle atrophy. Here, we focus on studying proteins in tumor-derived exosomes which might also contribute to the development of cancer cachexia. Results of comparing the protein profiles of cachexic C26 exosomes and non-cachexic MC38 exosomes suggested that growth differentiation factor 15 (GDF-15) was rich in C26 exosomes. Western blotting analysis confirmed the higher levels of GDF-15 in C26 cells and C26 exosomes, compared with that of MC38 cells. Results of animal study also showed that GDF-15 was rich in tumor tissues, serum exosomes, and gastrocnemius (GA) muscle tissues of C26 tumor-bearing mice. GDF-15 protein could directly induce muscle atrophy of cultured C2C12 myotubes via regulating Bcl-2/caspase-3 pathways. What's more, overexpression of GDF-15 in MC38 cells could increase the potency of MC38 conditioned medium or exosomes in inducing muscle atrophy. Knockdown of GDF-15 in C26 cells decreased the potency of C26 conditioned medium or exosomes in inducing muscle atrophy. These results suggested that GDF-15 in tumor-derived exosomes could contribute to induction of muscle atrophy and also supported the possibility of targeting GDF-15 in treatment of cancer cachexia.


Taking the Leap Toward Cost-Conscious Education in Obstetrics and Gynaecology: A Preliminary Randomized Controlled Trial.
Residents have a professional obligation with respect to the stewardship of health care resources, yet there is a paucity of research on how to improve residents' cost-awareness. Rising health care expenditures highlight a critical need to improve education related to this competency. This study aimed to test if an educational module can teach residents to make cost-conscious decisions and reduce health care spending. All Canadian obstetrics and gynaecology residents in 2017 were eligible to participate in this randomized controlled trial. The study was administered online via REDCap. Interested residents were enrolled, stratified by level of training, and block randomized. Residents completed a survey to determine their management of 4 obstetrical scenarios. The intervention group reviewed an educational module on cost-effective ordering prior to completing the survey; the control group was given the option to review the module afterward. The primary outcome was mean total expenditures, compared between the 2 groups using the t test. Eighty-five residents were enrolled between August and November 2017, and 63 residents from 13 Canadian residency programs completed the study requirements (33 control and 30 intervention). Mean total expenditure was CAD$291.03 (95% CI 259.38-322.68) versus CAD$192.98 (95% CI 170.67-215.29) for the control and intervention groups, respectively. These figures corresponded to a 33.69% or CAD$98.05 reduction in total expenditures (P = 0.0001). This educational module decreased expenditures by Canadian obstetrics and gynaecology residents managing hypothetical obstetrical cases. This introduces a potential curriculum innovation to improve resident education in judicious use of health care resources.


Role of astrocytes in trimethyltin neurotoxicity.
Although the neurotoxicity of trimethyltin (TMT) is well known, mechanisms are still not clear. Glia have been proposed to mediate the toxic action of TMT on nerve cells. Accordingly, the effects of TMT were tested in primary neuronal cultures from rat cerebellum and compared to effects in astrocytes and mixed cultures. Neuronal damage observed following TMT exposure was less in the presence of astrocytes and astrocytes alone were resistant to TMT. Thus, astrocytes have a protective effect against TMT-induced neurotoxicity. TMT caused an oxidative stress in granule cell cultures involving a variety of oxidative species (O2)*-, H2O2, NO), but astrocytes were less sensitive to TMT-induced oxidative species generation. Antioxidants, glutathione and 7-nitroindazole attenuated neuronal cell death induced by TMT. It appears that oxidative stress mediates a large part of the destructive action of TMT in neuronal cultures. The presence of astrocytes appears to modulate TMT-induced oxidative stress so that TMT causes only a small increase in lipid peroxidation in mouse brain after systemic administration. Thus, TMT induces a pronounced oxidative stress in cultured neurons, but when astrocytes are present, oxidative species play a lesser role in the neurotoxic action of TMT.


Admissions to a new burn unit in Gizan, Saudi Arabia.
In an attempt to introduce western treatment principles, Danish chiefs have been in charge of a new Burn Unit in Gizan for the first 2 years and 9 months. We have treated 348 burned patients with a median 16 per cent estimated area of burn (EAB). One-quarter of the patients had more than 25 per cent EAB. Flame burns were the most frequent and females suffered the more severe injury. The mechanisms of burning are discussed.


Comparison of fluorescence polarization immunoassay and HPLC for the determination of theophylline in serum.
Theophylline in serum was measured by fluorescence polarization immunoassay (FPIA) and by high-performance liquid chromatography (HPLC). Within-run precision studies using control samples in the subtherapeutic, therapeutic and toxic concentrations, resulted in coefficients of variation in the range of 2.86-3.12% (FPIA) and 2.1-3.66% (HPLC), respectively. Between-run precision ranged from 2.76-6.2% for FPIA and from 2.51-6.0% for HPLC. The mean recovery for three spiked controls was 98.9% for FPIA and 98.8% for HPLC. Comparison of 60 patients' samples, assayed with both methods, indicated an extremely good analytical correlation (r = 0.990). The FPIA method displayed a slight but consistent positive bias in relation to the concentration of theophylline present in patients sera. Caffeine was found to exhibit a positive bias to 13%, over a caffeine concentration range of 10-40 micrograms/ml. The HPLC method offers an advantage for measurements of both caffeine and theophylline simultaneously. The FPIA offers significant advantages in speed of analysis and turnover-time, while maintaining accuracy and precision compared with those of established HPLC procedures.


Molecular cloning of two gonadotropin receptors in mummichog Fundulus heteroclitus and their gene expression during follicular development and maturation.
Two cDNAs encoding gonadotropin receptors, follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were cloned from mummichog (Fundulus heteroclitus) ovary. Deduced amino acid sequences of the mummichog FSHR (fhFSHR) and LHR (fhLHR) showed high homologies to teleost FSHRs (77-53%) and teleost LHRs (76-62%), respectively. Both the fhFSHR and fhLHR are composed of a typical structural architecture of glycoprotein hormone receptors consisting of the large N-terminal extracellular domain, the transmembrane domain containing seven cell surface membrane-spanning regions, and the intracellular domain. Functional analysis using HEK293 cells stably expressing the fhFSHR or fhLHR demonstrated that both the receptors are specifically activated by mummichog FSH or LH, respectively. Reverse transcription-polymerase chain reaction revealed that both the fhFSHR and fhLHR were expressed in the ovary, testis, and pituitary, and the fhLHR was also expressed in several extra-gonadal tissues. Real-time quantitative-PCR analysis revealed that the fhFSHR gene was abundantly expressed in developing follicles whereas expression of the fhLHR gene markedly increased in follicles of the final maturational stage. These results indicate that gonadotropin stimulation on follicles is regulated by the two distinct pathways via their cognate receptors.


[Diurnal periodicity and the change of the habitat by the larvae of of Potamophylax luctousus (trichoptera)].
Larvae instars of Potamophylax luctuosus build their cases on different material and occur in different habitats. The distribution of the instars was observed in a brook and their daily pattern of locomotory activity was studied in the laboratory. 1. First instars build their cases of plant material. They prefer habitats well exposed to light and current and they are found especially on stones. They show no preference for either diurnal or nocturnal activity and no avoidence of light. 2. Later instars change from plant to stony cases. They are found chiefly in dim habitats, where current is slow. They gradually develop negative phototaxis and nocturnal activity. In constant conditions (DD) no endogenous rhythm has been observed. 3. Late instar larvae have stony cases of fairly uniform small stones. They chiefly are found beneath stones and roots in deep water. Their activity pattern is strictly nocturnal. In constant conditions (DD) they have an endogenous rhythm with a period of about 26-27 hrs. 4. The development of negative phototaxis and nocturnal activity is correlated with the demands of the young larvae for current and food. The endogenous rhythm of activity appears only in the latest instar, during which preparation for pupation occurs. Therefore, it appears that the endogenous rhythm is of great importance for the development of pupa and imago. 5. Daily activity patterns during life history of eight species of Trichoptera are compared.


Projecting the environmental profile of Singapore's landfill activities: Comparisons of present and future scenarios based on LCA.
This article aims to generate the environmental profile of Singapore's Semakau landfill by comparing three different operational options associated with the life cycle stages of landfilling activities, against a 'business as usual' scenario. Before life cycle assessment or LCA is used to quantify the potential impacts from landfilling activities, an attempt to incorporate localized and empirical information into the amounts of ash and MSW sent to the landfill was made. A linear regression representation of the relationship between the mass of waste disposed and the mass of incineration ash generated was modeled from waste statistics between years 2004 and 2009. Next, the mass of individual MSW components was projected from 2010 to 2030. The LCA results highlighted that in a 'business as usual' scenario the normalized total impacts of global warming, acidification and human toxicity increased by about 2% annually from 2011 to 2030. By replacing the 8000-tonne barge with a 10000-tonne coastal bulk carrier or freighter (in scenario 2) a grand total reduction of 48% of both global warming potential and acidification can be realized by year 2030. Scenario 3 explored the importance of having a Waste Water Treatment Plant in place to reduce human toxicity levels - however, the overall long-term benefits were not as significant as scenario 2. It is shown in scenario 4 that the option of increased recycling championed over all other three scenarios in the long run, resulting in a total 58% reduction in year 2030 for the total normalized results. A separate comparison of scenarios 1-4 is also carried out for energy utilization and land use in terms of volume of waste occupied. Along with the predicted reductions in environmental burdens, an additional bonus is found in the expanded lifespan of Semakau landfill from year 2032 (base case) to year 2039. Model limitations and suggestions for improvements were also discussed.


Sarcocystis neurona reacting antibodies in Missouri feral domestic cats (Felis domesticus) and their role as an intermediate host.
Sarcocystis neurona is the parasite associated with equine protozoal myeloencephalitis (EPM). Recently, cats (Felis domesticus) have been implicated as a potential intermediate host in the life cycle of S. neurona. This study was initiated to determine whether cats have antibodies that react to S. neurona antigens similar to antibodies from horses with EPM, and to evaluate the role of cats as intermediate hosts in the parasite's life cycle. Nine feral cats were used for analysis. Only one had antibodies reacting to S. neurona antigens. Muscle tissue from this cat, with detectable sarcocysts in the tongue, was fed to an opossum (Didelphis virginiana). The opossum shed sporocysts, which were then fed to gamma-interferon receptor knockout mice. Histopathology, immunohistochemistry, parasite isolation and molecular analysis were used to examine the pathology and associated parasites in the mice. The study suggests that the domestic cat can serve as an intermediate host to S. neurona or a S. neurona-like organsim.


Isolation and propagation of HIV-1 on peripheral blood mononuclear cells.
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by a gradual loss of CD4+ T cells and T-cell function and an ongoing high level of virus replication. The high replication rate and the error-prone nature of HIV-1 reverse transcriptase create a diverse viral quasispecies throughout infection. To study biological properties of HIV-1 quasispecies in relation to the clinical course of infection, the in vitro preservation of phenotypical characteristics of the virus is essential. Here, we describe the method for bulk isolation of the HIV-1 quasispecies and a limiting dilution virus isolation protocol by which single coexisting HIV-1 variants can be obtained using peripheral blood mononuclear cells from a healthy donor as target cells. In addition, methods for propagation and titration of HIV-1 are provided.


Effect of Transmembrane Electric Field on GM1 Containing DMPC-Cholesterol Monolayer: A Computational Study.
Transmembrane electric potentials and membrane curvature have always provided pathways to mediate different cellular processes. We present results of molecular dynamics (MD) simulations of lipid monolayer composed of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol (CHOL) under a transverse electric field to monitor the effect of electric field on membrane containing ganglioside monosialo 1 (GM1). Four systems were studied with membrane monolayer in the presence and absence of GM1 with and without applying electric field along the normal of the monolayer. The applied transmembrane electric field was 0.4 mV/Å which corresponds to the action potential of animal cell. Our results indicate that the electric field induces a considerable lateral stress on the monolayer in the presence of GM1, which is evident from the lateral pressure profiles. It was found that due to the application of electric field major perturbation was caused to the system containing GM1, manifested by the bending of the monolayer. We believe this study provides correlation between electric field and spontaneous membrane bending, specially based on the membrane composition. The consequences of these MD simulations provide considerable insights to different biological phenomenon and lipid membrane models.


Elevation of plasma prolactin concentrations by intravenous SCH 23390 and SKF 38393 in conscious rats.
The effect of the selective dopamine-1 (D-1) antagonist, SCH 23390 and the selective D-1 agonist, SKF 38393 on plasma prolactin levels was investigated in conscious, freely moving male rats. Plasma prolactin was markedly increased by the intravenous injection of either SCH 23390 or SKF 38393 in a dose-related fashion. The maximal prolactin response was observed 15 min after drug injection. The d-isomer of SKF 38393 was significantly more potent than the l-isomer. In urethane-anesthetized rats, the two drugs produced similar effects on prolactin as those in the conscious animal preparation. Both SCH 23390 and SKF 38393 potentiated the sulpiride-induced prolactin elevation. These observations suggest that pharmacologic stimulation, or blockade of D-1 receptors in the living animal, can mimic the action of a D2 antagonist at the anterior pituitary lactotroph. We have speculated on the possible mechanisms in pituitary and higher in the central nervous system which might be responsible for the prolactin changes caused by either SCH 23390 or SKF 38393.


Nitrification in a vertically moving biofilm system.
A laboratory continuous feed biofilm reactor, comprising a bulk fluid reactor, a biofilm plastic module, a feed tank, and pneumatic devices and controls, was operated for a total period of 257 days, including seeding time, to treat domestic-strength synthetic wastewater under increasing ammonium nitrogen (NH(4)(+)--N) loading rates, ranging from 0.17+/-0.01 (0.71+/-0.06 gm(-2)d(-1)) to 0.70+/-0.02 kgm(-3)d(-1) (2.9+/-0.1 gm(-2)d(-1)). The biofilm plastic module was moved vertically in and out of the wastewater in continuous cycles. The maximum NH(4)(+)-N removal rate was reached during the maximum loading phase, when a NH(4)(+)--N loading rate of 0.70+/-0.02 kgm(-3)d(-1) (2.9+/-0.1 gm(-2)d(-1)) was applied to the system. During this loading period, the average NH(4)(+)--N removal rate was 0.30+/-0.10 kgm(-3)d(-1) (1.30+/-0.40 gm(-2)d(-1)).


Selenate triggers diverse oxidative responses in Astragalus species with diverse selenium tolerance and hyperaccumulation capacity.
Selenium (Se) hyperaccumulators are capable of uptake and tolerate high Se dosages. Excess Se-induced oxidative responses were compared in Astragalus bisulcatus and Astragalus cicer. Plants were grown on media supplemented with 0, 25 or 75 μM selenate for 14 days. Both A. bisulcatus and A. cicer accumulated >2000 μg/g dry weight Se to the shoot but the translocation factors of A. cicer were below 1 suggesting its non hyperaccumulator nature. A. cicer showed Se sensitivity indicated by reduced seedling fresh weight, root growth and root apical meristem viability, altered element homeostasis in the presence of Se. In Se-exposed A. bisulcatus, less toxic organic Se forms (mainly MetSeCys, γ-Glu-MetSeCys, and a selenosugar) dominated, while these were absent from A. cicer suggesting that the majority of the accumulated Se may be present as inorganic forms. The glutathione-dependent processes were more affected, while ascorbate levels were not notably influenced by Se in either species. Exogenous Se triggered more intense accumulation of malondialdehyde in the sensitive A. cicer compared with the tolerant A. bisulcatus. The extent of protein carbonylation in the roots of the 75 μM Se-exposed A. cicer exceeded that of A. bisulcatus indicating a correlation between selenate sensitivity and the degree of protein carbonylation. Overall, our results reveal connection between oxidative processes and Se sensitivity/tolerance/hyperaccumulation and contribute to the understanding of the molecular responses to excess Se.


The distribution of acidic coomassie blue-stained proteins from uninvolved human liver, hepatoma, normal colon, primary colon cancer, and colon metastases to the liver, determined by two-dimensional protein electrophoresis.
The distribution of Coomassie blue-stained proteins from uninvolved regions of 4 human livers, from 1 hepatocellular carcinoma, and from 4 samples each of uninvolved colon, primary adenocarcinoma of the colon, and colon cancer metastatic to the liver was analyzed by two-dimensional protein electrophoresis. From a comparison of acidic proteins between pI 3.5 and 6.5, we conclude (1) that the majority (66 of 82) of denoted acidic proteins from 4 normal liver samples were represented in the hepatocellular carcinoma. Fifty-one of 58 proteins denoted in the 4 colon samples were detected in each of the 4 primary colon cancers; (2) that the "normograms" of proteins from normal colon and normal liver differed in many details, and their dissimilar patterns identified the source of the sample; (3) that hepatoma and primary adenocarcinoma of the colon were easily distinguished by their distribution of proteins; (4) that colon cancer metastatic to the liver contained a majority (50/58) of acidic proteins enumerated in primary colon cancer. These results indicate that uninvolved liver and colon and their primary or secondary cancers can be identified by their distribution of electrophoresed acidic proteins.


Microleakage of indirect composite inlays.
The purpose of this in vitro study was to evaluate the microleakage of indirect composite inlays and to compare leakage of inlays with directly placed composite restorations. Standardized MOD preparations were cut in 50 extracted human molars. One gingival margin was placed in enamel above the CEJ, and the other was placed in dentin below the CEJ. Two groups of teeth were directly filled with composites (P-30 and Heliomolar) after being etched, and dentin bonding agents were applied. Two groups of teeth were restored with composite inlays that were fabricated on stone dies. The inlays were made and luted with the same two composites. The last group of teeth was restored with Heliomolar inlays luted with Dual cement. The specimens were thermocycled 300 times between 5 and 50 degrees C. Microleakage was evaluated by use of the silver-nitrate staining technique. The depth of leakage was measured microscopically after the teeth were sectioned. Both direct restorations and inlays showed substantial leakage at gingival-dentin margins; however, there was only superficial leakage at enamel margins. P-30 inlays and Heliomolar inlays cemented with Dual leaked less than direct restorations at the gingival-dentin margins. There was no difference in leakage of enamel margins of inlays and direct restorations, except that direct Heliomolar restorations leaked more than the others. There was no difference in leakage between Heliomolar restorations luted with light-cured or dual-cured cement.


Biaxial mechanical properties of the bronchial tree: Characterization of elasticity, extensibility, and energetics, including the effect of strain rate and preconditioning.
Distal airways commonly obstruct in lung disease and despite their importance, their mechanical properties are vastly underexplored. The lack of bronchial experiments restricts current airway models to either assume rigid structures, or extrapolate the material properties of the trachea to represent the small airways. Furthermore, past works are exclusively limited to uniaxial testing; investigating the multidirectional tensile loads of both the proximal and distal pulmonary airways is long overdue. Here we present comprehensive mechanical and viscoelastic properties of the porcine airway tree, including the trachea, trachealis muscle, large bronchi, and small bronchi, via measures of elasticity, extensibility, and energetics to explore regional and directional dependencies, cross-examining strain rate and preconditioning effects using planar equibiaxial tensile tests for the first time. We find bronchial regions are notably heterogeneous, where the trachea exhibits greater stiffness, energy loss, and preconditioning sensitivity than the smaller airways. Interestingly, the trachealis muscle is similar to the distal bronchi, despite being anatomically located adjacent to the proximal ring. Tissues are anisotropic and axially stiffer under initial loading, losing more energy with greater stress relaxation circumferentially. Strain rate dependency is also noted, where tissues are more energetically efficient at the faster strain rate, likely attributable to the microstructure. Findings highlight assumptions of homogeneity and isotropy are inadequate, and enable the improvement of aerosol flow and dynamic airway deformation computational predictive models. These results provide much needed fundamental material properties for future explorations contrasting healthy versus diseased pulmonary airway mechanics to better understand the relationship between structure and lung function. STATEMENT OF SIGNIFICANCE: We present comprehensive multiaxial mechanical tensile experiments of the proximal and distal airways via measures of maximum stress, initial and ultimate moduli, strain and stress transitions, hysteresis, energy loss, and stress relaxation, and further assess preconditioning and strain rate dependencies to examine the relationship between lung function and structure. The mechanical response of the bronchial tree demonstrates significant anisotropy and heterogeneity, even within the tracheal ring, and emphasizes that contrary to past studies, the behavior of the proximal airways cannot be extended to distal bronchial tree analyses. Establishing these material properties is critical to advancing our understanding of airway function and in developing accurate computational simulations to help diagnose and monitor pulmonary diseases.


Room-temperature electrical control of polarization and emission angle in a cavity-integrated 2D pulsed LED.
Devices based on two-dimensional (2D) semiconductors hold promise for the realization of compact and versatile on-chip interconnects between electrical and optical signals. Although light emitting diodes (LEDs) are fundamental building blocks for integrated photonics, the fabrication of light sources made of bulk materials on complementary metal-oxide-semiconductor (CMOS) circuits is challenging. While LEDs based on van der Waals heterostructures have been realized, the control of the emission properties necessary for information processing remains limited. Here, we show room-temperature electrical control of the location, directionality and polarization of light emitted from a 2D LED operating at MHz frequencies. We integrate the LED in a planar cavity to couple the polariton emission angle and polarization to the in-plane exciton momentum, controlled by a lateral voltage. These findings demonstrate the potential of TMDCs as fast, compact and tunable light sources, promising for the realization of electrically driven polariton lasers.


Precise membrane separation of nanoparticles using a microporous polymer containing radially π-conjugated molecular carbocycles.
Herein, we report the synthesis of a novel porous polymer, PS2, containing radially π-conjugated carbocycles and a linear phenylene backbone. The PS2-based membrane has a distinct small size cutoff (ca. 2.6 nm) and a major size at ∼1.5 nm for the size-selective separation of nanoparticles.


Germline-encoded specificities and the predictability of the B cell response.
Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors, the precursors to antibodies, are encoded by particular immunoglobulin alleles. This raises the possibility that the presence of particular germline alleles in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline alleles' propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first investigate these scenarios in simulations: when germline-encoded fitness differences are large relative to the rate and effect size variation of somatic mutations, the same germline alleles persistently dominate the response of different individuals. In contrast, if germline-encoded advantages can be easily overcome by subsequent mutations, allele usage becomes increasingly divergent over time, a pattern we then observe in mice experimentally infected with influenza virus. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest that although germline-encoded specificities can lead to similar immune responses between individuals, diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination.


Erratum: Prevalence of and risk factors for equine glandular and squamous gastric disease in polo horses.
[This corrects the article on p. 880 in vol. 59, PMID: 30104780.].


[Characterization of the teaching in Hansen's disease in the undergraduate nursing education in the State of São Paulo].
The study describes the situation of the hanseniasis teaching in the undergraduated nursing courses. In the analysis based on data taken from five schools of the state of São Paulo, Brazil, a heterogeneity of procedures became evident in the disease teaching, related to the schedule used, to the local of practical training activities, as well as to specific subjects on hanseniasis.


[Cicatricial pemphigoid, mucous membrane pemphigoid].
Mucous membrane pemphigoid belongs to the family of sub-epidermal bullous diseases and is clinically characterized by mucosal involvement leading to fibrosis and scarring. Cutaneous involvement is unfrequent and oral mucosa and conjunctivas are the most frequently involves mucosa. Treatment relies on anti-inflammatory and immunosuppressive drugs. The main goal is the limitation of the fibrosing potential of the autoimmune deposits within various mucous membranes.


Performance and short-term outcomes of three different transcatheter aortic valve replacement devices in patients with aortic stenosis: A single-center experience.
Data on whether different transcatheter aortic valve replacement (TAVR) devices and delivery approaches can achieve equally favorable outcomes when performed by a single heart team are scarce. We sought to compare the performance and short-term outcomes of three different TAVR devices-self-expanding Medtronic CoreValve (MCV), mechanically expanded Lotus valve, and balloon-expandable Edwards SAPIEN XT (SXT)-for the treatment of severe aortic stenosis (AS) in a single large-volume center in Taiwan. We retrospectively reviewed consecutive patients who underwent TAVR for the treatment of severe AS. Clinical outcomes were reported following Valve Academic Research Consortium 2 (VARC-2) criteria. The composite primary endpoint was combined all-cause mortality, myocardial infarction (MI), or disabling stroke within 180 days. A total of 231 patients (MCV n=112, Lotus n=18, and SXT n=101) were included. The device and procedural success rates were similar among all three TAVR devices. At 30 days, there was no significant difference in all-cause mortality, cardiovascular mortality, periprocedural MI, stroke, major vascular complications, life-threatening bleeding, acute kidney injury (AKI, stage 2/3), or VARC-2 composite early safety endpoints. There was no difference among groups in the rate of primary endpoint within 180 days. Lack of procedural success, presence of acute coronary occlusion during TAVR, and presence of AKI (stage 3) after TAVR were independent predictors of adverse outcomes. TAVR using MCV, Lotus, or SXT was associated with similar 30- and 180-day clinical outcomes. The presence of periprocedural complications was one of the main determinants of short-term adverse outcomes.


Ethanol Extract of Cissus quadrangularis Enhances Osteoblast Differentiation and Mineralization of Murine Pre-Osteoblastic MC3T3-E1 Cells.
Traditional medicinal literature and previous studies have reported the possible role of Cissus quadrangularis (CQ) as an anti-osteoporotic agent. This study examines the effectiveness of CQ in promoting osteoblast differentiation of the murine pre-osteoblast cell line, MC3T3-E1. Ethanolic extract of CQ (CQ-E) was found to affect growth kinetics of MC3T3-E1 cells in a dosage-dependent manner. High concentrations of CQ-E (more than 10 μg/ml) have particularly adverse effects, while lower concentrations of 0.1 and 1 µg/ml were non-toxic and did not affect cell viability. Notably, cell proliferation was significantly increased at the lower concentrations of CQ-E. CQ-E treatment also augmented osteoblast differentiation, as reflected by a substantial increase in expression of the early osteoblast marker ALP activity, and at later stage, by mineralization of extracellular matrix compared to the control group. These findings suggest dose-dependent effect of CQ-E with lower concentrations exhibiting anabolic and osteogenic properties. J. Cell. Physiol. 232: 540-547, 2017. © 2016 Wiley Periodicals, Inc.


Harsh parenting and child aggression: Child moral disengagement as the mediator and negative parental attribution as the moderator.
As the negative outcomes of harsh parenting for child development have been gradually revealed, researchers become increasingly interested in the mechanisms through which harsh parenting affects child development. This study aimed to explore the mediating role of child moral disengagement and the moderating role of negative parental attribution in the relation of harsh parenting to child aggression. A sample of 397 Chinese adolescents aged from 12 to 16 years (227 boys and 170 girls, Mage = 13.98) with their parents were recruited as participants from two public schools situated in rural areas of Shandong province in China. Data were gathered from parents reporting on their harsh parenting and negative parental attribution, adolescents reporting on their moral disengagement, and peers nominating out aggressive children. Results indicated that harsh parenting was both directly and indirectly associated with adolescent aggression via adolescent moral disengagement. Negative parental attribution was found to moderate the indirect relation of harsh parenting to adolescent aggression via moral disengagement. Specifically, harsh parenting was only significantly associated with moral disengagement for adolescents with high levels of moral disengagement was more likely to induce aggression among adolescents with high levels of negative parental attribution (bsimple = of harsh parenting to adolescent aggression, adolescent moral disengagement could mediate the association between harsh parenting and aggressive behaviors for adolescents with high levels of negative parental attribution.


Utility of Carbon Dioxide Venography and Intraprocedural CT for Adrenal Venous Sampling in Patients with an Allergy to Iodinated Contrast Media.
To assess the diagnostic performance of carbon dioxide (CO2) and intraprocedural unenhanced computed tomography (CT) for adrenal venous sampling (AVS) (CO2-intraprocedural unenhanced CT-AVS) in patients with primary aldosteronism (PA) and a history of iodine contrast medium allergy. CO2-intraprocedural unenhanced CT-AVS was performed in 18 patients with iodine contrast media allergies at the authors' hospital between December 2015 and January 2021. CT and noncontrast magnetic resonance angiography were used to evaluate the preoperative adrenal vein anatomy. CO2 venography was performed to confirm adrenal vein catheterization. Additionally, intraprocedural unenhanced CT was also performed to confirm catheter position in the right adrenal gland. In all cases in which CO2-intraprocedural unenhanced CT-AVS was performed, the right and left adrenal veins were catheterized appropriately, leading to a localized diagnosis. Catheterization of the left adrenal vein was confirmed using CO2 venography in all cases. In 7 of the 18 cases, CO2 venography demonstrated selection of the right adrenal vein. In 15 of 18 cases, intraprocedural unenhanced CT demonstrated selection of the right adrenal vein. CO2-intraprocedural unenhanced CT-AVS demonstrated the same diagnostic ability for PA localization as conventional AVS with iodine contrast media. The proposed method is clinically feasible for AVS, in which iodine contrast media use is restricted.


CT angiography with multidetector-row helical CT in spinal arteriovenous malformation.
We performed intravenous CT angiography using multidetector-row helical computed tomography (MDCT) in a 63-year-old man with spinal arteriovenous malformation (AVM). The CT angiography demonstrated feeding arteries, varix-like structure, draining veins and their relationship to the spinal cord. Although selective angiography is essential in planning treatment for spinal AVMs as well as in establishing the diagnosis of the disease, CT angiography can be a good supplementary technique for visualizing precise location of abnormal vessels in a certain case of spinal AVM.


Inhibition of gastric pepsin secretion by peripherally or centrally injected interleukin-1 in rats.
The present study was carried out to investigate the effects of Interleukin-1 (IL-1) on gastric pepsin secretion in conscious pylorus-ligated rats. The intraperitoneal (ip) injection of IL-1 resulted in a dose-related inhibition of gastric pepsin output. The intracerebroventricular (icv) injection of IL-1 similarly reduced pepsin secretion at 100 times smaller doses than ip IL-1, suggesting that this inhibitory action of IL-1 is mediated by the central nervous system (CNS). In addition, it was found that the antisecretory action of IL-1, both peripherally and centrally administered, lasted throughout the periods observed (2 hr through 8 hr after injection). These results strongly indicate that IL-1 is involved in the CNS regulation of gastric secretion, especially under certain pathophysiological conditions which activate the immune system to release various cytokines including IL-1.


Regulation of isoflavone production in hydroponically grown Pueraria montana (kudzu) by cork pieces, XAD-4, and methyl jasmonate.
A mini-hydroponic growing system was employed for seedlings of kudzu vine (Pueraria montana) and contents of isoflavones (daidzein, genistein, daidzin, genistin, and puerarin) from shoot and root parts of seedlings were analyzed quantitatively. In addition, exogenous cork pieces, polymeric adsorbent, XAD-4, and universal elicitor, methyl jasmonate (MeJA), were used to regulate the production of these isoflavones. It was shown that cork pieces up-regulate the production of daidzein and genistein up to seven- and eight-fold greater than the levels obtained for control roots. In contrast, levels of glucosyl conjugates, daidzin and genistin, decrease up to five- and eight-fold, respectively. Cork treatment also induces the excretion of the root isoflavone constituents into the growth medium. Minimal levels of isoflavones are absorbed by the cork pieces. XAD-4 stimulates the production of glucosyl conjugates, daidzin and genistin, in root parts about 1.5-fold greater than that obtained in control roots. These are the highest amounts of daidzin and genistin that are observed (5.101 and 6.759 mg g(-1) dry weight, respectively). In contrast to these two adsorbents, MeJA increases the accumulation of isoflavones in shoot rather than in root parts of seedlings, about three- to four-fold over control levels, with the exception of genistein. These studies reveal new observations on the regulation of isoflavone production in hydroponically grown Pueraria montana plants by two adsorbents (cork pieces and XAD-4) and MeJA elicitor.


Engineering a "dual-key-and-lock" ratiometric fluorescent nanoprobe for real-time reporting the freshness and quality of meat.
Accurate and real-time reporting the freshness and quality of meat has far-reaching implications for safeguarding food safety and public health. Owing to the significant indicator role of H2S in meat spoilage, we here designed a ''dual-key-and-lock'' kind of H+-powered H2S-responsive ratiometric fluorescent nanoprobe BODIPY/Cy7Cl@HyNPs for precise and real-time evaluating the meat freshness. After incubation with spoilt meat, BODIPY/Cy7Cl@HyNPs was simultaneously initiated by the abnormal H+ and H2S acted as "dual-keys". As a result, the fluorescence emission of BODIPY/Cy7Cl@HyNPs at ∼ 688 nm was enhanced, and the other emission at ∼ 818 nm was quenched, thereby yielding a typical H+-powered ratiometric fluorescence response toward H2S in meat. In addition, we also successfully exploited BODIPY/Cy7Cl@HyNPs to achieve the real-time monitoring of the meat freshness during storage by measuring the changes of fluorescence signals and solution color.


Cognitive load mitigates the executive but not the arousal vigilance decrement.
Previous research has shown opposite effects of dual tasking on the vigilance decrement phenomenon. We examined the executive (i.e., detecting infrequent critical signals) and arousal (i.e., sustaining a fast reaction to stimuli without much control on responses) vigilance decrements as a function of task load. Ninety-six participants performed either a single signal-detection (i.e., executive vigilance) task, a single reaction time (i.e., arousal vigilance) task, or a dual vigilance task with the same stimuli and procedure. All participants self-reported their fatigue' state along the session. Exploratory analyses included data from a previous study with a triple task condition. Task load significantly modulated the executive but not the arousal vigilance decrement. Interestingly, the largest increase in mental fatigue was observed in the single executive vigilance task condition. We discuss limitations of classic vigilance theories to account for the vigilance decrement and changes in mental fatigue as a function of task load.


"It's the skin you're in": African-American women talk about their experiences of racism. an exploratory study to develop measures of racism for birth outcome studies.
Stress due to experiences of racism could contribute to African-American women's adverse birth outcomes, but systematic efforts to measure relevant experiences among childbearing women have been limited. We explored the racism experiences of childbearing African-American women to inform subsequent development of improved measures for birth outcomes research. Six focus groups were conducted with a total of 40 socioeconomically diverse African-American women of childbearing age in four northern California cities. Women reported experiencing racism (1) throughout the lifecourse, with childhood experiences seeming particularly salient and to have especially enduring effects (2) directly and vicariously, particularly in relation to their children; (3) in interpersonal, institutional, and internalized forms; (4) across different life domains; (5) with active and passive responses; and (6) with pervasive vigilance, anticipating threats to themselves and their children. This exploratory study's findings support the need for measures reflecting the complexity of childbearing African-American women's racism experiences. In addition to discrete, interpersonal experiences across multiple domains and active/passive responses, which have been measured, birth outcomes research should also measure women's childhood experiences and their potentially enduring impact, perceptions of institutionalized racism and internalized negative stereotypes, vicarious experiences related to their children, vigilance in anticipating future racism events, as well as the pervasiveness and chronicity of racism exposure, all of which could be sources of ongoing stress with potentially serious implications for birth outcomes. Measures of racism addressing these issues should be developed and formally tested.


Long-term outcomes of IgA nephropathy patients with less than 25% crescents and mild proteinuria.
Whether immunosuppressive therapy in IgA nephropathy (IgAN) patients with less than 25% crescents (C1) and mild proteinuria can improve the renal outcome is still unclear. We recruited 140 IgAN patients with C1 and proteinuria < 1 g/24 h who received supportive care (n = 52) or steroid-based immunosuppressive therapy (n = 88) in Xijing Hospital from July 2008 to December 2016. The primary outcome was the rate of renal function decline. The median of proteinuria was 575.5 mg/24 h, the fraction of crescents was 7% (5%, 12%) and follow-up time was 69.1 months. The rate of renal function decline [0.5 (- 1.5, 3.2) vs - 0.7 (- 3.5, 0.5) ml/min per 1.73 m2 per year; P = 0.01] was slower in steroid-based immunosuppressive therapy group than supportive care group. Multivariate linear regression analyses showed steroid-based immunosuppressive therapy significantly slowed down the rate of renal function decline (β = - 0.220, 95% CI - 3.804 to - 0.449, P = 0.013) after adjusting age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, the fraction of crescents and RASB. In the matched cohort, the rate of renal function decline was also slower in steroid-based immunosuppressive therapy group. The incidence of adverse events was similar between the two groups. Steroid-based immunosuppressive therapy may slow down the rate of renal function decline of IgAN patients with C1 and proteinuria ≤ 1 g/24 h.


Optimal hematocrit in patients on dialysis therapy.
Although recombinant erythropoietin (rHuEPO) has been available for use in dialysis patients since 1989, there is little information available on the optimal hematocrit to target in this patient population. The optimal hematocrit is the value that supplies the amount of oxygen to specific tissues and organs that maximizes the efficiency and effectiveness of organ function. Very few prospective studies have been published on this issue, and the retrospective review of clinical practice data is inadequate because of the small number of patients maintained with a hematocrit greater than 36%. Several recent abstracts shed light on this issue, however, and additional publications are likely soon. The available data indicate that brain and cognitive function are better at a normal hematocrit compared with the currently achieved values (31% to 32%). In addition, quality of life and exercise capacity improve as hematocrit is normalized. The AMGEN Normal Hematocrit Cardiac Trial (NHCT), studying the effects of normalizing the hematocrit in dialysis patients with heart disease, does not clearly show the benefit or harm of a normal hematocrit in this patient setting, although within both study groups (hematocrit of 30% v 42%), survival was better in patients with higher hematocrits. The challenge for clinicians is to determine the optimal hematocrit for a specific patient that maximizes organ function but does not cause adverse effects. Over the next few years, several studies should be published based on current abstracts, and if the results remain as reported, the evidence will be accumulating that normal hematocrits are beneficial in end-stage renal disease (ESRD) patients.


Early life circumstances and atopic disorders in childhood.
The prevalence of childhood atopic disorders has risen dramatically in the last decades of the past century. Risk factors for the development of these disorders have been studied extensively. This review focuses on the role of early life risk factors such as pre-natal development, perinatal circumstances, birth order and childhood vaccinations.


Electrolysis with diamond anodes of the effluents of a combined soil washing - ZVI dechlorination process.
In this work, a new soil washing process in which Soil-Liquid extraction technology is enhanced by adding iron particles (zero valent iron nanoparticles or granules) was investigated to remove clopyralid from spiked soils. This novel approach can be efficiently used to extract chlorinated hydrocarbons from soil and aims to obtain soil-washing wastes with low content of hazardous chlorinated species. The iron particles used were subsequently removed from the treated soil using magnetic fields. Then, the complete mineralization of the produced soil washing effluents was successfully achieved by applying anodic oxidation with diamond anodes in an electrochemical flow cell. Results demonstrated that, opposite to what it was initially expected, no improvements in the efficiency of the electrochemical process were observed by adding iron particles during the soil washing. This behavior is explained in terms of the lower electrochemical reactivity of the dechlorinated derivatives produced. Although results are not as promising as initially expected, it does not mean a completely negative outcome for the use of ZVI during washing, because the hazardousness of the pollutants is rapidly decreased in the initial stages of the soil-washing, opening the possibility for the combination of this technology with other processes, such as biological treatment.


Enhanced IgG1 -mediated antibody response towards thymus-dependent immunization in CXCR1-deficient mice.
Chemokine receptors and their corresponding ligands are key players of immunity by regulation of immune cell differentiation and migration. CXCR1 is a high-affinity receptor for CXCL8. Differential expression of CXCR1 is associated with a variety of human pathologies including cancer and inflammatory diseases. While various studies have highlighted the importance of CXCR1-mediated CXCL8-sensing for neutrophil trafficking and function, its role in B-cell responses remains unsolved. Therefore, our aim was to investigate innate and adaptive antibody responses in CXCR1-deficient mice. Cell populations of the spleen and the peritoneal cavity were identified and quantified via flow cytometry. To investigate thymus-independent (TI) and thymus-dependent (TD) antibody responses, mice were immunized intraperitoneally with TNP-Ficoll, Pneumovax23, and TNP-Chicken Gamma Globulin. Mice were bled before as well as 7 and 14 days after vaccination to collect serum. Serum antibody levels overtime were analyzed according to their specificity by enzyme-linked immunosorbent assay. B-1 cell functionality was examined by IL-5/IL-5Rα-dependent stimulation of peritoneal and splenic cells in vitro. To analyze CXCR1/2-expression, CD19+ splenocytes were enriched by magnetic-activated cell sorting before isolation of total RNA contents, followed by reverse transcription and real-time polymerase chain reaction. The distribution of natural B-1 cell populations was disturbed in the absence of CXCR1, while their responsiveness towards TI antigens and in vitro stimulation remained functional. Besides, CXCR1-deficiency was accompanied by increased frequencies of follicular B-2 cells in the spleen. Interestingly, these mice produced elevated levels of antigen-specific IgG1 upon TD immunization and harbored a significantly enlarged proportion of CXCR5-expressing T helper (H) cells. CXCR1-expression was detectable in CD19+ splenocytes derived from wild-type, but not CXCR1-deficient mice. Our data demonstrate a previously unknown relevance of CXCR1 for the production of specific IgG1 in response to vaccination. These findings identify CXCR1 as a promising candidate for future studies on the regulation of adaptive antibody responses.


Direct relationship between elevated free testosterone and insulin resistance in hyperprolactinemic women.
Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or insulin resistance. However, little is known about the association of hyperandrogenemia and insulin resistance in these women. To investigate whether hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women, and to assess the relationship between them, we measured basal androgen level and both glucose and insulin levels after oral glucose administration in 20 hyperprolactinemic women and 7 female control subjects. Free testosterone level was higher and estradiol level lower in hyperprolactinemic women than in control subjects (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total testosterone levels were similar (p > 0.05). Both fasting glucose and insulin levels didn't differ in the two groups (p > 0.05). However, both serum glucose and insulin levels, after a 75 g glucose load, were significantly increased in hyperprolactinemic women, (p = 0.001, p < 0.001, respectively). In simple linear regression analysis in hyperprolactinemic women, only free testosterone level had a positive correlation with the incremental area under the insulin curve (insulin-IAU) (r = 0.47, p < 0.05). In multiple stepwise regression analysis, free testosterone level, mean blood pressure and DHEAS level were associated significantly with insulin-IAU (beta = 0.98, p < 0.0001; beta = 0.58, p = 0.002; beta = -0.67, p < 0.003, respectively). These results suggest that insulin resistance is closely related to elevated free testosterone level in hyperprolactinemic women.